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large_stringclasses
414 values
reaction_id
large_stringlengths
36
36
reaction_smiles
large_stringlengths
4
873
rxn_insight_reaction
large_stringlengths
19
1.07k
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large_stringlengths
14
3.37k
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large_stringlengths
1
581
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large_stringlengths
1
433
reagent_smiles
large_stringclasses
634 values
catalyst_smiles
large_stringlengths
1
683
solvent_smiles
large_stringlengths
1
245
rxn_insight_class
large_stringclasses
11 values
rxn_insight_name
large_stringclasses
346 values
rxn_insight_tag
large_stringlengths
64
64
rxn_insight_tag2
large_stringlengths
64
64
rxn_insight_scaffold
large_stringlengths
5
288
rxn_insight_template
large_stringlengths
24
2.64k
yield_percent
float64
-0.8
90,205,160,000B
yield_measurements
large_stringlengths
2
864
temperature_value
float64
-230
30.1k
temperature_units
large_stringclasses
3 values
reaction_time_value
float64
0
4k
time_units
large_stringclasses
4 values
procedure_details
large_stringlengths
1
23.6k
reference
large_stringclasses
96 values
doi
large_stringclasses
19 values
functional_groups_reactants
large_stringlengths
3
716
functional_groups_products
large_stringlengths
3
539
participating_rings_reactants
large_stringlengths
5
293
participating_rings_products
large_stringlengths
5
271
all_rings_products
large_stringlengths
5
271
byproduct_smiles
large_stringclasses
176 values
agent_smiles
large_stringlengths
1
712
temperature_c
float64
-230
30.1k
reaction_time_hours
float64
0
2.16k
reaction_smiles_with_agents
large_stringlengths
4
882
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-425b0d7fa4994b22b3823527f754cbae
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3F)C[C@@H]2C)cc1>>COc1ccc(C(=O)N2c3ccccc3[C@H](N)C[C@@H]2C)cc1
ClC1=CC(=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C)F.FC1=CC=C(C(=O)Cl)C=C1>>COC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N)C)C=C1
CC(=O)[N:17](c1ccc(Cl)cc1F)[C@H:16]1[c:15]2[c:10]([cH:11][cH:12][cH:13][cH:14]2)[N:9]([C:7]([c:6]2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:22][cH:21]2)=[O:8])[C@@H:19]([CH3:20])[CH2:18]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[N:9]2[c:10]3[cH:11][cH:12][cH:13][cH:14][c:15]3[C@H:16]([NH2:17])[CH2:18][C@@H:19]2[CH3:...
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3F)C[C@@H]2C)cc1
COc1ccc(C(=O)N2c3ccccc3[C@H](N)C[C@@H]2C)cc1
null
null
null
Reduction
OtherReaction
d92dd7f766bc2fbe16dcf7a94e94f65a1bbe8d8b267946fd3311ac86741697b5
49e06ba3dca9c668787a59c7ab748b40e0239953b828b5dd26793ffc8ba0855c
O=C(c1ccccc1)N1CCCc2ccccc21
C-C(=O)-[N;H0;D3;+0:1](-[C:2](-[C:3])-[c:4])-c1:c:c:c(-Cl):c:c:1-F>>[C:3]-[C:2](-[NH2;D1;+0:1])-[c:4]
null
[]
null
null
null
null
N-(4-chloro-2-fluorophenyl)-N-[(2S,4R)-1-(4-methoxybenzoyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl]acetamide was made following general procedure G, substituting 4-methoxybenzoyl chloride for 4-fluorobenzoyl chloride. The amine-aryl coupling was performed differently to what is described in procedure G. Therefore (2S...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Tertiary amide
Primary amine
c1ccccc1
null
c1ccccc1.c1ccc2c(c1)CCC[NH]2
HF
null
null
null
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3F)C[C@@H]2C)cc1>>COc1ccc(C(=O)N2c3ccccc3[C@H](N)C[C@@H]2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-78633439ddf642a3a95eb0b43b1b09d7
CC(=O)Cl.COc1ccc(C(=O)N2c3ccccc3[C@H](Nc3ccc(Cl)cc3F)C[C@@H]2C)cc1>>COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3F)C[C@@H]2C)cc1
ClC1=CC(=C(C=C1)N[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C)F.C(C)(C)N(CC)C(C)C.C(C)(=O)Cl>>ClC1=CC(=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C)F
Cl[C:18]([CH3:19])=[O:20].[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[N:9]2[c:10]3[cH:11][cH:12][cH:13][cH:14][c:15]3[C@H:16]([NH:17][c:21]3[cH:22][cH:23][c:24]([Cl:25])[cH:26][c:27]3[F:28])[CH2:29][C@@H:30]2[CH3:31])[cH:32][cH:33]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[N:9]2[c:10]3[cH:11][cH:12][cH:...
CC(=O)Cl.COc1ccc(C(=O)N2c3ccccc3[C@H](Nc3ccc(Cl)cc3F)C[C@@H]2C)cc1
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3F)C[C@@H]2C)cc1
null
null
null
Acylation
N-alkylation of secondary amines with alkyl halides
b92e0bfd3d683c1f2a209adfe70a67ad7cb0d87749eb59e8fe0cf1689bc291e0
96cb0a2fed10552c5770a45a2d6523b47ac3e38928b4a9c698d8577451182dcd
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Cl-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[C:4]-[C:5](-[NH;D2;+0:6]-[c:7](:[c:8]):[c:9])-[c:10]>>[C:4]-[C:5](-[N;H0;D3;+0:6](-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3])-[c:7](:[c:8]):[c:9])-[c:10]
92
[{"value": 92.0, "product": "ClC1=CC(=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
To a solution of (2S,4R)-N-(4-chloro-2-fluorophenyl)-1-(4-methoxybenzoyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-amine (60 mg, 0.14 mmol, 1 equ.) in acetyl chloride (0.5 mL) was added diisopropylethylamine (25 uL, 0.14 mmol, 1 equ.). The mixture was stirred at room temperature for 16 h. The mixture was concentrated unde...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Secondary amine
Tertiary amide
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HCl
null
null
16
CC(=O)Cl.COc1ccc(C(=O)N2c3ccccc3[C@H](Nc3ccc(Cl)cc3F)C[C@@H]2C)cc1>>COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3F)C[C@@H]2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-185328c463a14c34a7f8240566847696
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(C#N)cc2)c2ccccc21.[OH-]>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(C(N)=O)cc2)c2ccccc21
Cl.ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)C#N)=O)C.[OH-].[K+].C(C)O>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C(=O)N)C=C1)C)C1=CC=C(C=C1)Cl
[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]([C:23]#[N:24])[cH:26][cH:27]2)[c:28]2[cH:29][cH:30][cH:31][cH:32][c:33]21.[OH-:25]>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(C#N)cc2)c2ccccc21.[OH-]
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(C(N)=O)cc2)c2ccccc21
null
null
O.C(Cl)Cl
Heteroatom Alkylation and Arylation
OtherReaction
1d1793919e847ed86dcb16487e62464531560dbf4782f9a5875bfe7e0477a3ec
d6f9d146e8ef95e62f1a3ab55a7e3b4ceec8856a5f71b6dccd4ad850f945b658
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
[N;H0;D1;+0:1]#[C;H0;D2;+0:2]-[c:3](:[c:4]):[c:5].[OH-;D0:6]>>[NH2;D1;+0:1]-[C;H0;D3;+0:2](=[O;H0;D1;+0:6])-[c:3](:[c:4]):[c:5]
null
[]
null
null
null
null
N-(4-chlorophenyl)-N-[(2S,4R)-1-(4-cyanobenzoyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl]acetamide (143 mg, 0.33 mmol) and potassium hydroxide (55 mg, 1.00 mmol)) were dissolved in water (150 mL), ethanol (3 mL) and heated to 70° C. for 4 h. The slurry was portioned between 1N HCl (until acidic) and methylene chloride...
10.6084/m9.figshare.5104873.v1
null
Nitrile
Primary amide
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
null
O.C(Cl)Cl
null
null
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(C#N)cc2)c2ccccc21.[OH-]>O.C(Cl)Cl>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(C(N)=O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-fe3797a7dbed47b6b5a5670b3a947a45
CCOC(=O)N1CCOc2ccc(C(=O)N3c4ccccc4C(N(C(C)=O)c4ccc(Cl)cc4)CC3C)cc21>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc3c(c2)NCCO3)c2ccccc21
C(C)OC(=O)N1CCOC2=C1C=C(C=C2)C(=O)N2C(CC(C1=CC=CC=C21)N(C2=CC=C(C=C2)Cl)C(C)=O)C>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C=1C=CC2=C(NCCO2)C1)C
CCOC(=O)[N:25]1[c:23]2[c:22]([cH:21][cH:20][c:19]([C:17]([N:16]3[CH:14]([CH3:15])[CH2:13][CH:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]4[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]4)[c:34]4[c:29]3[cH:30][cH:31][cH:32][cH:33]4)=[O:18])[cH:24]2)[O:28][CH2:27][CH2:26]1>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10...
CCOC(=O)N1CCOc2ccc(C(=O)N3c4ccccc4C(N(C(C)=O)c4ccc(Cl)cc4)CC3C)cc21
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc3c(c2)NCCO3)c2ccccc21
null
null
I[Si](C)(C)C.C(Cl)Cl
Reduction
Hydrogenolysis of tertiary amines
b9394cfd10271f5aae2de98b8422519c52d48ec7ce542c4d6938d462b9eccb91
20c36f41eeb07c3ba4437b51ba72e8ff3c22d0b27e7197b0e9af3127f331149f
O=C(c1ccc2c(c1)NCCO2)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-C-O-C(=O)-[N;H0;D3;+0:1]1-[C:2]-[C:3]-[#8:4]-[c:5]:[c:6]-1:[c:7]>>[c:7]:[c:6]1:[c:5]-[#8:4]-[C:3]-[C:2]-[NH;D2;+0:1]-1
null
[]
null
null
4
DAY
6-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid ethyl ester was dissolved in methylene chloride (3 mL) and iodotrimethylsilane (1 mL). After 4 days, the reaction was quenched with sat. aq. NaHCO3. The residue was partitioned between met...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether
Secondary amine
c1ccc2c(c1)[NH]CCO2
c1ccc2c(c1)NCCO2
c1ccccc1.c1ccc2c(c1)NCCO2.c1ccc2c(c1)CCC[NH]2
HO-
I[Si](C)(C)C.C(Cl)Cl
null
96
CCOC(=O)N1CCOc2ccc(C(=O)N3c4ccccc4C(N(C(C)=O)c4ccc(Cl)cc4)CC3C)cc21>I[Si](C)(C)C.C(Cl)Cl>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc3c(c2)NCCO3)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-516f5754b7e74eee9937bef93f434c35
ClCCl.O=C(Cl)C(=O)Cl.O=C(Cl)c1ccc(-n2ccc(C(F)(F)F)n2)cc1.O=C(Cl)c1ccc(F)cc1.O=C(O)c1ccc(-n2ccc(C(F)(F)F)n2)cc1.O=C(O)c1ccc(-n2ccc(C(F)(F)F)n2)cc1>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(-n3ccc(C(F)(F)F)n3)cc2)c2ccccc21
FC(C1=NN(C=C1)C1=CC=C(C(=O)Cl)C=C1)(F)F.FC(C1=NN(C=C1)C1=CC=C(C(=O)O)C=C1)(F)F.FC(C1=NN(C=C1)C1=CC=C(C(=O)O)C=C1)(F)F.C(C(=O)Cl)(=O)Cl.C(Cl)Cl.FC1=CC=C(C(=O)Cl)C=C1>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)N1N=C(C=C1)C(F)(F)F)=O)C
Cl[CH2:15][Cl:9].O=[C:1](Cl)[C:2](Cl)=[O:3].O=C(Cl)c1ccc(-n2ccc(C(F)(F)F)n2)[cH:38]c1.O=C(Cl)[c:5]1[cH:6][cH:7][c:8](F)[cH:10][cH:11]1.O=C(O)[c:35]1[cH:34][cH:39][c:12](-[n:4]2c[cH:13][c:14](C(F)(F)F)[n:16]2)[cH:37][cH:36]1.O[C:17](=[O:18])[c:19]1[cH:20][cH:21][c:22](-[n:23]2[cH:24][cH:25][c:26]([C:27]([F:28])([F:29])[...
ClCCl.O=C(Cl)C(=O)Cl.O=C(Cl)c1ccc(-n2ccc(C(F)(F)F)n2)cc1.O=C(Cl)c1ccc(F)cc1.O=C(O)c1ccc(-n2ccc(C(F)(F)F)n2)cc1.O=C(O)c1ccc(-n2ccc(C(F)(F)F)n2)cc1
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(-n3ccc(C(F)(F)F)n3)cc2)c2ccccc21
null
null
CN(C)C=O
Acylation
OtherReaction
7efd7aba43b99b4481b45a40f37b36546ded286afd60fc497e71c42fec6ea510
19511973ea5991daa9d61b03fb9ad8183e84f37a8d2ae444e2d675ead47ce978
O=C(c1ccc(-n2cccn2)cc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Cl-C(=O)-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[c;H0;D3;+0:4](-F):[c:5]:[c:6]:1.Cl-C(=O)-c1:c:[cH;D2;+0:7]:c(-n2:c:c:c(-C(-F)(-F)-F):n:2):c:c:1.Cl-[C;H0;D3;+0:8](=O)-[C;H0;D3;+0:9](-Cl)=[O;D1;H0:10].Cl-[CH2;D2;+0:11]-[Cl;H0;D1;+0:12].F-C(-F)(-F)-[c;H0;D3;+0:13]1:[cH;D2;+0:14]:c:[n;H0;D3;+0:15](-[c;H0;D3;+0:16]2:[cH;D2;+0:17]:[c:...
null
[]
null
null
null
null
N-(4-chlorophenyl)-N-((2S,4R)-2-methyl-1-{4-[3-(trifluoromethyl)-1H-pyrazol-1-yl]benzoyl}-1,2,3,4-tetrahydroquinolin-4-yl)acetamide was prepared following general procedure A, substituting 4-[3-(trifluoromethyl)-1H-pyrazol-1-yl]benzoyl chloride for 4-fluorobenzoyl chloride. (4-[3-(trifluoromethyl)-1H-pyrazol-1-yl]benzo...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Acyl halide.Acyl halide.Acyl halide.Trifluoro group.Trifluoro group.Aromatic halide.Primary halide.Primary halide.Carboxylic acid.Carboxylic acid
Aromatic halide.Tertiary amide.Tertiary amide
c1ccccc1.c1cn[nH]c1.c1ccccc1.c1ccccc1.c1cc[nH]n1
c1ccccc1.c1ccc2c(c1)CCC[NH]2
c1ccccc1.c1ccccc1.c1cc[nH]n1.c1ccc2c(c1)CCC[NH]2
HF
CN(C)C=O
null
null
ClCCl.O=C(Cl)C(=O)Cl.O=C(Cl)c1ccc(-n2ccc(C(F)(F)F)n2)cc1.O=C(Cl)c1ccc(F)cc1.O=C(O)c1ccc(-n2ccc(C(F)(F)F)n2)cc1.O=C(O)c1ccc(-n2ccc(C(F)(F)F)n2)cc1>CN(C)C=O>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(-n3ccc(C(F)(F)F)n3)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-534357b57cbd4470806b4d20a9c32b33
CCOC(C)=O.C[C@H]1C[C@@H](N)c2ccccc2N1C(=O)c1ccc2c(c1)OCCN2C.OB(O)c1ccc(Cl)cc1>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc3c(c2)OCCN3C)c2ccccc21
C(C)(=O)OCC.N[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC2=C(N(CCO2)C)C=C1)C.ClC1=CC=C(C=C1)B(O)O.C(C)N(CC)CC>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC2=C(N(CCO2)C)C=C1)C
CCO[C:2]([CH3:1])=[O:3].[NH2:4][C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]3[c:23]([cH:24]2)[O:25][CH2:26][CH2:27][N:28]3[CH3:29])[c:30]2[cH:31][cH:32][cH:33][cH:34][c:35]21.OB(O)[c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([C...
CCOC(C)=O.C[C@H]1C[C@@H](N)c2ccccc2N1C(=O)c1ccc2c(c1)OCCN2C.OB(O)c1ccc(Cl)cc1
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc3c(c2)OCCN3C)c2ccccc21
null
C(C)(=O)[O-].[Cu+2].C(C)(=O)[O-]
C(Cl)Cl
Acylation
OtherReaction
d5b79df0bcad37b68666465f98bdbf09561dfcc3b18a2acc5b3be323501cddff
d21a41b88b3a6857658a80208e904dc455b890b23aaf7d742d8a593a93afbd98
O=C(c1ccc2c(c1)OCCN2)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-C-O-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].O-B(-O)-[c;H0;D3;+0:4](:[c:5]:[c:6]):[c:7]:[c:8].[C:9]-[C:10](-[NH2;D1;+0:11])-[c:12]>>[C:9]-[C:10](-[N;H0;D3;+0:11](-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3])-[c;H0;D3;+0:4](:[c:5]:[c:6]):[c:7]:[c:8])-[c:12]
null
[]
60
CELSIUS
1
HOUR
To a solution of (2S,4R)-(4-amino-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-7-yl)-methanone (662 mg, 1.87 mmol) in methylene chloride (8 mL) was added 4-chlorophenylboronic acid (583 mg, 3.74 mmol), triethylamine (1.81 ml, 13.09 mmol) and copper(II)acetate (681 mg, 3.74 mmol). The...
10.6084/m9.figshare.5104873.v1
null
Ester.Primary amine.Boronic acid
Tertiary amide
c1ccccc1
c1ccccc1
c1ccccc1.c1ccc2c(c1)[NH]CCO2.c1ccc2c(c1)CCC[NH]2
HO-.B
C(C)(=O)[O-].[Cu+2].C(C)(=O)[O-].C(Cl)Cl
60
1
CCOC(C)=O.C[C@H]1C[C@@H](N)c2ccccc2N1C(=O)c1ccc2c(c1)OCCN2C.OB(O)c1ccc(Cl)cc1>C(C)(=O)[O-].[Cu+2].C(C)(=O)[O-].C(Cl)Cl>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc3c(c2)OCCN3C)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1a88f1be5bad4005a59d44751fa43e7f
CC(=O)Cl.C[C@H]1C[C@@H](Nc2ccc(Cl)cc2)c2ccccc2N1C(=O)c1ccc2c(c1)OCCN2C>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc3c(c2)OCCN3C)c2ccccc21
C(C)(=O)Cl.ClC1=CC=C(C=C1)N[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC2=C(N(CCO2)C)C=C1)C.C(C)(C)N(CC)C(C)C>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC2=C(N(CCO2)C)C=C1)C
Cl[C:2]([CH3:1])=[O:3].[NH:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]3[c:23]([cH:24]2)[O:25][CH2:26][CH2:27][N:28]3[CH3:29])[c:30]2[cH:31][cH:32][cH:33][cH:34][c:35]21>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[...
CC(=O)Cl.C[C@H]1C[C@@H](Nc2ccc(Cl)cc2)c2ccccc2N1C(=O)c1ccc2c(c1)OCCN2C
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc3c(c2)OCCN3C)c2ccccc21
null
null
C(Cl)Cl
Acylation
N-alkylation of secondary amines with alkyl halides
b92e0bfd3d683c1f2a209adfe70a67ad7cb0d87749eb59e8fe0cf1689bc291e0
96cb0a2fed10552c5770a45a2d6523b47ac3e38928b4a9c698d8577451182dcd
O=C(c1ccc2c(c1)OCCN2)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Cl-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[C:4]-[C:5](-[NH;D2;+0:6]-[c:7](:[c:8]):[c:9])-[c:10]>>[C:4]-[C:5](-[N;H0;D3;+0:6](-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3])-[c:7](:[c:8]):[c:9])-[c:10]
null
[]
null
null
4
HOUR
To a solution of (2S,4R)-[4-(4-Chloro-phenylamino)-2-methyl-3,4-dihydro-2H-quinolin-1-yl]-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-7-yl)-methanone (540 mg, 1.25 mmol) in methylene chloride (5 mL) was added diisopropylethylamine (0.240 mL, 1.37 mmol) followed by acetyl chloride (2 mL). The mixture was stirred at room t...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Secondary amine
Tertiary amide
null
null
c1ccccc1.c1ccc2c(c1)[NH]CCO2.c1ccc2c(c1)CCC[NH]2
HCl
C(Cl)Cl
null
4
CC(=O)Cl.C[C@H]1C[C@@H](Nc2ccc(Cl)cc2)c2ccccc2N1C(=O)c1ccc2c(c1)OCCN2C>C(Cl)Cl>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc3c(c2)OCCN3C)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-427b9a5f1e954eb8a5c3958395bcb62c
C=CCCC(=O)OCC.C[C@H]1C[C@@H](NC(=O)OCc2ccccc2)c2ccccc2N1C(=O)c1ccc(I)cc1>>CCOC(=O)CC/C=C/c1ccc(C(=O)N2c3ccccc3[C@H](NC(=O)OCc3ccccc3)C[C@@H]2C)cc1
IC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)NC(OCC2=CC=CC=C2)=O)C)C=C1.C(C)OC(CCC=C)=O.C(C)(=O)[O-].[K+].C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1>>C(C1=CC=CC=C1)OC(=O)N[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)/C=C/CCC(=O)OCC)C
[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][CH2:7][CH:8]=[CH2:9].I[c:10]1[cH:11][cH:12][c:13]([C:14](=[O:15])[N:16]2[c:17]3[cH:18][cH:19][cH:20][cH:21][c:22]3[C@H:23]([NH:24][C:25](=[O:26])[O:27][CH2:28][c:29]3[cH:30][cH:31][cH:32][cH:33][cH:34]3)[CH2:35][C@@H:36]2[CH3:37])[cH:38][cH:39]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[...
C=CCCC(=O)OCC.C[C@H]1C[C@@H](NC(=O)OCc2ccccc2)c2ccccc2N1C(=O)c1ccc(I)cc1
CCOC(=O)CC/C=C/c1ccc(C(=O)N2c3ccccc3[C@H](NC(=O)OCc3ccccc3)C[C@@H]2C)cc1
null
[Cl-].C(CCC)[N+](CCCC)(CCCC)CCCC.C(C)(=O)[O-].[Pd+2].C(C)(=O)[O-]
CN(C)C=O
C-C Coupling
OtherReaction
2d4a44695e29e4a9ab430c3b66736ad86dd99247e7216f16f3ca137abca78747
df8442c9f2045421fb18548edb9c6acaeb9710f63e741d9f72e0000ca35c948a
O=C(N[C@@H]1CCN(C(=O)c2ccccc2)c2ccccc21)OCc1ccccc1
I-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C:6]-[C:7]=[CH2;D1;+0:8]>>[C:6]/[C:7]=[CH;D2;+0:8]/[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]
83.3
[{"value": 83.0, "product": "C(C1=CC=CC=C1)OC(=O)N[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)/C=C/CCC(=O)OCC)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 83.3, "product": "C(C1=CC=CC=C1)OC(=O)N[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)/C=C/CCC(=O)OCC)C", "details": "CALCULATEDPERCENTYIELD",...
null
null
1
HOUR
To a solution of benzyl [(2S,4R)-1-(4-iodobenzoyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl]carbamate (0.6 g, 1.14 mmol) in DMF (15 mL) at room temperature was added pent-4-enoic acid ethyl ester (0.292 g, 2.28 mmol), potassium acetate (0.67 g, 6.84 mmol), palladium acetate (0.05 g, 0.228 mmol), tetrabutylammonium chlo...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Allyl
null
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HI
[Cl-].C(CCC)[N+](CCCC)(CCCC)CCCC.C(C)(=O)[O-].[Pd+2].C(C)(=O)[O-].CN(C)C=O
null
1
C=CCCC(=O)OCC.C[C@H]1C[C@@H](NC(=O)OCc2ccccc2)c2ccccc2N1C(=O)c1ccc(I)cc1>[Cl-].C(CCC)[N+](CCCC)(CCCC)CCCC.C(C)(=O)[O-].[Pd+2].C(C)(=O)[O-].CN(C)C=O>CCOC(=O)CC/C=C/c1ccc(C(=O)N2c3ccccc3[C@H](NC(=O)OCc3ccccc3)C[C@@H]2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3128afadddc3442999db123be835d0e1
CCOC(=O)CCCCc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1.[NH4+]>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(CCCCC(N)=O)cc2)c2ccccc21
CN(C)C(=[N+](C)C)ON1C2=C(C=CC=N2)N=N1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C=1C=CC2=C(C1)N=NN2O.[Cl-].[NH4+].C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)CCCCC(=O)OCC)C)C1=CC=C(C=C1)Cl.C([O-])([O-])=O.[K+].[K+]>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)CCCCC(=O)N)C)C1=CC=C(C=C1)Cl
CCO[C:27]([CH2:26][CH2:25][CH2:24][CH2:23][c:22]1[cH:21][cH:20][c:19]([C:17]([N:16]2[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]3[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]3)[c:37]3[c:32]2[cH:33][cH:34][cH:35][cH:36]3)=[O:18])[cH:31][cH:30]1)=[O:29].[NH4+:28]>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6]...
CCOC(=O)CCCCc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1.[NH4+]
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(CCCCC(N)=O)cc2)c2ccccc21
null
null
CN(C)C=O.CO
Acylation
OtherReaction
d5b10d4f469e7a196a3b04a6a9e159a7d90514b6df5b50c1197d4b1b774c04e1
adc0ef6f6c1340dd2dbab737c85bf17fc842769181c5db1a2b4f82b391b28f9f
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[C:4].[NH4+;D0:5]>>[C:4]-[C:3]-[C;H0;D3;+0:1](-[NH2;D1;+0:5])=[O;D1;H0:2]
null
[]
40
CELSIUS
18
HOUR
Ethyl 5-(4-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}phenyl)pentanoate (0.135 g, 0.25 mmol) was hydrolyzed to the acid by dissolving in 6 ml methanol and potassium carbonate (0.2 g in 4 ml water) was added. The mixture was heated to 40° C. for 24 hours and methanol was rem...
10.6084/m9.figshare.5104873.v1
null
Ester
Primary amide
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HO-
CN(C)C=O.CO
40
18
CCOC(=O)CCCCc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1.[NH4+]>CN(C)C=O.CO>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(CCCCC(N)=O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8009694dad56484686c2523b35f24ee9
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1>>COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccccc3)C[C@@H]2C)cc1
ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C>>COC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=CC=C2)C)C=C1
Cl[c:24]1[cH:23][cH:22][c:21]([N:17]([C@H:16]2[c:15]3[c:10]([cH:11][cH:12][cH:13][cH:14]3)[N:9]([C:7]([c:6]3[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:31][cH:30]3)=[O:8])[C@@H:28]([CH3:29])[CH2:27]2)[C:18]([CH3:19])=[O:20])[cH:26][cH:25]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[N:9]2[c:10]3[cH:11][cH:12][cH:13][cH:1...
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccccc3)C[C@@H]2C)cc1
null
[Pd]
CO
Functional Group Interconversion
Aromatic dehalogenation
b66818d3926a4463fb8e1c3d4a89e94e47b4d46960d4bdb7bcfbeeec427cfd4e
56de34d4a44cb25d9380269ee5e138b0f24b40a3a0db22c5508049dc775a861f
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Cl-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]>>[c:3]:[c:2]:[cH;D2;+0:1]:[c:4]:[c:5]
95.2
[{"value": 95.0, "product": "COC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=CC=C2)C)C=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 95.2, "product": "COC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=CC=C2)C)C=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
(2S,4R)-N-(4-Chloro-phenyl)-N-[1-(4-methoxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide (200 mg, 0.36 mmol) was dissolved in MeOH and a catalytic amount of Palladium on Carbon (10%) was added. The round bottom flask in which resided the resulting solution was evacuated and backfilled with hydrogen. Th...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
Other
[Pd].CO
null
8
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1>[Pd].CO>COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccccc3)C[C@@H]2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-00607726e7474170b55eb44769e4da10
COC(=O)C(C)(C)CCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1F>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)c(F)c2)c2ccccc21
COC(C(CCOC1=C(C=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C)F)(C)C)=O.[OH-].[Li+].Cl>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC(=C(OCCC(C(=O)O)(C)C)C=C1)F)C)C1=CC=C(C=C1)Cl
C[O:31][C:29]([C:26]([CH2:25][CH2:24][O:23][c:22]1[cH:21][cH:20][c:19]([C:17]([N:16]2[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]3[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]3)[c:40]3[c:35]2[cH:36][cH:37][cH:38][cH:39]3)=[O:18])[cH:34][c:32]1[F:33])([CH3:27])[CH3:28])=[O:30]>>[CH3:1][C:2](=[O:3])[N:...
COC(=O)C(C)(C)CCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1F
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)c(F)c2)c2ccccc21
null
null
CO.C1CCOC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
null
[]
null
null
1
HOUR
(2S,4R)-4-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-2-fluoro-phenoxy)-2,2-dimethyl-butyric acid methyl ester (100 mg) was dissolved in methanol/THF (1:1, 5 mL), and lithium hydroxide (1.0N, 1 mL) was added. After 1 hour, the reaction was acidified (HCl) and extracted from with...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
Other
CO.C1CCOC1
null
1
COC(=O)C(C)(C)CCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1F>CO.C1CCOC1>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)c(F)c2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-94f6cd23ee694e4c95608c31b58a9530
CC(=O)O.CC(C)n1ncc2cc(C(=O)N3c4ccccc4[C@H](N)C[C@@H]3C)ccc21.OB(O)c1ccc(Cl)cc1>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc3c(cnn3C(C)C)c2)c2ccccc21
Br.CC(=O)O.ClC1=CC=C(C=C1)B(O)O.C(C)N(CC)CC.N[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C=1C=C2C=NN(C2=CC1)C(C)C)C>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C=1C=C2C=NN(C2=CC1)C(C)C)C
O[C:2]([CH3:1])=[O:3].[NH2:4][C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]3[c:23]([cH:24][n:25][n:26]3[CH:27]([CH3:28])[CH3:29])[cH:30]2)[c:31]2[cH:32][cH:33][cH:34][cH:35][c:36]21.OB(O)[c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c...
CC(=O)O.CC(C)n1ncc2cc(C(=O)N3c4ccccc4[C@H](N)C[C@@H]3C)ccc21.OB(O)c1ccc(Cl)cc1
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc3c(cnn3C(C)C)c2)c2ccccc21
null
[Pd].C(C)(=O)[O-].[Cu+2].C(C)(=O)[O-]
ClCCl.N1=CC=CC=C1
Acylation
OtherReaction
b210d0749be0070914f49434c7ba750557c7c260e12a30bdff5816327ee8e242
49621307eb2c1cae0ffe16756553688e1e2d3ddd29578a63d6bc32ba3a602763
O=C(c1ccc2[nH]ncc2c1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
O-B(-O)-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].O-[C;H0;D3;+0:6](-[C;D1;H3:7])=[O;D1;H0:8].[C:9]-[C:10](-[NH2;D1;+0:11])-[c:12]>>[C:9]-[C:10](-[N;H0;D3;+0:11](-[C;H0;D3;+0:6](-[C;D1;H3:7])=[O;D1;H0:8])-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5])-[c:12]
null
[]
null
null
null
null
(2S,4R)-N-(4-Chloro-phenyl)-N-[1-(1-isopropyl-1H-indazole-5-carbonyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide was prepared following general procedure G, substituting 1-Isopropyl-1H-indazole-5-carbonyl chloride for 4-fluorobenzoyl chloride. (1-Isopropyl-1H-indazole-5-carbonyl chloride was prepared in three...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine.Boronic acid
Tertiary amide
c1ccccc1
c1ccccc1
c1ccccc1.c1ccc2n[nH]cc2c1.c1ccc2c(c1)CCC[NH]2
HO-.B
[Pd].C(C)(=O)[O-].[Cu+2].C(C)(=O)[O-].ClCCl.N1=CC=CC=C1
null
null
CC(=O)O.CC(C)n1ncc2cc(C(=O)N3c4ccccc4[C@H](N)C[C@@H]3C)ccc21.OB(O)c1ccc(Cl)cc1>[Pd].C(C)(=O)[O-].[Cu+2].C(C)(=O)[O-].ClCCl.N1=CC=CC=C1>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc3c(cnn3C(C)C)c2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a92fb496713c4fc5871cfb210e11746e
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cnn(C(C)C)c2)c2ccccc21.CC(C)n1cc(C(=O)Cl)cn1.Cc1nn(C)c2sc(C(=O)O)cc12>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc3c(C)nn(C)c3s2)c2ccccc21.Cc1nn(C)c2sc(C(=O)Cl)cc12
CN1N=C(C2=C1SC(=C2)C(=O)O)C.C(C(=O)Cl)(=O)Cl.ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C=1C=NN(C1)C(C)C)C.C(C)(C)N1N=CC(=C1)C(=O)Cl>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC2=C(N(N=C2C)C)S1)C.CN1N=C(C2=C1SC(=C2)C(=O)Cl)C
CC(C)n1nc[c:19]([C:17]([N:16]2[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]3[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]3)[c:34]3[c:29]2[cH:30][cH:31][cH:32][cH:33]3)=[O:18])[cH:20]1.C[CH:26]([CH3:23])[n:25]1[n:24][cH:22][c:21](C(=O)[Cl:45])[cH:27]1.O[C:43]([c:42]1[s:28][c:40]2[n:38]([CH3:39])[n:37][...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cnn(C(C)C)c2)c2ccccc21.CC(C)n1cc(C(=O)Cl)cn1.Cc1nn(C)c2sc(C(=O)O)cc12
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc3c(C)nn(C)c3s2)c2ccccc21.Cc1nn(C)c2sc(C(=O)Cl)cc12
null
null
ClCCl.CN(C)C=O
C-C Coupling
OtherReaction
15c91b93e844b7d740f458a2fea8a78b27c46351434cff9c909523c1228b4cfc
edd0926fab5e8066ac1a42785cd03484ec38f412dfee015a3bcc3bcaf826acdc
O=C(c1cc2cn[nH]c2s1)N1CC[C@@H](Nc2ccccc2)c2ccccc21.c1cc2cn[nH]c2s1
C-C(-C)-n1:[cH;D2;+0:1]:[c;H0;D3;+0:2](-[C:3](=[O;D1;H0:4])-[#7:5](-[C:6])-[c:7]):c:n:1.C-[CH;D3;+0:8](-[CH3;D1;+0:9])-[#7;a:10]1:[#7;a:11]:[cH;D2;+0:12]:[c;H0;D3;+0:13](-C(=O)-[Cl;H0;D1;+0:14]):[cH;D2;+0:15]:1.O-[C;H0;D3;+0:16](=[O;D1;H0:17])-[c;H0;D3;+0:18]1:[c:19]:[c:20]2:[c:21](-[C;D1;H3:22]):[#7;a:23]:[#7;a:24](-[...
null
[]
null
null
null
null
N-(4-Chlorophenyl)-N-{(2S,4R)-1-[(1,3-dimethyl-1H-thieno[2,3-c]pyrazol-5-yl)carbonyl]-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl}acetamide was prepared following the procedure for N-(4-chlorophenyl)-N-{(2S,4R)-1-[(1-isopropyl-1H-pyrazol-4-yl)carbonyl]-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl}acetamide substituting 1,3-di...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Carboxylic acid
Acyl halide
c1cn[nH]c1.c1cn[nH]c1.c1cc2cn[nH]c2s1
c1cc2c[nH]nc2s1.c1cc2c[nH]nc2s1
c1ccccc1.c1cc2c[nH]nc2s1.c1ccc2c(c1)CCC[NH]2.c1cc2c[nH]nc2s1
HO-
ClCCl.CN(C)C=O
null
null
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cnn(C(C)C)c2)c2ccccc21.CC(C)n1cc(C(=O)Cl)cn1.Cc1nn(C)c2sc(C(=O)O)cc12>ClCCl.CN(C)C=O>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc3c(C)nn(C)c3s2)c2ccccc21.Cc1nn(C)c2sc(C(=O)Cl)cc12
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b278750930c742c0af53f041ab8367ae
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3cccc4c3ccn4C(=O)OC(C)(C)C)C[C@@H]2C)cc1>>COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3cccc4[nH]ccc34)C[C@@H]2C)cc1
C(C)(=O)N(C1=C2C=CN(C2=CC=C1)C(=O)OC(C)(C)C)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C>>N1C=CC2=C(C=CC=C12)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C
CC(C)(C)OC(=O)[n:26]1[c:25]2[cH:24][cH:23][cH:22][c:21]([N:17]([C@H:16]3[c:15]4[c:10]([cH:11][cH:12][cH:13][cH:14]4)[N:9]([C:7]([c:6]4[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:34][cH:33]4)=[O:8])[C@@H:31]([CH3:32])[CH2:30]3)[C:18]([CH3:19])=[O:20])[c:29]2[cH:28][cH:27]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[N:9]2...
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3cccc4c3ccn4C(=O)OC(C)(C)C)C[C@@H]2C)cc1
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3cccc4[nH]ccc34)C[C@@H]2C)cc1
null
null
Cl.O1CCOCC1
Reduction
Boc amine deprotection
42add5cbb5098100ca964321579ee6eb449e9641492081de05db5169b8facbfb
e1bf5a54b1f87284564f107662531aec2aff7de801e4606340967b38924afb28
O=C(c1ccccc1)N1CC[C@@H](Nc2cccc3[nH]ccc23)c2ccccc21
C-C(-C)(-C)-O-C(=O)-[n;H0;D3;+0:1]1:[c:2]:[c:3]:[c:4]:[c:5]:1:[c:6]>>[c:6]:[c:5]1:[c:4]:[c:3]:[c:2]:[nH;D2;+0:1]:1
28
[{"value": 28.0, "product": "N1C=CC2=C(C=CC=C12)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 25.9, "product": "N1C=CC2=C(C=CC=C12)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C", "details": "CALCULATEDPERCENTYIELD", "is_desired...
null
null
null
null
tert-Butyl 4-{acetyl[(2S,4R)-1-(4-methoxybenzoyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl]amino}-1H-indole-1-carboxylate (0.035 g, 0.068 mmol) was stirred in 4 N HCl in dioxane (1 mL) for 24 h and then evaporated to dryness. The residue was dissolved in ethyl acetate, washed with 1N NaOH, water, brine, dried over sodi...
10.6084/m9.figshare.5104873.v1
null
Ether.Boc
null
c1cccc2[nH]ccc12
c1ccc2[nH]ccc2c1
c1ccccc1.c1ccc2[nH]ccc2c1.c1ccc2c(c1)CCC[NH]2
HO-
Cl.O1CCOCC1
null
null
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3cccc4c3ccn4C(=O)OC(C)(C)C)C[C@@H]2C)cc1>Cl.O1CCOCC1>COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3cccc4[nH]ccc34)C[C@@H]2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9539a104c8c94838b2af679d2bb9327b
COC(=O)C(C)(C)CCN(C)c1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N(C)CCC(C)(C)C(=O)O)cc2)c2ccccc21
C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)N(CCC(C(=O)OC)(C)C)C)C)C1=CC=C(C=C1)Cl.[OH-].[Na+]>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)N(CCC(C(=O)O)(C)C)C)C)C1=CC=C(C=C1)Cl
C[O:32][C:30]([C:27]([CH2:26][CH2:25][N:23]([c:22]1[cH:21][cH:20][c:19]([C:17]([N:16]2[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]3[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]3)[c:40]3[c:35]2[cH:36][cH:37][cH:38][cH:39]3)=[O:18])[cH:34][cH:33]1)[CH3:24])([CH3:28])[CH3:29])=[O:31]>>[CH3:1][C:2](=[O:3...
COC(=O)C(C)(C)CCN(C)c1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N(C)CCC(C)(C)C(=O)O)cc2)c2ccccc21
null
null
CO.O1CCCC1.O
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
null
[]
40
CELSIUS
null
null
Methyl 4-[(4-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}phenyl)(methyl)amino]-2,2-dimethylbutanoate was dissolved in methanol/tetrahydrofuran/water (2/1/1) then sodium hydroxide (3 equivalents) was added and reaction mixture heated to 40° C. for 2 h. The mixture was concent...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
Other
CO.O1CCCC1.O
40
null
COC(=O)C(C)(C)CCN(C)c1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1>CO.O1CCCC1.O>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N(C)CCC(C)(C)C(=O)O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-77f9ed3a9e87443c81d3f56ab132efd9
CC(=O)Cl.COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)CO)c3ccc(Cl)cc3)C[C@@H]2C)cc1>>COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)COC(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
ClC1=CC=C(C=C1)N(C(CO)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C.FC1=CC=C(C(=O)Cl)C=C1.C(C)(=O)Cl>>C(C)(=O)OCC(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C)C1=CC=C(C=C1)Cl
Cl[C:22]([CH3:23])=[O:24].[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[N:9]2[c:10]3[cH:11][cH:12][cH:13][cH:14][c:15]3[C@H:16]([N:17]([C:18](=[O:19])[CH2:20][OH:21])[c:25]3[cH:26][cH:27][c:28]([Cl:29])[cH:30][cH:31]3)[CH2:32][C@@H:33]2[CH3:34])[cH:35][cH:36]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[N:9]...
CC(=O)Cl.COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)CO)c3ccc(Cl)cc3)C[C@@H]2C)cc1
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)COC(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
null
null
null
Acylation
Schotten-Baumann to ester
6cefe709828c5bd4655f254e75d5dff9e8876e192e7dd47256c1bc0067bc5291
d8a7643b81ed07a6f633aa99465180dfa0565e61ae25aef36338ebb9837c9cef
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Cl-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[C:4]-[#7:5](-[c:6])-[C:7](=[O;D1;H0:8])-[C:9]-[OH;D1;+0:10]>>[C:4]-[#7:5](-[c:6])-[C:7](=[O;D1;H0:8])-[C:9]-[O;H0;D2;+0:10]-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3]
null
[]
null
null
null
null
N-(4-chlorophenyl)-2-hydroxy-N-[(2S,4R)-1-(4-methoxybenzoyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl]acetamide was made following general procedure G, substituting 4-methoxybenzoyl chloride for 4-fluorobenzoyl chloride. Procedure A was followed further substituting acetoxyacetylchloride for acetyl chloride in the last...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary alcohol
Ester
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HCl
null
null
null
CC(=O)Cl.COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)CO)c3ccc(Cl)cc3)C[C@@H]2C)cc1>>COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)COC(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b4fb5c09234746ec83b42e3c0c9e2e37
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)COC(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1>>COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)CO)c3ccc(Cl)cc3)C[C@@H]2C)cc1
C(C)(=O)OCC(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C)C1=CC=C(C=C1)Cl.C([O-])([O-])=O.[K+].[K+]>>ClC1=CC=C(C=C1)N(C(CO)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C
CC(=O)[O:21][CH2:20][C:18]([N:17]([C@H:16]1[c:15]2[c:10]([cH:11][cH:12][cH:13][cH:14]2)[N:9]([C:7]([c:6]2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:33][cH:32]2)=[O:8])[C@@H:30]([CH3:31])[CH2:29]1)[c:22]1[cH:23][cH:24][c:25]([Cl:26])[cH:27][cH:28]1)=[O:19]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[N:9]2[c:10]3[cH:11][c...
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)COC(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)CO)c3ccc(Cl)cc3)C[C@@H]2C)cc1
null
null
O.CO
Reduction
Hydrolysis or Hydrogenolysis of Carboxylic Esters or Thioesters
21d61543c6ec8a8cebe1b3ef55ef3dd20acbf79a4f1c12a7fb51e32be7a3248a
1fbcd628a0426673c5d10aa49a977cd2d1ae02a8cdf57bbb10d94aa03a94e937
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-C(=O)-[O;H0;D2;+0:1]-[C:2]-[C:3](=[O;D1;H0:4])-[#7:5](-[C:6])-[c:7]>>[C:6]-[#7:5](-[c:7])-[C:3](=[O;D1;H0:4])-[C:2]-[OH;D1;+0:1]
84
[{"value": 84.0, "product": "ClC1=CC=C(C=C1)N(C(CO)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 83.4, "product": "ClC1=CC=C(C=C1)N(C(CO)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": fal...
null
null
4
HOUR
2-{(4-Chlorophenyl)[(2S,4R)-1-(4-methoxybenzoyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl]amino}-2-oxoethyl acetate (496 mg, 0.98 mmol, 1 eq.) was dissolved in methanol (12 ml). A solution of potassium carbonate (1.08 g, 7.84 mmol, 8 eq.) in water (5 ml) was added and reaction mixture was stirred at room temperature fo...
10.6084/m9.figshare.5104873.v1
null
Ester
Primary alcohol
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HO-
O.CO
null
4
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)COC(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1>O.CO>COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)CO)c3ccc(Cl)cc3)C[C@@H]2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-47125615988f44448d32b8b079878f43
CCOC(=O)N1CCOc2ccc(C(=O)N3c4ccccc4[C@H](N)C[C@@H]3C)cc21.CCOC(C)=O.OB(O)c1ccc(Cl)cc1>>CCOC(=O)N1CCOc2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc21
C(C)(=O)OCC.C(C)OC(=O)N1CCOC2=C1C=C(C=C2)C(=O)N2[C@H](C[C@H](C1=CC=CC=C21)N)C.ClC1=CC=C(C=C1)B(O)O.C(C)N(CC)CC>>C(C)OC(=O)N1CCOC2=C1C=C(C=C2)C(=O)N2[C@H](C[C@H](C1=CC=CC=C21)N(C2=CC=C(C=C2)Cl)C(C)=O)C
[CH3:1][CH2:2][O:3][C:4](=[O:5])[N:6]1[CH2:7][CH2:8][O:9][c:10]2[cH:11][cH:12][c:13]([C:14](=[O:15])[N:16]3[c:17]4[cH:18][cH:19][cH:20][cH:21][c:22]4[C@H:23]([NH2:24])[CH2:35][C@@H:36]3[CH3:37])[cH:38][c:39]21.CCO[C:25]([CH3:26])=[O:27].OB(O)[c:28]1[cH:29][cH:30][c:31]([Cl:32])[cH:33][cH:34]1>>[CH3:1][CH2:2][O:3][C:4](...
CCOC(=O)N1CCOc2ccc(C(=O)N3c4ccccc4[C@H](N)C[C@@H]3C)cc21.CCOC(C)=O.OB(O)c1ccc(Cl)cc1
CCOC(=O)N1CCOc2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc21
null
C(C)(=O)[O-].[Cu+2].C(C)(=O)[O-]
C(Cl)Cl
Acylation
OtherReaction
d5b79df0bcad37b68666465f98bdbf09561dfcc3b18a2acc5b3be323501cddff
d21a41b88b3a6857658a80208e904dc455b890b23aaf7d742d8a593a93afbd98
O=C(c1ccc2c(c1)NCCO2)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-C-O-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].O-B(-O)-[c;H0;D3;+0:4](:[c:5]:[c:6]):[c:7]:[c:8].[C:9]-[C:10](-[NH2;D1;+0:11])-[c:12]>>[C:9]-[C:10](-[N;H0;D3;+0:11](-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3])-[c;H0;D3;+0:4](:[c:5]:[c:6]):[c:7]:[c:8])-[c:12]
null
[]
60
CELSIUS
1
HOUR
To a solution of (2S,4R)-6-(4-Amino-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl)-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid ethyl ester (470 mg, 1.18 mmol) in methylene chloride was added 4-chlorophenylboronic acid (368 mg, 2.36 mmol), triethylamine (1.31 mL, 9.42 mmol) and copper(II)acetate (429 mg, 2.36 mmol). ...
10.6084/m9.figshare.5104873.v1
null
Ester.Primary amine.Boronic acid
Tertiary amide
c1ccccc1
c1ccccc1
c1ccc2c(c1)[NH]CCO2.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HO-.B
C(C)(=O)[O-].[Cu+2].C(C)(=O)[O-].C(Cl)Cl
60
1
CCOC(=O)N1CCOc2ccc(C(=O)N3c4ccccc4[C@H](N)C[C@@H]3C)cc21.CCOC(C)=O.OB(O)c1ccc(Cl)cc1>C(C)(=O)[O-].[Cu+2].C(C)(=O)[O-].C(Cl)Cl>CCOC(=O)N1CCOc2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2b7043dea18c49ecaa89891f8f1cfd79
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cnn(C(C)C)c2)c2ccccc21.CC(C)n1cc(C(=O)Cl)cn1.CCOC(=O)CBr.CN(C)C=O.O=C([O-])[O-]>>CCOC(=O)COc1cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)on1.CCOC(=O)COc1cc(C(=O)OC)on1
CN(C)C=O.ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C=1C=NN(C1)C(C)C)C.C(C)(C)N1N=CC(=C1)C(=O)Cl.BrCC(=O)OCC.[I-].[K+].C([O-])([O-])=O.[K+].[K+]>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC(=NO1)OCC(=O)OCC)C)C1=CC=C(C=C1)Cl.C(C)OC(COC1=NOC(=C1)C(=O)OC)=O
C[CH:8](C)[n:36]1[cH:9][c:10]([C:11](=[O:12])[N:13]2[c:14]3[cH:15][cH:16][cH:17][cH:18][c:19]3[C@H:20]([N:21]([C:22]([CH3:23])=[O:24])[c:25]3[cH:26][cH:27][c:28]([Cl:29])[cH:30][cH:31]3)[CH2:32][C@@H:33]2[CH3:34])[cH:44][n:52]1.C[CH:2](n1nc[c:46]([C:47](Cl)=[O:48])[cH:45]1)[CH3:1].Br[CH2:42][C:40]([O:39][CH2:38][CH3:37...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cnn(C(C)C)c2)c2ccccc21.CC(C)n1cc(C(=O)Cl)cn1.CCOC(=O)CBr.CN(C)C=O.O=C([O-])[O-]
CCOC(=O)COc1cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)on1.CCOC(=O)COc1cc(C(=O)OC)on1
null
null
O
C-C Coupling
OtherReaction
08810427c4c0e31dafc8f7ebd66e20edb12d5450aa08e906222990d5b22b78ec
daf6492869802736994e63bf3927f2ca6eb2dd2bc3c50c4a1f461dbd67fd8762
O=C(c1ccno1)N1CC[C@@H](Nc2ccccc2)c2ccccc21.c1cnoc1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C:5].C-N(-[CH3;D1;+0:6])-[CH;D2;+0:7]=[O;H0;D1;+0:8].C-[CH;D3;+0:9](-C)-[n;H0;D3;+0:10]1:[cH;D2;+0:11]:[c;H0;D3;+0:12](-[C:13](=[O;D1;H0:14])-[#7:15](-[C:16])-[c:17]):[cH;D2;+0:18]:[n;H0;D2;+0:19]:1.C-[CH;D3;+0:20](-[C;D1;H3:21])-n1:[cH;D2;+0:22]:[c;H0;D3;+0:23](-[C;H0;D3;+0...
60
[{"value": 60.0, "product": "C(C)OC(COC1=NOC(=C1)C(=O)OC)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Ethyl [(5-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}isoxazol-3-yl)oxy]acetate was prepared following the procedure for N-(4-chlorophenyl)-N-{(2S,4R)-1-[(1-isopropyl-1H-pyrazol-4-yl)carbonyl]-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl}acetamide substituting ethyl {[5-(chloroc...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary halide.Ester.Tertiary amide
Ester.Ester.Ester.Ether.Ether
c1cn[nH]c1.c1cn[nH]c1
c1cnoc1.c1cnoc1
c1cnoc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2.c1cnoc1
HCl.Br-
O
null
null
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cnn(C(C)C)c2)c2ccccc21.CC(C)n1cc(C(=O)Cl)cn1.CCOC(=O)CBr.CN(C)C=O.O=C([O-])[O-]>O>CCOC(=O)COc1cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)on1.CCOC(=O)COc1cc(C(=O)OC)on1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ef2e8696b1f84443b63d5a49f32f0a8e
CCOC(=O)COc1cc(C(=O)OC)on1>>O=C(O)COc1cc(C(=O)O)on1
C(C)OC(COC1=NOC(=C1)C(=O)OC)=O.[OH-].[Na+]>>C(=O)(O)COC1=NOC(=C1)C(=O)O
CC[O:3][C:2](=[O:1])[CH2:4][O:5][c:6]1[cH:7][c:8]([C:9](=[O:10])[O:11]C)[o:12][n:13]1>>[O:1]=[C:2]([OH:3])[CH2:4][O:5][c:6]1[cH:7][c:8]([C:9](=[O:10])[OH:11])[o:12][n:13]1
CCOC(=O)COc1cc(C(=O)OC)on1
O=C(O)COc1cc(C(=O)O)on1
null
null
CO
Deprotection
OtherReaction
6e62db7aac546f574bcfb83067ba8906c30fcbfedfc37aa16b5eaad33833f45a
ed5fed81ba501ef41c88831ec6b9463b899bfdd0815c4145ae51c79addb226d0
c1cnoc1
C-C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4].C-[O;H0;D2;+0:5]-[C:6](=[O;D1;H0:7])-[c:8]:[#8;a:9]:[#7;a:10]>>[#7;a:10]:[#8;a:9]:[c:8]-[C:6](=[O;D1;H0:7])-[OH;D1;+0:5].[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
86
[{"value": 86.0, "product": "C(=O)(O)COC1=NOC(=C1)C(=O)O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Ethyl [(5-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}isoxazol-3-yl)oxy]acetate was prepared following the procedure for N-(4-chlorophenyl)-N-{(2S,4R)-1-[(1-isopropyl-1H-pyrazol-4-yl)carbonyl]-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl}acetamide substituting ethyl {[5-(chloroc...
10.6084/m9.figshare.5104873.v1
null
Ester.Ester
Carboxylic acid.Carboxylic acid
null
null
c1cnoc1
Other
CO
null
null
CCOC(=O)COc1cc(C(=O)OC)on1>CO>O=C(O)COc1cc(C(=O)O)on1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d33ca123addf4bd2bf9b5f3beef49be2
CCOC(=O)COc1cc(C(=O)O)on1.O=C(Cl)C(=O)Cl>>CCOC(=O)COc1cc(C(=O)Cl)on1
C(C)OC(COC1=NOC(=C1)C(=O)O)=O.C(C(=O)Cl)(=O)Cl.CN(C)C=O>>ClC(=O)C1=CC(=NO1)OCC(=O)OCC
O[C:11]([c:10]1[cH:9][c:8]([O:7][CH2:6][C:4]([O:3][CH2:2][CH3:1])=[O:5])[n:15][o:14]1)=[O:12].O=C(Cl)C(=O)[Cl:13]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][O:7][c:8]1[cH:9][c:10]([C:11](=[O:12])[Cl:13])[o:14][n:15]1
CCOC(=O)COc1cc(C(=O)O)on1.O=C(Cl)C(=O)Cl
CCOC(=O)COc1cc(C(=O)Cl)on1
null
null
ClCCl
Functional Group Interconversion
Alcohol to chloride_Other
013cec2edeb273a7a148f349d36a52d99ff4e7bcf8eed78085df830088e387ac
aedb1f68dc5b7eb0583043e1125b741382b17974140a2f46554f0110e2ddc884
c1cnoc1
Cl-C(=O)-C(=O)-[Cl;H0;D1;+0:1].O-[C;H0;D3;+0:2](=[O;D1;H0:3])-[c:4]1:[#8;a:5]:[#7;a:6]:[c:7]:[c:8]:1>>[Cl;H0;D1;+0:1]-[C;H0;D3;+0:2](=[O;D1;H0:3])-[c:4]1:[#8;a:5]:[#7;a:6]:[c:7]:[c:8]:1
null
[]
null
null
null
null
Ethyl [(5-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}isoxazol-3-yl)oxy]acetate was prepared following the procedure for N-(4-chlorophenyl)-N-{(2S,4R)-1-[(1-isopropyl-1H-pyrazol-4-yl)carbonyl]-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl}acetamide substituting ethyl {[5-(chloroc...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Acyl halide.Carboxylic acid
Acyl halide
null
null
c1cnoc1
HCl
ClCCl
null
null
CCOC(=O)COc1cc(C(=O)O)on1.O=C(Cl)C(=O)Cl>ClCCl>CCOC(=O)COc1cc(C(=O)Cl)on1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-20e6ab1c70c14c8a9169fd6d3e4de842
CCOC(=O)COc1cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)on1>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc(OCC(=O)O)no2)c2ccccc21
C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC(=NO1)OCC(=O)OCC)C)C1=CC=C(C=C1)Cl.O.[OH-].[Li+]>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC(=NO1)OCC(=O)O)C)C1=CC=C(C=C1)Cl
CC[O:26][C:24]([CH2:23][O:22][c:21]1[cH:20][c:19]([C:17]([N:16]2[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]3[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]3)[c:34]3[c:29]2[cH:30][cH:31][cH:32][cH:33]3)=[O:18])[o:28][n:27]1)=[O:25]>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11...
CCOC(=O)COc1cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)on1
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc(OCC(=O)O)no2)c2ccccc21
null
null
CO
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(c1ccno1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
60
[{"value": 60.0, "product": "C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC(=NO1)OCC(=O)O)C)C1=CC=C(C=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Ethyl [(5-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}isoxazol-3-yl)oxy]acetate was prepared following the procedure for N-(4-chlorophenyl)-N-{(2S,4R)-1-[(1-isopropyl-1H-pyrazol-4-yl)carbonyl]-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl}acetamide substituting ethyl {[5-(chloroc...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.c1cnoc1.c1ccc2c(c1)CCC[NH]2
Other
CO
null
null
CCOC(=O)COc1cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)on1>CO>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc(OCC(=O)O)no2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a9da0719d6ca484cbe4fa7c148a5d084
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cnn(C(C)C)c2)c2ccccc21.CC(C)n1cc(C(=O)Cl)cn1.CCOC(=O)C(C)(C)CCBr.CN(C)C=O.O=C([O-])[O-]>>CCOC(=O)C(C)(C)CCOc1cc(C(=O)Cl)on1.CCOC(=O)C(C)(C)CCOc1cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)on1.CCOC(=O)C(C)(C)CCOc1cc(C(=O)OC)on1
CN(C)C=O.ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C=1C=NN(C1)C(C)C)C.C(C)(C)N1N=CC(=C1)C(=O)Cl.BrCCC(C(=O)OCC)(C)C.[I-].[K+].C([O-])([O-])=O.[K+].[K+]>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC(=NO1)OCCC(C(=O)OCC)(C)C)C)C1=CC=C(C=C1)Cl.ClC(=O)C1=CC(=NO1)OCCC(C(=O)OCC)(C)C.C(C)OC(C(CCOC1=NOC(=...
[CH3:12][CH:21]([n:19]1[cH:32][c:33]([C:34](=[O:35])[N:36]2[c:37]3[cH:38][cH:39][cH:40][cH:41][c:42]3[C@H:43]([N:44]([C:45]([CH3:46])=[O:47])[c:48]3[cH:49][cH:50][c:51]([Cl:52])[cH:53][cH:54]3)[CH2:55][C@@H:56]2[CH3:57])[cH:71][n:79]1)[CH3:28].n1([CH:61]([CH3:60])[CH3:68])[cH:13][c:14]([C:15](=[O:16])[Cl:17])[cH:74][n:...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cnn(C(C)C)c2)c2ccccc21.CC(C)n1cc(C(=O)Cl)cn1.CCOC(=O)C(C)(C)CCBr.CN(C)C=O.O=C([O-])[O-]
CCOC(=O)C(C)(C)CCOc1cc(C(=O)Cl)on1.CCOC(=O)C(C)(C)CCOc1cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)on1.CCOC(=O)C(C)(C)CCOc1cc(C(=O)OC)on1
null
null
O
Aromatic Heterocycle Formation
OtherReaction
3a2cd6134da7826e7429281d49e797b26a247553ce02cb083c2ac3164bccfd3b
d9387545c091c51eabac81afe0f00c5d3f07ac9c7c9540c1c44a5bab97382420
O=C(c1ccno1)N1CC[C@@H](Nc2ccccc2)c2ccccc21.c1cnoc1.c1cnoc1
Br-[CH2;D2;+0:1]-[C:2]-[C:3]-[C:4](-[#8:5])=[O;D1;H0:6].[C;D1;H3:7]-[CH;D3;+0:8](-[CH3;D1;+0:9])-n1:[cH;D2;+0:10]:[c;H0;D3;+0:11](-[C:12](-[Cl;D1;H0:13])=[O;D1;H0:14]):[cH;D2;+0:15]:[n;H0;D2;+0:16]:1.[CH3;D1;+0:17]-N(-[CH3;D1;+0:18])-[CH;D2;+0:19]=[O;H0;D1;+0:20].[C:21]-[#7:22](-[C:23](=[O;D1;H0:24])-[c;H0;D3;+0:25]1:[...
null
[]
null
null
null
null
Ethyl 4-[(5-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}isoxazol-3-yl)oxy]-2,2-dimethylbutanoate was prepared following the procedure for N-(4-chlorophenyl)-N-{(2S,4R)-1-[(1-isopropyl-1H-pyrazol-4-yl)carbonyl]-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl}acetamide, substituting ...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Tertiary amide
Ester.Ester.Ester.Ether.Ether.Ether
c1cn[nH]c1.c1cn[nH]c1
c1cnoc1.c1cnoc1.c1cnoc1
c1cnoc1.c1cnoc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2.c1cnoc1
Br-
O
null
null
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cnn(C(C)C)c2)c2ccccc21.CC(C)n1cc(C(=O)Cl)cn1.CCOC(=O)C(C)(C)CCBr.CN(C)C=O.O=C([O-])[O-]>O>CCOC(=O)C(C)(C)CCOc1cc(C(=O)Cl)on1.CCOC(=O)C(C)(C)CCOc1cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)on1.CCOC(=O)C(C)(C)CCOc1cc(C(=O)OC)on1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5804354907264415ad42fcd73a5917ca
COc1ccc(C(=O)N2c3ccccc3[C@H](NC(=O)OCc3ccccc3)C[C@@H]2C)cc1>>COc1ccc(C(=O)N2c3ccccc3[C@H](N)C[C@@H]2C)cc1
C(C1=CC=CC=C1)OC(N[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C)=O>>N[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)OC)C
O=C(OCc1ccccc1)[NH:17][C@H:16]1[c:15]2[c:10]([cH:11][cH:12][cH:13][cH:14]2)[N:9]([C:7]([c:6]2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:22][cH:21]2)=[O:8])[C@@H:19]([CH3:20])[CH2:18]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[N:9]2[c:10]3[cH:11][cH:12][cH:13][cH:14][c:15]3[C@H:16]([NH2:17])[CH2:18][C@@H:19]2[CH3:20])[...
COc1ccc(C(=O)N2c3ccccc3[C@H](NC(=O)OCc3ccccc3)C[C@@H]2C)cc1
COc1ccc(C(=O)N2c3ccccc3[C@H](N)C[C@@H]2C)cc1
null
[Pd]
C(C)O
Reduction
Hydrogenolysis of amides/imides/carbamates
087b6600ba91d3df931fe6979f2445c192cbfd59e04fd2d8a10f7c7573ac669f
4e549866ec1acadec4c84aaf8495992a28ec78d8ea5ef1b9f44dd843b0dcb7d4
O=C(c1ccccc1)N1CCCc2ccccc21
O=C(-O-C-c1:c:c:c:c:c:1)-[NH;D2;+0:1]-[C:2](-[C:3])-[c:4]>>[C:3]-[C:2](-[NH2;D1;+0:1])-[c:4]
null
[]
null
null
4
HOUR
(2S,4R)-[1-(4-methoxybenzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-carbamic acid benzyl ester (1.00 equiv.) was dissolved in ethanol (30 mL). The vessel in which resided the resulting solution was evacuated and backfilled with argon. A catalytic amount of Palladium on Carbon (10%, 0.10 equiv. by wt.) was added. T...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether
Primary amine
c1ccccc1
null
c1ccccc1.c1ccc2c(c1)CCC[NH]2
HO-
[Pd].C(C)O
null
4
COc1ccc(C(=O)N2c3ccccc3[C@H](NC(=O)OCc3ccccc3)C[C@@H]2C)cc1>[Pd].C(C)O>COc1ccc(C(=O)N2c3ccccc3[C@H](N)C[C@@H]2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ff4d180ba80a482b9e5386c5819c5170
COc1ccc(C(=O)N2c3ccccc3[C@H](N)C[C@@H]2C)cc1.O=[N+]([O-])c1ccc(B(O)O)cc1>>COc1ccc(C(=O)N2c3ccccc3[C@H](Nc3ccc([N+](=O)[O-])cc3)C[C@@H]2C)cc1
C(C)(=O)OCC.N[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)OC)C.[N+](=O)([O-])C1=CC=C(C=C1)B(O)O.N1=CC=CC=C1>>COC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)NC1=CC=C(C=C1)[N+](=O)[O-])C
[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[N:9]2[c:10]3[cH:11][cH:12][cH:13][cH:14][c:15]3[C@H:16]([NH2:17])[CH2:27][C@@H:28]2[CH3:29])[cH:30][cH:31]1.OB(O)[c:18]1[cH:19][cH:20][c:21]([N+:22](=[O:23])[O-:24])[cH:25][cH:26]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[N:9]2[c:10]3[cH:11][cH:12][cH:13][cH:1...
COc1ccc(C(=O)N2c3ccccc3[C@H](N)C[C@@H]2C)cc1.O=[N+]([O-])c1ccc(B(O)O)cc1
COc1ccc(C(=O)N2c3ccccc3[C@H](Nc3ccc([N+](=O)[O-])cc3)C[C@@H]2C)cc1
null
C(C)(=O)[O-].[Cu+2].C(C)(=O)[O-]
CN(C)C=O
Functional Group Addition
Petasis reaction with amines and boronic acids
f3a3deec78a4c59ad4805bc1bc7e2afd5094c4db08eb97c040b7aa35f49e0111
9ffbcc2fa72eea0571f83107c67a8772758cc82f1a93d93731e05645a35157fb
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
O-B(-O)-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C:6]-[C:7](-[NH2;D1;+0:8])-[c:9]>>[C:6]-[C:7](-[NH;D2;+0:8]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5])-[c:9]
null
[]
60
CELSIUS
1
HOUR
To a solution of (2S,4R)-(4-amino-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-(4-methoxy-phenyl)-methanone (1.00 equiv.) in DMF was added 4-nitrophenylboronic acid (2.00 equiv.), pyridine (2.50 equiv.) and copper(II)acetate (2.00 equiv.). The heterogeneous green mixture was stirred open to air for 1 h and then warmed to 60°...
10.6084/m9.figshare.5104873.v1
null
Primary amine.Boronic acid
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HO-.B
C(C)(=O)[O-].[Cu+2].C(C)(=O)[O-].CN(C)C=O
60
1
COc1ccc(C(=O)N2c3ccccc3[C@H](N)C[C@@H]2C)cc1.O=[N+]([O-])c1ccc(B(O)O)cc1>C(C)(=O)[O-].[Cu+2].C(C)(=O)[O-].CN(C)C=O>COc1ccc(C(=O)N2c3ccccc3[C@H](Nc3ccc([N+](=O)[O-])cc3)C[C@@H]2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4f823a42c0e84cbf9a59d53103631673
CC(=O)Cl.COc1ccc(C(=O)N2c3ccccc3[C@H](Nc3ccc([N+](=O)[O-])cc3)C[C@@H]2C)cc1>>COc1ccc(C(=O)N2c3ccccc3C(N(C(C)=O)c3ccc([N+](=O)[O-])cc3)CC2C)cc1
C(C)(=O)Cl.[N+](=O)([O-])C1=CC=C(C=C1)N[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)OC)C.C(C)(C)N(CC)C(C)C>>[N+](=O)([O-])C1=CC=C(C=C1)N(C(C)=O)C1CC(N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C
Cl[C:18]([CH3:19])=[O:20].[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[N:9]2[c:10]3[cH:11][cH:12][cH:13][cH:14][c:15]3[C@H:16]([NH:17][c:21]3[cH:22][cH:23][c:24]([N+:25](=[O:26])[O-:27])[cH:28][cH:29]3)[CH2:30][C@@H:31]2[CH3:32])[cH:33][cH:34]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[N:9]2[c:10]3[cH:11]...
CC(=O)Cl.COc1ccc(C(=O)N2c3ccccc3[C@H](Nc3ccc([N+](=O)[O-])cc3)C[C@@H]2C)cc1
COc1ccc(C(=O)N2c3ccccc3C(N(C(C)=O)c3ccc([N+](=O)[O-])cc3)CC2C)cc1
null
null
C(Cl)Cl
Acylation
N-alkylation of secondary amines with alkyl halides
b92e0bfd3d683c1f2a209adfe70a67ad7cb0d87749eb59e8fe0cf1689bc291e0
96cb0a2fed10552c5770a45a2d6523b47ac3e38928b4a9c698d8577451182dcd
O=C(c1ccccc1)N1CCC(Nc2ccccc2)c2ccccc21
Cl-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[c:4]:[c:5]1:[c:6]-[#7:7]-[C:8]-[C:9]-[C@H;D3;+0:10]-1-[NH;D2;+0:11]-[c:12](:[c:13]):[c:14]>>[C;D1;H3:2]-[C;H0;D3;+0:1](=[O;D1;H0:3])-[N;H0;D3;+0:11](-[CH;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[c:6]:[c:5]-1:[c:4])-[c:12](:[c:13]):[c:14]
null
[]
null
null
48
HOUR
To a solution of (2S,4R)-[4-(4-nitro-phenylamino)-2-methyl-3,4-dihydro-2H-quinolin-1-yl]-(4-methoxy-phenyl)-methanone (1.00 equiv.) in methylene chloride was added diisopropylethylamine (1.05 equiv) followed by acetyl chloride (1.00 equiv). The mixture was stirred at rt 48 h. The mixture was concentrated under reduced ...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Secondary amine
Tertiary amide
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HCl
C(Cl)Cl
null
48
CC(=O)Cl.COc1ccc(C(=O)N2c3ccccc3[C@H](Nc3ccc([N+](=O)[O-])cc3)C[C@@H]2C)cc1>C(Cl)Cl>COc1ccc(C(=O)N2c3ccccc3C(N(C(C)=O)c3ccc([N+](=O)[O-])cc3)CC2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-488ed7ba3be84fecb01dc4ac52382e51
COC1CCC(OC)O1.COc1ccc(C(=O)N2c3ccccc3C(N(C(C)=O)c3ccc(N)cc3)CC2C)cc1>>COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(-n4cccc4)cc3)C[C@@H]2C)cc1
COC1OC(CC1)OC.NC1=CC=C(C=C1)N(C(C)=O)C1CC(N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C.OS(=O)(=O)O.NC1=CC=CC=C1.C(=O)(O)[O-].[Na+]>>COC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=C(C=C2)N2C=CC=C2)C)C=C1
CO[CH:26]1O[CH:29](OC)[CH2:28][CH2:27]1.[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[N:9]2[c:10]3[cH:11][cH:12][cH:13][cH:14][c:15]3[CH:16]([N:17]([C:18]([CH3:19])=[O:20])[c:21]3[cH:22][cH:23][c:24]([NH2:25])[cH:30][cH:31]3)[CH2:32][CH:33]2[CH3:34])[cH:35][cH:36]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])...
COC1CCC(OC)O1.COc1ccc(C(=O)N2c3ccccc3C(N(C(C)=O)c3ccc(N)cc3)CC2C)cc1
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(-n4cccc4)cc3)C[C@@H]2C)cc1
null
null
CO.C1CCOC1
Aromatic Heterocycle Formation
OtherReaction
0e9d22b0723ec2930c6f0b28cb06c2d86835df697b962917265b2a52889a76e9
37da407ba22aeb87f9320448e7710117027e549cd7c89e722598c54789c5481f
O=C(c1ccccc1)N1CC[C@@H](Nc2ccc(-n3cccc3)cc2)c2ccccc21
C-O-[CH;D3;+0:1]1-O-[CH;D3;+0:2](-O-C)-[CH2;D2;+0:3]-[CH2;D2;+0:4]-1.[NH2;D1;+0:5]-[c;H0;D3;+0:6](:[c:7]:[c:8]):[c:9]:[c:10]>>[c:8]:[c:7]:[c;H0;D3;+0:6](-[n;H0;D3;+0:5]1:[cH;D2;+0:1]:[cH;D2;+0:4]:[cH;D2;+0:3]:[cH;D2;+0:2]:1):[c:9]:[c:10]
null
[]
null
null
null
null
N-(4-amino-phenyl)-N-[1-(4-methoxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide (22 mg, 0.05 mmol) was dissolved in MeOH:THF (1 mL each) and cooled to 10° C. 2,5-dimethoxy-tetrahydrofuran (1.25 equiv.) was dissolved in THF and catalytic H2SO4, and added drop wise to the aniline mixture. The mixture was...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether.Ether.Primary amine
null
C1CCOC1
c1cc[nH]c1
c1ccccc1.c1ccccc1.c1cc[nH]c1.c1ccc2c(c1)CCC[NH]2
HO-
CO.C1CCOC1
null
null
COC1CCC(OC)O1.COc1ccc(C(=O)N2c3ccccc3C(N(C(C)=O)c3ccc(N)cc3)CC2C)cc1>CO.C1CCOC1>COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(-n4cccc4)cc3)C[C@@H]2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ec0d7d1729e94e1391dec2cf72e75ddf
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccncc3)C[C@@H]2C)cc1>>COc1ccc(C(=O)N2c3ccccc3[C@H](N)C[C@@H]2C)cc1
COC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=NC=C2)C)C=C1.FC1=CC=C(C(=O)Cl)C=C1>>COC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N)C)C=C1
CC(=O)[N:17](c1ccncc1)[C@H:16]1[c:15]2[c:10]([cH:11][cH:12][cH:13][cH:14]2)[N:9]([C:7]([c:6]2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:22][cH:21]2)=[O:8])[C@@H:19]([CH3:20])[CH2:18]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[N:9]2[c:10]3[cH:11][cH:12][cH:13][cH:14][c:15]3[C@H:16]([NH2:17])[CH2:18][C@@H:19]2[CH3:20])[...
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccncc3)C[C@@H]2C)cc1
COc1ccc(C(=O)N2c3ccccc3[C@H](N)C[C@@H]2C)cc1
null
null
null
Reduction
OtherReaction
76fc567d17af101afc4274920efc47186f371dc83cc33bd4c146b365ec4fe29d
b6ecdf8828e00ae514386eea0ddddd5ef4b4a45a73b1f3e69d39008dedb0e977
O=C(c1ccccc1)N1CCCc2ccccc21
C-C(=O)-[N;H0;D3;+0:1](-[C:2](-[C:3])-[c:4])-c1:c:c:n:c:c:1>>[C:3]-[C:2](-[NH2;D1;+0:1])-[c:4]
null
[]
null
null
null
null
N-[(2S,4R)-1-(4-methoxybenzoyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl]-N-pyridin-4-ylacetamide was made following general procedure G, substituting 4-methoxybenzoyl chloride for 4-fluorobenzoyl chloride. The amine-aryl coupling was performed differently to what is described in procedure G. Therefore (2S,4R)-1-(4-met...
10.6084/m9.figshare.5104873.v1
null
Tertiary amide
Primary amine
c1ccncc1
null
c1ccccc1.c1ccc2c(c1)CCC[NH]2
HO-
null
null
null
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccncc3)C[C@@H]2C)cc1>>COc1ccc(C(=O)N2c3ccccc3[C@H](N)C[C@@H]2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1d093cc2a53448c3806da023214b521f
CC(=O)Cl.COc1ccc(C(=O)N2c3ccccc3[C@H](Nc3ccncc3)C[C@@H]2C)cc1>>COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccncc3)C[C@@H]2C)cc1
C(C)(=O)Cl.COC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)NC2=CC=NC=C2)C)C=C1.C(C)(C)N(CC)C(C)C>>COC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=NC=C2)C)C=C1
Cl[C:18]([CH3:19])=[O:20].[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[N:9]2[c:10]3[cH:11][cH:12][cH:13][cH:14][c:15]3[C@H:16]([NH:17][c:21]3[cH:22][cH:23][n:24][cH:25][cH:26]3)[CH2:27][C@@H:28]2[CH3:29])[cH:30][cH:31]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[N:9]2[c:10]3[cH:11][cH:12][cH:13][cH:14][c:1...
CC(=O)Cl.COc1ccc(C(=O)N2c3ccccc3[C@H](Nc3ccncc3)C[C@@H]2C)cc1
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccncc3)C[C@@H]2C)cc1
null
null
C(Cl)Cl
Acylation
N-alkylation of secondary amines with alkyl halides
b92e0bfd3d683c1f2a209adfe70a67ad7cb0d87749eb59e8fe0cf1689bc291e0
96cb0a2fed10552c5770a45a2d6523b47ac3e38928b4a9c698d8577451182dcd
O=C(c1ccccc1)N1CC[C@@H](Nc2ccncc2)c2ccccc21
Cl-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[C:4]-[C:5](-[NH;D2;+0:6]-[c:7]1:[c:8]:[c:9]:[#7;a:10]:[c:11]:[c:12]:1)-[c:13]>>[C:4]-[C:5](-[N;H0;D3;+0:6](-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3])-[c:7]1:[c:8]:[c:9]:[#7;a:10]:[c:11]:[c:12]:1)-[c:13]
61
[{"value": 61.0, "product": "COC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=NC=C2)C)C=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 60.2, "product": "COC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=NC=C2)C)C=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
To a solution of (2S,4R)-1-(4-methoxybenzoyl)-2-methyl-N-pyridin-4-yl-1,2,3,4-tetrahydroquinolin-4-amine (90 mg, 0.24 mmol, 1 equ.) in methylene chloride (0.8 mL) was added diisopropylethylamine (84 uL, 0.48 mmol, 2 equ.) followed by acetyl chloride (340 uL, 4.80 mmol, 20 equ.). The mixture was stirred at room temperat...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Secondary amine
Tertiary amide
null
null
c1ccccc1.c1ccncc1.c1ccc2c(c1)CCC[NH]2
HCl
C(Cl)Cl
null
2
CC(=O)Cl.COc1ccc(C(=O)N2c3ccccc3[C@H](Nc3ccncc3)C[C@@H]2C)cc1>C(Cl)Cl>COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccncc3)C[C@@H]2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8a36c0fdeba94a5583f46b1c5c60c01f
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3C)C[C@@H]2C)cc1>>COc1ccc(C(=O)N2c3ccccc3[C@H](N)C[C@@H]2C)cc1
ClC1=CC(=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C)C.FC1=CC=C(C(=O)Cl)C=C1>>COC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N)C)C=C1
CC(=O)[N:17](c1ccc(Cl)cc1C)[C@H:16]1[c:15]2[c:10]([cH:11][cH:12][cH:13][cH:14]2)[N:9]([C:7]([c:6]2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:22][cH:21]2)=[O:8])[C@@H:19]([CH3:20])[CH2:18]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[N:9]2[c:10]3[cH:11][cH:12][cH:13][cH:14][c:15]3[C@H:16]([NH2:17])[CH2:18][C@@H:19]2[CH3:...
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3C)C[C@@H]2C)cc1
COc1ccc(C(=O)N2c3ccccc3[C@H](N)C[C@@H]2C)cc1
null
null
null
Reduction
OtherReaction
69ade7084af88ddffae90deb44c09e0c476b222fcdeb2da3e52886d1c22e74d7
2e45e9423fbaf161029375476baedc687fb5d07b407064b643e17c8e77249ca5
O=C(c1ccccc1)N1CCCc2ccccc21
C-C(=O)-[N;H0;D3;+0:1](-[C:2](-[C:3])-[c:4])-c1:c:c:c(-Cl):c:c:1-C>>[C:3]-[C:2](-[NH2;D1;+0:1])-[c:4]
null
[]
null
null
null
null
N-(4-chloro-2-methylphenyl)-N-[(2S,4R)-1-(4-methoxybenzoyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl]acetamide was made following general procedure G, substituting 4-methoxybenzoyl chloride for 4-fluorobenzoyl chloride. The amine-aryl coupling was performed differently to what is described in procedure G. Therefore (2S...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Tertiary amide
Primary amine
c1ccccc1
null
c1ccccc1.c1ccc2c(c1)CCC[NH]2
HCl
null
null
null
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3C)C[C@@H]2C)cc1>>COc1ccc(C(=O)N2c3ccccc3[C@H](N)C[C@@H]2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-03d9916989184068b80e32df42f4744c
CC(=O)Cl.COc1ccc(C(=O)N2c3ccccc3[C@H](Nc3ccc(Cl)cc3C)C[C@@H]2C)cc1>>COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3C)C[C@@H]2C)cc1
ClC1=CC(=C(C=C1)N[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C)C.C(C)(C)N(CC)C(C)C.C(C)(=O)Cl>>ClC1=CC(=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C)C
Cl[C:18]([CH3:19])=[O:20].[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[N:9]2[c:10]3[cH:11][cH:12][cH:13][cH:14][c:15]3[C@H:16]([NH:17][c:21]3[cH:22][cH:23][c:24]([Cl:25])[cH:26][c:27]3[CH3:28])[CH2:29][C@@H:30]2[CH3:31])[cH:32][cH:33]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[N:9]2[c:10]3[cH:11][cH:12][c...
CC(=O)Cl.COc1ccc(C(=O)N2c3ccccc3[C@H](Nc3ccc(Cl)cc3C)C[C@@H]2C)cc1
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3C)C[C@@H]2C)cc1
null
null
null
Acylation
N-alkylation of secondary amines with alkyl halides
b92e0bfd3d683c1f2a209adfe70a67ad7cb0d87749eb59e8fe0cf1689bc291e0
96cb0a2fed10552c5770a45a2d6523b47ac3e38928b4a9c698d8577451182dcd
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Cl-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[C:4]-[C:5](-[NH;D2;+0:6]-[c:7](:[c:8]):[c:9])-[c:10]>>[C:4]-[C:5](-[N;H0;D3;+0:6](-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3])-[c:7](:[c:8]):[c:9])-[c:10]
92
[{"value": 92.0, "product": "ClC1=CC(=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
5
HOUR
To a solution of (2S,4R)-N-(4-chloro-2-methylphenyl)-1-(4-methoxybenzoyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-amine (140 mg, 0.33 mmol, 1 equ.) in acetyl chloride (1.0 mL) was added diisopropylethylamine (58 uL, 0.33 mmol, 1 equ.). The mixture was stirred at room temperature for 5 h. The mixture was concentrated unde...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Secondary amine
Tertiary amide
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HCl
null
null
5
CC(=O)Cl.COc1ccc(C(=O)N2c3ccccc3[C@H](Nc3ccc(Cl)cc3C)C[C@@H]2C)cc1>>COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3C)C[C@@H]2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5398365646f94010a1d6ec6a5b5c7211
CC(=O)Cl.C[C@H]1C[C@@H](Nc2ccc(Cl)cc2)c2ccccc2N1C(=O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)c2ccccc21
FC(C=1C=C(C=C(C1)C(F)(F)F)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)NC1=CC=C(C=C1)Cl)C)(F)F.C(C)(=O)Cl.C(C)N(CC)CC.C(Cl)Cl>>FC(C=1C=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=C(C=C2)Cl)C)C=C(C1)C(F)(F)F)(F)F
Cl[C:2]([CH3:1])=[O:3].[NH:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][c:21]([C:22]([F:23])([F:24])[F:25])[cH:26][c:27]([C:28]([F:29])([F:30])[F:31])[cH:32]2)[c:33]2[cH:34][cH:35][cH:36][cH:37][c:38]21>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6]...
CC(=O)Cl.C[C@H]1C[C@@H](Nc2ccc(Cl)cc2)c2ccccc2N1C(=O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)c2ccccc21
null
null
null
Acylation
N-alkylation of secondary amines with alkyl halides
b92e0bfd3d683c1f2a209adfe70a67ad7cb0d87749eb59e8fe0cf1689bc291e0
96cb0a2fed10552c5770a45a2d6523b47ac3e38928b4a9c698d8577451182dcd
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Cl-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[C:4]-[C:5](-[NH;D2;+0:6]-[c:7](:[c:8]):[c:9])-[c:10]>>[C:4]-[C:5](-[N;H0;D3;+0:6](-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3])-[c:7](:[c:8]):[c:9])-[c:10]
86
[{"value": 86.0, "product": "FC(C=1C=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=C(C=C2)Cl)C)C=C(C1)C(F)(F)F)(F)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
A solution of (3,5-bis(trifluoromethyl)phenyl)((2S,4R)-4-(4-chlorophenylamino)-2-methyl-3,4-dihydroquinolin-1(2H)-yl)methanone (19.44 g, 0.037 mol) in acetyl chloride (5 mL) was cooled to 0° C. and triethylamine (6.59 mL, 0.037 mol) was added dropwise over 30 min, a precipitate forms during this time. An additional 250...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Secondary amine
Tertiary amide
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HCl
null
null
8
CC(=O)Cl.C[C@H]1C[C@@H](Nc2ccc(Cl)cc2)c2ccccc2N1C(=O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7429fc6ca7b44e1ba04bd99200e259bc
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(NCCC(=O)O)cc2)c2ccccc21.[NH4+]>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(NCCC(N)=O)cc2)c2ccccc21
[Cl-].[NH4+].C=1C=CC2=C(C1)N=NN2O.CN(C)C(=[N+](C)C)ON1C2=C(C=CC=N2)N=N1.F[P-](F)(F)(F)(F)F.C(C)(C)N(CC)C(C)C.C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)NCCC(=O)O)C)C1=CC=C(C=C1)Cl>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)NCCC(=O)N)C)C1=CC=C(C=C1)Cl
O[C:26]([CH2:25][CH2:24][NH:23][c:22]1[cH:21][cH:20][c:19]([C:17]([N:16]2[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]3[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]3)[c:36]3[c:31]2[cH:32][cH:33][cH:34][cH:35]3)=[O:18])[cH:30][cH:29]1)=[O:28].[NH4+:27]>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(NCCC(=O)O)cc2)c2ccccc21.[NH4+]
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(NCCC(N)=O)cc2)c2ccccc21
null
null
CN(C)C=O.C(C)(=O)OCC
Acylation
Carboxylic acid to amide conversion
1283aef55d7ee699f097a8e5267689198c76ba671644401547f902657820236d
cb0a71c3fb37a76e96fbd81aae6f95a28398a03d1ad2c8e877085e735efb98f1
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[C:4].[NH4+;D0:5]>>[C:4]-[C:3]-[C;H0;D3;+0:1](-[NH2;D1;+0:5])=[O;D1;H0:2]
null
[]
null
null
18
HOUR
(2S,4R)-3-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenylamino)-propionamide was prepared from (2S,4R)-3-(4-{4-[acetyl(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenylamino)-propionic acid. The acid (0.060 g, 0.118 mmol) was dissolved in DMF (1.5 m...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
Primary amide
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HO-
CN(C)C=O.C(C)(=O)OCC
null
18
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(NCCC(=O)O)cc2)c2ccccc21.[NH4+]>CN(C)C=O.C(C)(=O)OCC>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(NCCC(N)=O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-cb467bc9a786406ab8d272b646b1c508
COC(=O)C(C)(C)CCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1F>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)c(F)c2)c2ccccc21
C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC(=C(OCCC(C(=O)OC)(C)C)C=C1)F)C)C1=CC=C(C=C1)Cl.[Li+].[OH-]>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC(=C(OCCC(C(=O)O)(C)C)C=C1)F)C)C1=CC=C(C=C1)Cl
C[O:31][C:29]([C:26]([CH2:25][CH2:24][O:23][c:22]1[cH:21][cH:20][c:19]([C:17]([N:16]2[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]3[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]3)[c:40]3[c:35]2[cH:36][cH:37][cH:38][cH:39]3)=[O:18])[cH:34][c:32]1[F:33])([CH3:27])[CH3:28])=[O:30]>>[CH3:1][C:2](=[O:3])[N:...
COC(=O)C(C)(C)CCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1F
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)c(F)c2)c2ccccc21
null
null
CO.C1CCOC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
70.5
[{"value": 70.0, "product": "C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC(=C(OCCC(C(=O)O)(C)C)C=C1)F)C)C1=CC=C(C=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 70.5, "product": "C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC(=C(OCCC(C(=O)O)(C)C)C=C1)F)C)C1=CC=C(C=C1)Cl", "details": "CALCUL...
null
null
8
HOUR
To the solution of methyl 4-(4-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}-2-fluorophenoxy)-2,2-dimethylbutanoate (176 mg, 0.30 mmol) in MeOH/THF (1 mL/1 mL) was added excessive LiOH (1N aqueous solution). The reaction mixture was stirred at r.t. overnight. The reaction was...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
Other
CO.C1CCOC1
null
8
COC(=O)C(C)(C)CCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1F>CO.C1CCOC1>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)c(F)c2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9dd67dbf49b0479e84dc553da0a6f407
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.CCOC(=O)C(F)Br>>CCOC(=O)[C@H](F)Oc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)CC2C)cc1
ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)O)=O)C.C(=O)([O-])[O-].[Cs+].[Cs+].C(C)OC(C(F)Br)=O>>C(C)OC([C@H](F)OC1=CC=C(C=C1)C(=O)N1C(C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C)=O
[OH:8][c:9]1[cH:10][cH:11][c:12]([C:13](=[O:14])[N:15]2[c:16]3[cH:17][cH:18][cH:19][cH:20][c:21]3[C@H:22]([N:23]([C:24]([CH3:25])=[O:26])[c:27]3[cH:28][cH:29][c:30]([Cl:31])[cH:32][cH:33]3)[CH2:34][C@@H:35]2[CH3:36])[cH:37][cH:38]1.Br[CH:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[F:7]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[C@H:6]...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.CCOC(=O)C(F)Br
CCOC(=O)[C@H](F)Oc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)CC2C)cc1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
b4a5d39314a5c443cda9b2e0e236243ac442dfde1252cc812738ea1c57498207
6a03f897cefed753ca7beb47f7ee547f94bbaa026873cf266e2d9e7227c9679e
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Br-[CH;D3;+0:1](-[F;D1;H0:2])-[C:3](=[O;D1;H0:4])-[#8:5]-[C:6].[OH;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[C:6]-[#8:5]-[C:3](=[O;D1;H0:4])-[C@H;D3;+0:1](-[F;D1;H0:2])-[O;H0;D2;+0:7]-[c:8](:[c:9]):[c:10]
null
[]
null
null
8
HOUR
(2S,4R)-N-(4-Chloro-phenyl)-N-[1-(4-hydroxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide (202 mg, 0.46 mmol) was dissolved in DMF (2 mL) at room temperature. Cs2CO3 (760 mg, 2.33 mmol) was added followed by bromo-fluoro-acetic acid ethyl ester (0.070 mL, 0.583 mmol) and the reaction was allowed to stir...
10.6084/m9.figshare.5104873.v1
null
Secondary halide.Secondary halide.Ester.Aromatic alcohol
Secondary halide.Ester.Ether
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HBr
CN(C)C=O
null
8
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.CCOC(=O)C(F)Br>CN(C)C=O>CCOC(=O)[C@H](F)Oc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)CC2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7763ed6ac07849ec84896e5dafb72433
COC(=O)C(C)(C)CCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)C(C)C)c3ccc(Cl)cc3)C[C@@H]2C)cc1>>CC(C)C(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)cc2)c2ccccc21
ClC1=CC=C(C=C1)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCCC(C(=O)OC)(C)C)C=C1)C)C(C(C)C)=O.[OH-].[Na+]>>ClC1=CC=C(C=C1)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCCC(C(=O)O)(C)C)C=C1)C)C(C(C)C)=O
C[O:33][C:31]([C:28]([CH2:27][CH2:26][O:25][c:24]1[cH:23][cH:22][c:21]([C:19]([N:18]2[C@@H:16]([CH3:17])[CH2:15][C@@H:14]([N:6]([C:4]([CH:2]([CH3:1])[CH3:3])=[O:5])[c:7]3[cH:8][cH:9][c:10]([Cl:11])[cH:12][cH:13]3)[c:41]3[c:36]2[cH:37][cH:38][cH:39][cH:40]3)=[O:20])[cH:35][cH:34]1)([CH3:29])[CH3:30])=[O:32]>>[CH3:1][CH:...
COC(=O)C(C)(C)CCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)C(C)C)c3ccc(Cl)cc3)C[C@@H]2C)cc1
CC(C)C(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)cc2)c2ccccc21
null
null
CO.O1CCCC1.O
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
null
[]
40
CELSIUS
8
HOUR
Methyl 4-(4-{[(2S,4R)-4-[(4-chlorophenyl)(isobutyryl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}phenoxy)-2,2-dimethylbutanoate was dissolved in methanol/tetrahydrofuran/water (2/1/1) then sodium hydroxide (3 equivalents) was added and reaction mixture stirred at 40° C. overnight. The mixture was concentrated...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
Other
CO.O1CCCC1.O
40
8
COC(=O)C(C)(C)CCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)C(C)C)c3ccc(Cl)cc3)C[C@@H]2C)cc1>CO.O1CCCC1.O>CC(C)C(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-114dec0569914f41baf939b57f2aa16f
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN)cc2)c2ccccc21.CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN)cc2)c2ccccc21.CCOC(=O)C(C)(C)Br.O=C([O-])[O-]>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCNCC(=O)O)cc2)c2ccccc21.CCOC(=O)CNCCCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]...
NCCCOC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=C(C=C2)Cl)C)C=C1.NCCCOC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=C(C=C2)Cl)C)C=C1.BrC(C(=O)OCC)(C)C.C([O-])([O-])=O.[K+].[K+]>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCCCNCC(=O)O)C=C1)C)C1=CC=C(C=C1)Cl.C(C)OC(CNCCCOC1=CC=C(C=C1)C(=O...
[NH2:46][CH2:47][CH2:48][CH2:49][O:50][c:51]1[cH:52][cH:53][c:54]([C:55](=[O:56])[N:57]2[c:58]3[cH:59][cH:60][cH:61][cH:62][c:63]3[C@H:64]([N:65]([C:66]([CH3:67])=[O:68])[c:69]3[cH:70][cH:71][c:72]([Cl:73])[cH:74][cH:75]3)[CH2:76][C@@H:77]2[CH3:78])[cH:79][cH:80]1.[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN)cc2)c2ccccc21.CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN)cc2)c2ccccc21.CCOC(=O)C(C)(C)Br.O=C([O-])[O-]
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCNCC(=O)O)cc2)c2ccccc21.CCOC(=O)CNCCCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
null
null
CN(C=O)C
C-C Coupling
OtherReaction
85ce140ed7df019d78749a483fc7030af41431c1c32010e1ce1fdf480af5ee36
baad18433170eb92a62d67bae9e800b7ec6b2c9b09d470edf2e3a10a60cf5177
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21.O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Br-[C;H0;D4;+0:1](-C)(-[CH3;D1;+0:2])-[C:3](=[O;D1;H0:4])-[#8:5]-[C:6].[C:7]-[C:8]-[NH2;D1;+0:9].[C:10]-[C:11]-[NH2;D1;+0:12].[O-;H0;D1:13]-[C;H0;D3;+0:14](-[O-])=[O;D1;H0:15]>>[C:6]-[#8:5]-[C:3](=[O;D1;H0:4])-[CH2;D2;+0:1]-[NH;D2;+0:9]-[C:8]-[C:7].[C:10]-[C:11]-[NH;D2;+0:12]-[CH2;D2;+0:2]-[C;H0;D3;+0:14](=[O;D1;H0:15]...
12
[{"value": 12.0, "product": "C(C)OC(CNCCCOC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C)=O", "details": "PERCENTYIELD", "is_desired": false}]
50
CELSIUS
null
null
{[3-(4-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}phenoxy)propyl]amino}acetic acid was prepared from (2S,4R)-N-{1-[4-(3-amino-propoxy)-benzoyl]-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl}-N-(4-chloro-phenyl)-acetamide. (2S,4R)-N-{1-[4-(3-amino-propoxy)-benzoyl]-2-methyl-1,2,...
10.6084/m9.figshare.5104873.v1
null
Tertiary halide.Ester.Primary amine.Primary amine
Carboxylic acid.Ester.Secondary amine.Secondary amine
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2.c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HBr
CN(C=O)C
50
null
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN)cc2)c2ccccc21.CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN)cc2)c2ccccc21.CCOC(=O)C(C)(C)Br.O=C([O-])[O-]>CN(C=O)C>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCNCC(=O)O)cc2)c2ccccc21.CCOC(=O)CNCCCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3...
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-0862fb5a6db144608d6618f49de238b1
CCOC(=O)CNCCCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCNCC(=O)O)cc2)c2ccccc21
C(C)OC(CNCCCOC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C)=O.C(C)O.[OH-].[Na+]>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCCCNCC(=O)O)C=C1)C)C1=CC=C(C=C1)Cl
CC[O:31][C:29]([CH2:28][NH:27][CH2:26][CH2:25][CH2:24][O:23][c:22]1[cH:21][cH:20][c:19]([C:17]([N:16]2[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]3[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]3)[c:39]3[c:34]2[cH:35][cH:36][cH:37][cH:38]3)=[O:18])[cH:33][cH:32]1)=[O:30]>>[CH3:1][C:2](=[O:3])[N:4]([c:5...
CCOC(=O)CNCCCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCNCC(=O)O)cc2)c2ccccc21
null
null
O1CCCC1
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
75
[{"value": 75.0, "product": "C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCCCNCC(=O)O)C=C1)C)C1=CC=C(C=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
{[3-(4-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}phenoxy)propyl]amino}acetic ethyl ester was hydrolyzed to the acid by dissolving in tetrahydrofuran and ethanol and sodium hydroxide (1N) was added. The mixture was stirred at room temperature overnight. The mixture was cool...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
Other
O1CCCC1
null
8
CCOC(=O)CNCCCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1>O1CCCC1>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCNCC(=O)O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3573696cebef47f8b539e4cb7f4aa5bc
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OC3CCC(C(=O)O)CC3)cc2)c2ccccc21.[NH4+]>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OC3CCC(C(N)=O)CC3)cc2)c2ccccc21
C1CCOC1.C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OC2CCC(CC2)C(=O)O)C=C1)C)C1=CC=C(C=C1)Cl.C=1C=CC2=C(C1)N=NN2O.CCN=C=NCCCN(C)C.[Cl-].[NH4+]>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OC2CCC(CC2)C(=O)N)C=C1)C)C1=CC=C(C=C1)Cl
O[C:28]([CH:27]1[CH2:26][CH2:25][CH:24]([O:23][c:22]2[cH:21][cH:20][c:19]([C:17]([N:16]3[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]4[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]4)[c:40]4[c:35]3[cH:36][cH:37][cH:38][cH:39]4)=[O:18])[cH:34][cH:33]2)[CH2:32][CH2:31]1)=[O:30].[NH4+:29]>>[CH3:1][C:2](=[O...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OC3CCC(C(=O)O)CC3)cc2)c2ccccc21.[NH4+]
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OC3CCC(C(N)=O)CC3)cc2)c2ccccc21
null
CN(C)C=O
C(C)(=O)OCC
Acylation
Carboxylic acid to amide conversion
1283aef55d7ee699f097a8e5267689198c76ba671644401547f902657820236d
cb0a71c3fb37a76e96fbd81aae6f95a28398a03d1ad2c8e877085e735efb98f1
O=C(c1ccc(OC2CCCCC2)cc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])-[C:5].[NH4+;D0:6]>>[C:4]-[C:3](-[C;H0;D3;+0:1](-[NH2;D1;+0:6])=[O;D1;H0:2])-[C:5]
71
[{"value": 71.0, "product": "C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OC2CCC(CC2)C(=O)N)C=C1)C)C1=CC=C(C=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}]
null
null
11
HOUR
(2S,4R)-4-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-cyclohexanecarboxylic acid (0.070 g, 0.125 mmol) was converted to the amide by dissolving in THF (1 mL) at room temperature. HOBt (0.025 g), EDCI (0.035 g), and ammonium chloride (0.014 g, 0.25 mmol) was added along ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
Primary amide
null
null
c1ccccc1.c1ccccc1.C1CCCCC1.c1ccc2c(c1)CCC[NH]2
HO-
CN(C)C=O.C(C)(=O)OCC
null
11
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OC3CCC(C(=O)O)CC3)cc2)c2ccccc21.[NH4+]>CN(C)C=O.C(C)(=O)OCC>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OC3CCC(C(N)=O)CC3)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a3e433dfc78b40fab5037762e0988ff9
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)C3CC3)c3ccc(Cl)cc3)C[C@@H]2C)cc1>>C[C@H]1C[C@@H](N(C(=O)C2CC2)c2ccc(Cl)cc2)c2ccccc2N1C(=O)c1ccc(O)cc1
ClC1=CC=C(C=C1)N(C(=O)C1CC1)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C.B(Br)(Br)Br>>ClC1=CC=C(C=C1)N(C(=O)C1CC1)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)O)=O)C
C[O:31][c:30]1[cH:29][cH:28][c:27]([C:25]([N:24]2[C@@H:2]([CH3:1])[CH2:3][C@@H:4]([N:5]([C:6](=[O:7])[CH:8]3[CH2:9][CH2:10]3)[c:11]3[cH:12][cH:13][c:14]([Cl:15])[cH:16][cH:17]3)[c:18]3[cH:19][cH:20][cH:21][cH:22][c:23]32)=[O:26])[cH:33][cH:32]1>>[CH3:1][C@H:2]1[CH2:3][C@@H:4]([N:5]([C:6](=[O:7])[CH:8]2[CH2:9][CH2:10]2)...
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)C3CC3)c3ccc(Cl)cc3)C[C@@H]2C)cc1
C[C@H]1C[C@@H](N(C(=O)C2CC2)c2ccc(Cl)cc2)c2ccccc2N1C(=O)c1ccc(O)cc1
null
null
C(Cl)Cl
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
O=C(c1ccccc1)N1CC[C@@H](N(C(=O)C2CC2)c2ccccc2)c2ccccc21
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[OH;D1;+0:1]-[c:2](:[c:3]):[c:4]
98.1
[{"value": 98.0, "product": "ClC1=CC=C(C=C1)N(C(=O)C1CC1)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)O)=O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 98.1, "product": "ClC1=CC=C(C=C1)N(C(=O)C1CC1)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)O)=O)C", "details": "CALCULATEDPERCENTYIELD", "is_desired":...
null
null
4
HOUR
To a solution of N-(4-chlorophenyl)-N-[(2S,4R)-1-(4-methoxybenzoyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl]cyclopropanecarboxamide (200 mg, 0.42 mmol, 1 equ.) in methylene chloride (0.3 mL) was added a 1 M solution of boron tribromide in methylene chloride (1.2 mL, 1.26 mmol, 3 equ.). The reaction mixture was stirred...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
C1CC1.c1ccccc1.c1ccc2c(c1)CCC[NH]2.c1ccccc1
Other
C(Cl)Cl
null
4
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)C3CC3)c3ccc(Cl)cc3)C[C@@H]2C)cc1>C(Cl)Cl>C[C@H]1C[C@@H](N(C(=O)C2CC2)c2ccc(Cl)cc2)c2ccccc2N1C(=O)c1ccc(O)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3ec990318aa842b0a8aa7d128b64c51a
C=CCC(C)(C)C(=O)OC.COC(=O)C1=CC=CC(F)(Br)C1>>COC(=O)c1ccc(/C=C/CC(C)(C)C(=O)OC)c(F)c1
COC(C=1CC(C=CC1)(F)Br)=O.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C(C)(=O)[O-].[K+].CC(C(=O)OC)(CC=C)C>>FC=1C=C(C(=O)OC)C=CC1\C=C\CC(C(=O)OC)(C)C
[CH2:9]=[CH:10][CH2:11][C:12]([CH3:13])([CH3:14])[C:15](=[O:16])[O:17][CH3:18].Br[C:19]1([F:20])[CH:8]=[CH:7][CH:6]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[CH2:21]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8](/[CH:9]=[CH:10]/[CH2:11][C:12]([CH3:13])([CH3:14])[C:15](=[O:16])[O:17][CH3:18])[c:19]([F:20])[cH:21]1
C=CCC(C)(C)C(=O)OC.COC(=O)C1=CC=CC(F)(Br)C1
COC(=O)c1ccc(/C=C/CC(C)(C)C(=O)OC)c(F)c1
null
[Cl-].C(CCC)[N+](CCCC)(CCCC)CCCC.C(C)(=O)[O-].[Pd+2].C(C)(=O)[O-]
CN(C=O)C
C-C Coupling
OtherReaction
cec44053563f2a43dba0cc3feeb46f2573d35c2009d333d4b42036f44d99070a
590a858358bdd7960af36d29559dbd36f713a74d9933580f6c1a28b7888836e0
c1ccccc1
Br-[C;H0;D4;+0:1]1(-[F;D1;H0:2])-[CH2;D2;+0:3]-[C;H0;D3;+0:4](-[C:5](=[O;D1;H0:6])-[#8:7]-[C;D1;H3:8])=[CH;D2;+0:9]-[CH;D2;+0:10]=[CH;D2;+0:11]-1.[C:12]-[C:13]=[CH2;D1;+0:14]>>[C:12]/[C:13]=[CH;D2;+0:14]/[c;H0;D3;+0:11]1:[cH;D2;+0:10]:[cH;D2;+0:9]:[c;H0;D3;+0:4](-[C:5](=[O;D1;H0:6])-[#8:7]-[C;D1;H3:8]):[cH;D2;+0:3]:[c;...
null
[]
130
CELSIUS
null
null
Methyl 5-(4-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydro1quinolin-1(2H)-yl]carbonyl}-2-fluorophenyl)-2,2-dimethylpentanoate was prepared following general procedure B, substituting methyl 5-[4-(chlorocarbonyl)-2-fluorophenyl]-2,2-dimethylpentanoate for 6-trifluoromethyl nicotinyl chloride. (Methyl 5-[...
10.6084/m9.figshare.5104873.v1
null
Tertiary halide.Tertiary halide.Ester.Allyl.Conjugated diene
Aromatic halide.Ester
C1=CCCC=C1
c1ccccc1
c1ccccc1
HBr
[Cl-].C(CCC)[N+](CCCC)(CCCC)CCCC.C(C)(=O)[O-].[Pd+2].C(C)(=O)[O-].CN(C=O)C
130
null
C=CCC(C)(C)C(=O)OC.COC(=O)C1=CC=CC(F)(Br)C1>[Cl-].C(CCC)[N+](CCCC)(CCCC)CCCC.C(C)(=O)[O-].[Pd+2].C(C)(=O)[O-].CN(C=O)C>COC(=O)c1ccc(/C=C/CC(C)(C)C(=O)OC)c(F)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d0f906a6f13d4c0ea7a866b804f4667e
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.CCOC(=O)C(C)(C)CCl>>CCOC(=O)C(C)(C)COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)O)=O)C.C(=O)([O-])[O-].[K+].[K+].C(C)OC(C(CCl)(C)C)=O>>C(C)OC(C(COC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C)(C)C)=O
[OH:10][c:11]1[cH:12][cH:13][c:14]([C:15](=[O:16])[N:17]2[c:18]3[cH:19][cH:20][cH:21][cH:22][c:23]3[C@H:24]([N:25]([C:26]([CH3:27])=[O:28])[c:29]3[cH:30][cH:31][c:32]([Cl:33])[cH:34][cH:35]3)[CH2:36][C@@H:37]2[CH3:38])[cH:39][cH:40]1.Cl[CH2:9][C:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])([CH3:7])[CH3:8]>>[CH3:1][CH2:2][O:3][...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.CCOC(=O)C(C)(C)CCl
CCOC(=O)C(C)(C)COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Cl-[CH2;D2;+0:1]-[C:2](-[C;D1;H3:3])(-[C;D1;H3:4])-[C:5](=[O;D1;H0:6])-[#8:7]-[C:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[C:8]-[#8:7]-[C:5](=[O;D1;H0:6])-[C:2](-[C;D1;H3:3])(-[C;D1;H3:4])-[CH2;D2;+0:1]-[O;H0;D2;+0:9]-[c:10](:[c:11]):[c:12]
32
[{"value": 32.0, "product": "C(C)OC(C(COC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C)(C)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 31.2, "product": "C(C)OC(C(COC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C)(C)C)=O", "details": "CALCULATEDPERC...
90
CELSIUS
null
null
(2S,4R)-N-(4-Chloro-phenyl)-N-[1-(4-hydroxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide (0.32 g, 0.74 mmol) was dissolved in 10 ml DMF at room temperature and K2CO3 (0.51 g, 3.7 mmol) was added. 3-Chloro-2,2-dimethyl-propionic acid ethyl ester (0.25 g, 1.52 mmol) was added and the reaction was allowed...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HCl
CN(C)C=O
90
null
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.CCOC(=O)C(C)(C)CCl>CN(C)C=O>CCOC(=O)C(C)(C)COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3f3cbef47fbf4db59ebe0ebb6442b3ed
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.O=S(=O)(O)CCCCl>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCS(=O)(=O)O)cc2)c2ccccc21
ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)O)=O)C.[H-].[Na+].ClCCCS(=O)(=O)O>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCCCS(=O)(=O)O)C=C1)C)C1=CC=C(C=C1)Cl
[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]([OH:23])[cH:31][cH:32]2)[c:33]2[cH:34][cH:35][cH:36][cH:37][c:38]21.Cl[CH2:24][CH2:25][CH2:26][S:27](=[O:28])(=[O:29])[OH:30]>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[c...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.O=S(=O)(O)CCCCl
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCS(=O)(=O)O)cc2)c2ccccc21
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Cl-[CH2;D2;+0:1]-[C:2]-[C:3].[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[C:3]-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]
null
[]
null
null
null
null
(2S,4R)-N-(4-Chloro-phenyl)-N-[1-(4-hydroxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide (207 mg, 0.481 mmol) was dissolved in DMF (5 mL) at room temperature. NaH (58 mg, 2.40 mmol) was added followed by 3-chloro-propane-1-sulfonic acid (sodium salt, 135 mg, 0.60 mmol) and the reaction was allowed to s...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HCl
CN(C)C=O
null
null
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.O=S(=O)(O)CCCCl>CN(C)C=O>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCS(=O)(=O)O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-fc90f4123de642d0ab9537c5d7803333
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(F)c(O)c2)c2ccccc21.COC(=O)C(C)(C)CCBr>>COC(=O)C(C)(C)CCOc1cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)ccc1F
ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC(=C(C=C1)F)O)=O)C.C(=O)([O-])[O-].[Cs+].[Cs+].BrCCC(C(=O)OC)(C)C>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C=1C=CC(=C(OCCC(C(=O)OC)(C)C)C1)F)C)C1=CC=C(C=C1)Cl
[OH:10][c:11]1[cH:12][c:13]([C:14](=[O:15])[N:16]2[c:17]3[cH:18][cH:19][cH:20][cH:21][c:22]3[C@H:23]([N:24]([C:25]([CH3:26])=[O:27])[c:28]3[cH:29][cH:30][c:31]([Cl:32])[cH:33][cH:34]3)[CH2:35][C@@H:36]2[CH3:37])[cH:38][cH:39][c:40]1[F:41].Br[CH2:9][CH2:8][C:5]([C:3]([O:2][CH3:1])=[O:4])([CH3:6])[CH3:7]>>[CH3:1][O:2][C:...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(F)c(O)c2)c2ccccc21.COC(=O)C(C)(C)CCBr
COC(=O)C(C)(C)CCOc1cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)ccc1F
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Br-[CH2;D2;+0:1]-[C:2]-[C:3]-[C:4](-[#8:5])=[O;D1;H0:6].[OH;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[#8:5]-[C:4](=[O;D1;H0:6])-[C:3]-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:7]-[c:8](:[c:9]):[c:10]
52
[{"value": 52.0, "product": "C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C=1C=CC(=C(OCCC(C(=O)OC)(C)C)C1)F)C)C1=CC=C(C=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 46.9, "product": "C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C=1C=CC(=C(OCCC(C(=O)OC)(C)C)C1)F)C)C1=CC=C(C=C1)Cl", "details": "CALC...
null
null
8
HOUR
N-(4-chlorophenyl)-N-[(2S,4R)-1-(4-fluoro-3-hydroxybenzoyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl]acetamide (476 mg, 1.05 mmol) was dissolved in DMF at room temperature and Cs2CO3 (854 mg, 2.63 mmol) was added. Methyl 4-bromo-2,2-dimethylbutanoate (702 mg, 1.58 mmol) was added and the reaction was stirred at r.t. ov...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HBr
CN(C)C=O
null
8
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(F)c(O)c2)c2ccccc21.COC(=O)C(C)(C)CCBr>CN(C)C=O>COC(=O)C(C)(C)CCOc1cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)ccc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5c62ccf86eb749f88ae578bd3cd8560d
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(F)c(O[Si](C)(C)C(C)(C)C)c2)c2ccccc21>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(F)c(O)c2)c2ccccc21
C(C)(C)(C)[Si](OC=1C=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=C(C=C2)Cl)C)C=CC1F)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC(=C(C=C1)F)O)=O)C
CC(C)(C)[Si](C)(C)[O:25][c:24]1[c:22]([F:23])[cH:21][cH:20][c:19]([C:17]([N:16]2[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]3[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]3)[c:32]3[c:27]2[cH:28][cH:29][cH:30][cH:31]3)=[O:18])[cH:26]1>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(F)c(O[Si](C)(C)C(C)(C)C)c2)c2ccccc21
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(F)c(O)c2)c2ccccc21
null
null
ClCCl
Deprotection
Alcohol deprotection from silyl ethers
e70131badc7d7d580ed75b2dfb3ce6df2a5f496b2119611cf5354e1267babe73
b09ece7bccc3ff762f4ff5407ad846fffba6d6a63735853c86a86d29904f54ed
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-C(-C)(-C)-[Si](-C)(-C)-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[OH;D1;+0:1]-[c:2](:[c:3]):[c:4]
110.9
[{"value": 100.0, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC(=C(C=C1)F)O)=O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 110.9, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC(=C(C=C1)F)O)=O)C", "details": "CALCULATEDPERCENTYIELD", "is_desired":...
null
null
null
null
N-[(2S,4R)-1-(3-{[tert-butyl-(dimethyl)silyl]oxy}-4-fluorobenzoyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl]-N-(4-chlorophenyl)acetamide (543 mg, 0.95 mmol) was dissolved in dichloromethane and a solution of TBAF (1.0 M in THF, 5.0 mL) was added; the reaction mixture was stirred at room temperature for until no startin...
10.6084/m9.figshare.5104873.v1
null
TMS ether protective group
Aromatic alcohol
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
Other
ClCCl
null
null
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(F)c(O[Si](C)(C)C(C)(C)C)c2)c2ccccc21>ClCCl>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(F)c(O)c2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4a9379993f7c4b638179dca48983574c
CCOC(=O)C1CCC(Oc2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc2)CC1>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OC3CCC(C(=O)O)CC3)cc2)c2ccccc21
C(C)OC(=O)C1CCC(CC1)OC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C.C(C)O.[OH-].[Na+]>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OC2CCC(CC2)C(=O)O)C=C1)C)C1=CC=C(C=C1)Cl
CC[O:30][C:28]([CH:27]1[CH2:26][CH2:25][CH:24]([O:23][c:22]2[cH:21][cH:20][c:19]([C:17]([N:16]3[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]4[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]4)[c:40]4[c:35]3[cH:36][cH:37][cH:38][cH:39]4)=[O:18])[cH:34][cH:33]2)[CH2:32][CH2:31]1)=[O:29]>>[CH3:1][C:2](=[O:3]...
CCOC(=O)C1CCC(Oc2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc2)CC1
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OC3CCC(C(=O)O)CC3)cc2)c2ccccc21
null
null
O1CCCC1
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(c1ccc(OC2CCCCC2)cc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
62
[{"value": 62.0, "product": "C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OC2CCC(CC2)C(=O)O)C=C1)C)C1=CC=C(C=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}]
null
null
10
HOUR
(2S,4R)-4-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-cyclohexanecarboxylic acid ethyl ester (0.060, 0.10 mmol) was hydrolyzed to the acid by dissolving in tetrahydrofuran and ethanol and sodium hydroxide (1N) was added. The mixture was stirred at room temperature 10 ho...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.c1ccccc1.C1CCCCC1.c1ccc2c(c1)CCC[NH]2
Other
O1CCCC1
null
10
CCOC(=O)C1CCC(Oc2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc2)CC1>O1CCCC1>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OC3CCC(C(=O)O)CC3)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-bb6a2808ad384237b06f54398dc5aa61
CC(=O)OCC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)c2ccccc21>>C[C@H]1C[C@@H](N(C(=O)CO)c2ccc(Cl)cc2)c2ccccc2N1
C(C)(=O)OCC(=O)N(C1=CC=C(C=C1)Cl)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)=O)C.[OH-].[K+].Cl>>ClC1=CC=C(C=C1)N(C(CO)=O)[C@@H]1C[C@@H](NC2=CC=CC=C12)C
CC(=O)[O:9][CH2:8][C:6]([N:5]([C@@H:4]1[CH2:3][C@H:2]([CH3:1])[N:23](C(=O)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)[c:22]2[c:17]1[cH:18][cH:19][cH:20][cH:21]2)[c:10]1[cH:11][cH:12][c:13]([Cl:14])[cH:15][cH:16]1)=[O:7]>>[CH3:1][C@H:2]1[CH2:3][C@@H:4]([N:5]([C:6](=[O:7])[CH2:8][OH:9])[c:10]2[cH:11][cH:12][c:13]([Cl:14])[cH:15][cH:16...
CC(=O)OCC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)c2ccccc21
C[C@H]1C[C@@H](N(C(=O)CO)c2ccc(Cl)cc2)c2ccccc2N1
null
null
O.C(C)O
Reduction
OtherReaction
cc3c05781d5bf0cc8d4d3d203997ba1665241eb99d100470add2c87f4a66cc78
83355dffd4f3f1a79824143fd500545d59e799dd65acc9de934ece20d30d5e94
c1ccc(N[C@@H]2CCNc3ccccc32)cc1
C-C(=O)-[O;H0;D2;+0:1]-[C:2]-[C:3](=[O;D1;H0:4])-[#7:5](-[c:6])-[C:7]1-[C:8]-[C:9](-[C;D1;H3:10])-[N;H0;D3;+0:11](-C(=O)-c2:c:c(-C(-F)(-F)-F):c:c(-C(-F)(-F)-F):c:2)-[c:12](:[c:13]):[c:14]-1>>[C;D1;H3:10]-[C:9]1-[C:8]-[C:7](-[#7:5](-[c:6])-[C:3](=[O;D1;H0:4])-[C:2]-[OH;D1;+0:1])-[c:14]:[c:12](:[c:13])-[NH;D2;+0:11]-1
null
[]
70
CELSIUS
null
null
To a solution of 2-[{(2S,4R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl}(4-chlorophenyl)amino]-2-oxoethyl acetate (500 mg, 0.82 mmol, 1 equ.) in ethanol (6 mL) and water (1 mL) was added potassium hydroxide (229 mg, 4.1 mmol, 5 equ.). The mixture was heated to 70° C. for 4 h. The mixtu...
10.6084/m9.figshare.5104873.v1
null
Trifluoro group.Trifluoro group.Ester.Tertiary amide
Primary alcohol.Secondary amine
c1ccccc1.c1ccc2c(c1)CCC[NH]2
c1ccc2c(c1)CCCN2
c1ccccc1.c1ccc2c(c1)CCCN2
HF
O.C(C)O
70
null
CC(=O)OCC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)c2ccccc21>O.C(C)O>C[C@H]1C[C@@H](N(C(=O)CO)c2ccc(Cl)cc2)c2ccccc2N1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-942d515f57e3447b811ce3444195e7b7
CC(=O)O.C[C@H]1C[C@@H](N(C(=O)CO)c2ccc(Cl)cc2)c2ccccc2N1>>CC(=O)OCC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)Nc2ccccc21
ClC1=CC=C(C=C1)N(C(CO)=O)[C@@H]1C[C@@H](NC2=CC=CC=C12)C.C(CCl)Cl.C(C)(=O)O>>C(C)(=O)OCC(=O)N([C@@H]1C[C@@H](NC2=CC=CC=C12)C)C1=CC=C(C=C1)Cl
O[C:2]([CH3:1])=[O:3].[OH:4][CH2:5][C:6](=[O:7])[N:8]([c:9]1[cH:10][cH:11][c:12]([Cl:13])[cH:14][cH:15]1)[C@@H:16]1[CH2:17][C@H:18]([CH3:19])[NH:20][c:21]2[cH:22][cH:23][cH:24][cH:25][c:26]21>>[CH3:1][C:2](=[O:3])[O:4][CH2:5][C:6](=[O:7])[N:8]([c:9]1[cH:10][cH:11][c:12]([Cl:13])[cH:14][cH:15]1)[C@@H:16]1[CH2:17][C@H:18...
CC(=O)O.C[C@H]1C[C@@H](N(C(=O)CO)c2ccc(Cl)cc2)c2ccccc2N1
CC(=O)OCC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)Nc2ccccc21
null
null
C(Cl)Cl
Acylation
Esterification of Carboxylic Acids
d9bd78214ee7dbc907e499722ae01849a72d188753963443e5df9fe42c31c43b
3652e761944e8ef7ee40675a156c8ae39909c72166786934d88652debf2ec1ac
c1ccc(N[C@@H]2CCNc3ccccc32)cc1
O-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[C:4]-[#7:5](-[c:6])-[C:7](=[O;D1;H0:8])-[C:9]-[OH;D1;+0:10]>>[C:4]-[#7:5](-[c:6])-[C:7](=[O;D1;H0:8])-[C:9]-[O;H0;D2;+0:10]-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3]
84
[{"value": 84.0, "product": "C(C)(=O)OCC(=O)N([C@@H]1C[C@@H](NC2=CC=CC=C12)C)C1=CC=C(C=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 70.7, "product": "C(C)(=O)OCC(=O)N([C@@H]1C[C@@H](NC2=CC=CC=C12)C)C1=CC=C(C=C1)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
20
HOUR
N-(4-Chlorophenyl)-2-hydroxy-N-[(2S,4R)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl]acetamide (300 mg, 0.91 mmol, 1 equ.) was dissolved in methylene chloride (3 mL). To this solution was added EDC (464 mg, 2.7 mmol, 3 equ.) and acetic acid (164 mg, 2.7 mmol, 3 equ.) and the reaction mixture was stirred at room temperature...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary alcohol
Ester
null
null
c1ccccc1.c1ccc2c(c1)CCCN2
HO-
C(Cl)Cl
null
20
CC(=O)O.C[C@H]1C[C@@H](N(C(=O)CO)c2ccc(Cl)cc2)c2ccccc2N1>C(Cl)Cl>CC(=O)OCC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)Nc2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d66277e98d1f4a59a5cad9023b6c3b9e
CC(=O)OCC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)Nc2ccccc21.COC(=O)C(C)(C)CCCc1ccc(C(=O)Cl)cc1>>COC(=O)C(C)(C)CCCc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)COC(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
ClC(=O)C1=CC=C(C=C1)CCCC(C(=O)OC)(C)C.C(C)(=O)OCC(=O)N([C@@H]1C[C@@H](NC2=CC=CC=C12)C)C1=CC=C(C=C1)Cl.C(C)(C)N(CC)C(C)C>>C(C)(=O)OCC(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)CCCC(C(=O)OC)(C)C)C)C1=CC=C(C=C1)Cl
[NH:17]1[c:18]2[cH:19][cH:20][cH:21][cH:22][c:23]2[C@H:24]([N:25]([C:26](=[O:27])[CH2:28][O:29][C:30]([CH3:31])=[O:32])[c:33]2[cH:34][cH:35][c:36]([Cl:37])[cH:38][cH:39]2)[CH2:40][C@@H:41]1[CH3:42].Cl[C:15]([c:14]1[cH:13][cH:12][c:11]([CH2:10][CH2:9][CH2:8][C:5]([C:3]([O:2][CH3:1])=[O:4])([CH3:6])[CH3:7])[cH:44][cH:43]...
CC(=O)OCC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)Nc2ccccc21.COC(=O)C(C)(C)CCCc1ccc(C(=O)Cl)cc1
COC(=O)C(C)(C)CCCc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)COC(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
null
null
C(Cl)Cl
Acylation
N-alkylation of secondary amines with alkyl halides
20af49e2ebd8e13ce8273786fd70e980d9c80eb9362be37fe2fe9cf2d75c9b8d
96cb0a2fed10552c5770a45a2d6523b47ac3e38928b4a9c698d8577451182dcd
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C:6]-[C:7](-[C;D1;H3:8])-[NH;D2;+0:9]-[c:10](:[c:11]):[c:12]>>[C:6]-[C:7](-[C;D1;H3:8])-[N;H0;D3;+0:9](-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5])-[c:10](:[c:11]):[c:12]
40
[{"value": 40.0, "product": "C(C)(=O)OCC(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)CCCC(C(=O)OC)(C)C)C)C1=CC=C(C=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 39.5, "product": "C(C)(=O)OCC(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)CCCC(C(=O)OC)(C)C)C)C1=CC=C(C=C1)Cl", "details...
null
null
null
null
To a solution of 2-{(4-chlorophenyl)[(2S,4R)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl]amino}-2-oxoethyl acetate (170 mg, 0.45 mmol, 1 equ.) in methylene chloride (2.0 mL) at room temperature was added diisopropylethylamine (127 uL, 0.73 mmol, 1.60 equ.) followed by methyl 5-[4-(chlorocarbonyl)phenyl]-2,2-dimethylpentan...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Secondary amine
Tertiary amide
c1ccc2c(c1)CCCN2
c1ccc2c(c1)CCC[NH]2
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HCl
C(Cl)Cl
null
null
CC(=O)OCC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)Nc2ccccc21.COC(=O)C(C)(C)CCCc1ccc(C(=O)Cl)cc1>C(Cl)Cl>COC(=O)C(C)(C)CCCc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)COC(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-6194b864aa8a4b1e9ac5f444369a9624
CN1CC(O)CC1C(=O)O.C[Si](C)(C)C=[N+]=[N-]>>COC(=O)C1CC(O)CN1C
OC1CC(N(C1)C)C(=O)O.C[Si](C)(C)C=[N+]=[N-]>>COC(=O)C1N(CC(C1)O)C
[OH:2][C:3](=[O:4])[CH:5]1[CH2:6][CH:7]([OH:8])[CH2:9][N:10]1[CH3:11].C[Si](C)(C)[CH:1]=[N+]=[N-]>>[CH3:1][O:2][C:3](=[O:4])[CH:5]1[CH2:6][CH:7]([OH:8])[CH2:9][N:10]1[CH3:11]
CN1CC(O)CC1C(=O)O.C[Si](C)(C)C=[N+]=[N-]
COC(=O)C1CC(O)CN1C
null
null
CO
Heteroatom Alkylation and Arylation
O-alkylation of carboxylic acids with diazo compounds
39589be0e9a30df66714fe618d22a8ac0fb24901dbf2ead1ab33e31556c7ac64
8b539baf7aeb5ab868833e33306bad77200a853d562904197e13de2e27e229d7
C1CCNC1
C-[Si](-C)(-C)-[CH;D2;+0:1]=[N+]=[N-].[#7:2]-[C:3]-[C:4](=[O;D1;H0:5])-[OH;D1;+0:6]>>[#7:2]-[C:3]-[C:4](=[O;D1;H0:5])-[O;H0;D2;+0:6]-[CH3;D1;+0:1]
null
[]
null
null
null
null
4-Hydroxy-1-methyl-pyrrolidine-2-carboxylic acid (0.27 g, 1.85 mmol) was dissolved in 5 ml methanol at room temperature and (trimethylsilyl)diazomethane (2M solution in hexane) was added until solution become yellow. The mixture was concentrated down to afford crude 4-hydroxy-1-methyl-pyrrolidine-2-carboxylic acid meth...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Diazo.Silyl protective group
Ester
null
null
C1CC[NH]C1
Other
CO
null
null
CN1CC(O)CC1C(=O)O.C[Si](C)(C)C=[N+]=[N-]>CO>COC(=O)C1CC(O)CN1C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-57d4663b805f49958326765e43d5b9ad
BrCCCc1cccnc1.CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCc3cccnc3)cc2)c2ccccc21
ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)O)=O)C.C(=O)([O-])[O-].[K+].[K+].BrCCCC=1C=NC=CC1>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCCCC=1C=NC=CC1)=O)C
Br[CH2:24][CH2:25][CH2:26][c:27]1[cH:28][cH:29][cH:30][n:31][cH:32]1.[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]([OH:23])[cH:33][cH:34]2)[c:35]2[cH:36][cH:37][cH:38][cH:39][c:40]21>>[CH3:1][C:2](=[O:3])[N:...
BrCCCc1cccnc1.CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCc3cccnc3)cc2)c2ccccc21
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
O=C(c1ccc(OCCCc2cccnc2)cc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Br-[CH2;D2;+0:1]-[C:2]-[C:3].[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[C:3]-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]
null
[]
90
CELSIUS
null
null
(2S,4R)-N-(4-Chloro-phenyl)-N-[1-(4-hydroxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide was dissolved in DMF (5 mL) at room temperature. K2CO3 was added followed by 3-(3-bromo-propyl)-pyridine and the reaction was allowed to stir at 90° C. over night. The reaction mixture was concentrated in vacuo. Th...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccccc1.c1ccncc1.c1ccc2c(c1)CCC[NH]2
HBr
CN(C)C=O
90
null
BrCCCc1cccnc1.CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21>CN(C)C=O>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCc3cccnc3)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-0975063f50214ea4ad66ecdb8ca58fe1
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCc3ccc(C(=O)O)o3)cc2)c2ccccc21.[NH4+]>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCc3ccc(C(N)=O)o3)cc2)c2ccccc21
C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCC2=CC=C(O2)C(=O)O)C=C1)C)C1=CC=C(C=C1)Cl.C=1C=CC2=C(C1)N=NN2O.CCN=C=NCCCN(C)C.[Cl-].[NH4+]>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCC2=CC=C(O2)C(=O)N)C=C1)C)C1=CC=C(C=C1)Cl
O[C:29]([c:28]1[cH:27][cH:26][c:25]([CH2:24][O:23][c:22]2[cH:21][cH:20][c:19]([C:17]([N:16]3[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]4[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]4)[c:40]4[c:35]3[cH:36][cH:37][cH:38][cH:39]4)=[O:18])[cH:34][cH:33]2)[o:32]1)=[O:31].[NH4+:30]>>[CH3:1][C:2](=[O:3])[N...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCc3ccc(C(=O)O)o3)cc2)c2ccccc21.[NH4+]
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCc3ccc(C(N)=O)o3)cc2)c2ccccc21
null
CN(C)C=O
C(C)(=O)OCC.C1CCOC1
Acylation
Carboxylic acid to amide conversion
1283aef55d7ee699f097a8e5267689198c76ba671644401547f902657820236d
cb0a71c3fb37a76e96fbd81aae6f95a28398a03d1ad2c8e877085e735efb98f1
O=C(c1ccc(OCc2ccco2)cc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#8;a:5]:[c:6].[NH4+;D0:7]>>[NH2;D1;+0:7]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#8;a:5]:[c:6]
61
[{"value": 61.0, "product": "C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCC2=CC=C(O2)C(=O)N)C=C1)C)C1=CC=C(C=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}]
null
null
11
HOUR
(2S,4R)-5-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxymethyl)-furan-2-carboxylic acid (0.065 g, 0.12 mmol) was converted to the amide by dissolving in THF (1 mL) at room temperature. HOBt (0.024 g), EDCI (0.033 g), and ammonium chloride (0.013 g, 0.232 mmol) was added alo...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
Primary amide
null
null
c1ccccc1.c1ccccc1.c1ccoc1.c1ccc2c(c1)CCC[NH]2
HO-
CN(C)C=O.C(C)(=O)OCC.C1CCOC1
null
11
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCc3ccc(C(=O)O)o3)cc2)c2ccccc21.[NH4+]>CN(C)C=O.C(C)(=O)OCC.C1CCOC1>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCc3ccc(C(N)=O)o3)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f453b0676496406c9cd3738e011c6da1
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN3CCN(C(=O)OC(C)(C)C)CC3)cc2)c2ccccc21.CC(C)(C)OC(=O)N1CCN(CCCCl)CC1>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN3CCNCC3)cc2)c2ccccc21
C(=O)([O-])[O-].[K+].[K+].C(C)(C)(C)OC(=O)N1CCN(CC1)CCCOC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C.ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)O)=O)C.C(C)(C)(C)OC(=O)N1CCN(CC1)CCCCl>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCCCN1CCNCC1)...
[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]([OH:23])[cH:33][cH:34]2)[c:35]2[cH:36][cH:37][cH:38][cH:39][c:40]21.CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O[CH2:24][CH2:25][CH2:26]N3CCN(C(=O)OC(C)(C...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN3CCN(C(=O)OC(C)(C)C)CC3)cc2)c2ccccc21.CC(C)(C)OC(=O)N1CCN(CCCCl)CC1
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN3CCNCC3)cc2)c2ccccc21
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
2e90dc5a2a34d7606cb364a22871edc1bf43aab8a1b98625588a8e5ad1b9e0c6
bfa789cac20a4cd0c25eaf6f43e2b2ee089209e3d34aa8afab8b6fd61ef4b300
O=C(c1ccc(OCCCN2CCNCC2)cc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1]1-[C:2]-[C:3]-[N;H0;D3;+0:4](-C-C-C-Cl)-[C:5]-[C:6]-1.C-C(=O)-N(-[C@H]1-C-[C@H](-C)-N(-C(=O)-c2:c:c:c(-O-[CH2;D2;+0:7]-[C:8]-[CH2;D2;+0:9]-N3-C-C-N(-C(=O)-O-C(-C)(-C)-C)-C-C-3):c:c:2)-c2:c:c:c:c:c:2-1)-c1:c:c:c(-Cl):c:c:1.[OH;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[c:12]:[c:11](-[O;H0;D2;+0...
50
[{"value": 50.0, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCCCN1CCNCC1)=O)C", "details": "PERCENTYIELD", "is_desired": false}]
80
CELSIUS
null
null
(2S,4R)-N-(4-Chloro-phenyl)-N-{2-methyl-1-[4-(3-piperazin-1-yl-propoxy)-benzoyl]-1,2,3,4-tetrahydro-quinolin-4-yl}-acetamide was prepared from (2S,4R)-4-[3-(4-{4-[acetyl(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-propyl]-piperazine-1-carboxylic acid tert-butyl ester. (2S,4R)-N-(4-Chl...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary halide.Carbamic ester.Carbamic ester.Ether.Ether.Ether.Tertiary amide.Tertiary amide.Aromatic alcohol.Tertiary amine.Tertiary amine.Boc.Boc
Ether.Secondary amine.Tertiary amine
c1ccccc1.c1ccccc1.C1CNCCN1.c1ccc2c(c1)CCCN2.C1C[NH]CC[NH]1
C1C[NH]CCN1
c1ccccc1.c1ccccc1.C1C[NH]CCN1.c1ccc2c(c1)CCC[NH]2
HCl
CN(C)C=O
80
null
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN3CCN(C(=O)OC(C)(C)C)CC3)cc2)c2ccccc21.CC(C)(C)OC(=O)N1CCN(CCCCl)CC1>CN(C)C=O>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN3CCNCC3)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7700194ea30e4e7da9ed7288a7c2fb68
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN3CCN(C(=O)OC(C)(C)C)CC3)cc2)c2ccccc21>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN3CCNCC3)cc2)c2ccccc21
C(C)(C)(C)OC(=O)N1CCN(CC1)CCCOC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCCCN1CCNCC1)=O)C
CC(C)(C)OC(=O)[N:30]1[CH2:29][CH2:28][N:27]([CH2:26][CH2:25][CH2:24][O:23][c:22]2[cH:21][cH:20][c:19]([C:17]([N:16]3[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]4[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]4)[c:40]4[c:35]3[cH:36][cH:37][cH:38][cH:39]4)=[O:18])[cH:34][cH:33]2)[CH2:32][CH2:31]1>>[CH3:1...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN3CCN(C(=O)OC(C)(C)C)CC3)cc2)c2ccccc21
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN3CCNCC3)cc2)c2ccccc21
null
null
Cl.O1CCOCC1
Reduction
Boc amine deprotection
2c25e19aee181a3c5131cfdfda27035fd54d4379a11d745dfb75d386bacfd500
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
O=C(c1ccc(OCCCN2CCNCC2)cc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1>>[#7:4]1-[C:3]-[C:2]-[NH;D2;+0:1]-[C:6]-[C:5]-1
100
[{"value": 100.0, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCCCN1CCNCC1)=O)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
(2S,4R)-N-(4-Chloro-phenyl)-N-{2-methyl-1-[4-(3-piperazin-1-yl-propoxy)-benzoyl]-1,2,3,4-tetrahydro-quinolin-4-yl}-acetamide was prepared from (2S,4R)-4-[3-(4-{4-[acetyl(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-propyl]-piperazine-1-carboxylic acid tert-butyl ester. (2S,4R)-N-(4-Chl...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
C1C[NH]CC[NH]1
C1C[NH]CCN1
c1ccccc1.c1ccccc1.C1C[NH]CCN1.c1ccc2c(c1)CCC[NH]2
HO-
Cl.O1CCOCC1
null
2
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN3CCN(C(=O)OC(C)(C)C)CC3)cc2)c2ccccc21>Cl.O1CCOCC1>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN3CCNCC3)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3061ed6efacc4b96a7b16685ded4c08a
COc1c(F)cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1F>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc(F)c(O)c(F)c2)c2ccccc21
ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC(=C(C(=C1)F)OC)F)=O)C.B(Br)(Br)Br>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC(=C(C(=C1)F)O)F)=O)C
C[O:24][c:23]1[c:21]([F:22])[cH:20][c:19]([C:17]([N:16]2[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]3[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]3)[c:33]3[c:28]2[cH:29][cH:30][cH:31][cH:32]3)=[O:18])[cH:27][c:25]1[F:26]>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:...
COc1c(F)cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1F
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc(F)c(O)c(F)c2)c2ccccc21
null
null
ClCCl
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[OH;D1;+0:1]-[c:2](:[c:3]):[c:4]
78.7
[{"value": 78.0, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC(=C(C(=C1)F)O)F)=O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 78.7, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC(=C(C(=C1)F)O)F)=O)C", "details": "CALCULATEDPERCENTYIELD", "is_desir...
null
null
null
null
N-(4-chlorophenyl)-N-[(2S,4R)-1-(3,5-difluoro-4-methoxybenzoyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl]acetamide (200 mg, 0.41 mmol) was dissolved in dichloromethane and a solution of BBr3 (1.0 M in dichloromethane, 10 mL) was added; the reaction was allowed to stir at room temperature for until no starting material ...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
Other
ClCCl
null
null
COc1c(F)cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1F>ClCCl>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc(F)c(O)c(F)c2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-89a3a2907acd4c60942e8903b4fca9a9
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc(F)c(O)c(F)c2)c2ccccc21.COC(=O)C(C)(C)CCBr>>COC(=O)C(C)(C)CCOc1c(F)cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1F
ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC(=C(C(=C1)F)O)F)=O)C.C(=O)([O-])[O-].[Cs+].[Cs+].BrCCC(C(=O)OC)(C)C>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC(=C(OCCC(C(=O)OC)(C)C)C(=C1)F)F)C)C1=CC=C(C=C1)Cl
[OH:10][c:11]1[c:12]([F:13])[cH:14][c:15]([C:16](=[O:17])[N:18]2[c:19]3[cH:20][cH:21][cH:22][cH:23][c:24]3[C@H:25]([N:26]([C:27]([CH3:28])=[O:29])[c:30]3[cH:31][cH:32][c:33]([Cl:34])[cH:35][cH:36]3)[CH2:37][C@@H:38]2[CH3:39])[cH:40][c:41]1[F:42].Br[CH2:9][CH2:8][C:5]([C:3]([O:2][CH3:1])=[O:4])([CH3:6])[CH3:7]>>[CH3:1][...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc(F)c(O)c(F)c2)c2ccccc21.COC(=O)C(C)(C)CCBr
COC(=O)C(C)(C)CCOc1c(F)cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1F
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Br-[CH2;D2;+0:1]-[C:2]-[C:3]-[C:4](-[#8:5])=[O;D1;H0:6].[OH;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[#8:5]-[C:4](=[O;D1;H0:6])-[C:3]-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:7]-[c:8](:[c:9]):[c:10]
61.6
[{"value": 61.0, "product": "C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC(=C(OCCC(C(=O)OC)(C)C)C(=C1)F)F)C)C1=CC=C(C=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 61.6, "product": "C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC(=C(OCCC(C(=O)OC)(C)C)C(=C1)F)F)C)C1=CC=C(C=C1)Cl", "details":...
null
null
8
HOUR
N-(4-chlorophenyl)-N-[(2S,4R)-1-(3,5-difluoro-4-hydroxybenzoyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl]acetamide (150 mg, 0.32 mmol) was dissolved in DMF at room temperature and Cs2CO3 (259 mg, 0.80 mmol) was added. Methyl 4-bromo-2,2-dimethylbutanoate (157 mg, 0.48 mmol) was added and the reaction was stirred at roo...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HBr
CN(C)C=O
null
8
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc(F)c(O)c(F)c2)c2ccccc21.COC(=O)C(C)(C)CCBr>CN(C)C=O>COC(=O)C(C)(C)CCOc1c(F)cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-febfa0afe65845b4a5376e0a5e2deaa6
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N3CCC(C(=O)O)CC3)cc2)c2ccccc21.[NH4+]>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N3CCC(C(N)=O)CC3)cc2)c2ccccc21
[Cl-].[NH4+].C=1C=CC2=C(C1)N=NN2O.CN(C)C(=[N+](C)C)ON1C2=C(C=CC=N2)N=N1.F[P-](F)(F)(F)(F)F.C(C)(C)N(CC)C(C)C.C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)N1CCC(CC1)C(=O)O)C)C1=CC=C(C=C1)Cl>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)N1CCC(CC1)C(=O)N)C)C1=CC=C(C=C1)Cl
O[C:27]([CH:26]1[CH2:25][CH2:24][N:23]([c:22]2[cH:21][cH:20][c:19]([C:17]([N:16]3[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]4[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]4)[c:39]4[c:34]3[cH:35][cH:36][cH:37][cH:38]4)=[O:18])[cH:33][cH:32]2)[CH2:31][CH2:30]1)=[O:29].[NH4+:28]>>[CH3:1][C:2](=[O:3])[N:...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N3CCC(C(=O)O)CC3)cc2)c2ccccc21.[NH4+]
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N3CCC(C(N)=O)CC3)cc2)c2ccccc21
null
null
CN(C)C=O.C(C)(=O)OCC
Acylation
Carboxylic acid to amide conversion
1283aef55d7ee699f097a8e5267689198c76ba671644401547f902657820236d
cb0a71c3fb37a76e96fbd81aae6f95a28398a03d1ad2c8e877085e735efb98f1
O=C(c1ccc(N2CCCCC2)cc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])-[C:5].[NH4+;D0:6]>>[C:4]-[C:3](-[C;H0;D3;+0:1](-[NH2;D1;+0:6])=[O;D1;H0:2])-[C:5]
null
[]
null
null
16
HOUR
(2S,4R)-1-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenyl)-piperidine-4-carboxylic acid amide was prepared from (2S,4R)-1-(4-{4-[acetyl(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenyl)-piperidine-4-carboxylic acid. The acid (0.120 g, 0.22 mmol) wa...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
Primary amide
null
null
c1ccccc1.c1ccccc1.C1CC[NH]CC1.c1ccc2c(c1)CCC[NH]2
HO-
CN(C)C=O.C(C)(=O)OCC
null
16
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N3CCC(C(=O)O)CC3)cc2)c2ccccc21.[NH4+]>CN(C)C=O.C(C)(=O)OCC>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N3CCC(C(N)=O)CC3)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8ebfd296bffc4168bc484359eb1ddf50
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)nc2)c2ccccc21.COC(=O)C(C)(C)CCBr.COC(=O)C(C)(C)CCBr.COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cn1>>COC(=O)C(C)(C)CCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cn1.COC(=O)C(C)(C)CCn1cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H...
ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C=1C=NC(=CC1)OC)C.ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C=1C=NC(=CC1)OC)C.[Si](C)(C)(C)I.BrCCC(C(=O)OC)(C)C.[Al].ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C=1C=NC(=CC1)O)C.BrCCC(C(=O)OC)(C)C>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=C...
[OH:10][c:11]1[cH:12][cH:13][c:14]([C:15](=[O:16])[N:17]2[c:18]3[cH:19][cH:20][cH:21][cH:22][c:23]3[C@H:24]([N:25]([C:26]([CH3:27])=[O:28])[c:29]3[cH:30][cH:31][c:32]([Cl:33])[cH:34][cH:35]3)[CH2:36][C@@H:37]2[CH3:38])[cH:39][n:40]1.Br[CH2:49][CH2:48][C:45]([C:43]([O:42][CH3:41])=[O:44])([CH3:46])[CH3:47].Br[CH2:9][CH2...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)nc2)c2ccccc21.COC(=O)C(C)(C)CCBr.COC(=O)C(C)(C)CCBr.COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cn1
COC(=O)C(C)(C)CCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cn1.COC(=O)C(C)(C)CCn1cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)ccc1=O
null
C([O-])([O-])=O.[Ag+2]
CN(C=O)C.C(Cl)Cl
Acylation
OtherReaction
cb3eea33e8070e9f3f5e11706ed3969c0f32e648b1ff89d9d81d8c48963d0925
eed310011e237c9d1634b8d2011b7ae3f1598bae2c40f6e7c8627702087e358a
O=C(c1ccc(=O)[nH]c1)N1CC[C@@H](Nc2ccccc2)c2ccccc21.O=C(c1cccnc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Br-[CH2;D2;+0:1]-[C:2]-[C:3]-[C:4](-[#8:5])=[O;D1;H0:6].Br-[CH2;D2;+0:7]-[C:8]-[C:9]-[C:10](-[#8:11])=[O;D1;H0:12].C-[O;H0;D2;+0:13]-[c;H0;D3;+0:14]1:[c:15]:[c:16]:[c:17](-[C:18](-[#7:19])=[O;D1;H0:20]):[c:21]:[n;H0;D2;+0:22]:1.[OH;D1;+0:23]-[c:24](:[c:25]):[#7;a:26]:[c:27]>>[#7:19]-[C:18](=[O;D1;H0:20])-[c:17]1:[c:21]...
32
[{"value": 32.0, "product": "C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C=1C=CC(=NC1)OCCC(C(=O)OC)(C)C)C)C1=CC=C(C=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 32.0, "product": "C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C=1C=CC(N(C1)CCC(C(=O)OC)(C)C)=O)C)C1=CC=C(C=C1)Cl", "details": "PERCENTY...
null
null
14
HOUR
Methyl 4-[(5-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}pyridin-2-yl)oxy]-2,2-dimethylbutanoate was prepared from (2S,4R)-N-(4-chloro-phenyl)-N-[1-(6-methoxy-pyridine-3-carbonyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide by deprotection of the methoxy and elabora...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Primary halide.Ether.Aromatic alcohol
Ether
c1ccncc1
c1ccncc1
c1ccncc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2.c1ccncc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HBr
C([O-])([O-])=O.[Ag+2].CN(C=O)C.C(Cl)Cl
null
14
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)nc2)c2ccccc21.COC(=O)C(C)(C)CCBr.COC(=O)C(C)(C)CCBr.COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cn1>C([O-])([O-])=O.[Ag+2].CN(C=O)C.C(Cl)Cl>COC(=O)C(C)(C)CCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cn1.COC(=O)C(C)(C)CCn1cc(C(=O)N2c3c...
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4427dbe6f55d4b5a9b94c15c61ee6b54
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(CN)cc2)c2ccccc21>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(C#N)cc2)c2ccccc21
NCC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=C(C=C2)Cl)C)C=C1.FC(C1=NC=C(CCl)C=C1)(F)F>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)C#N)=O)C
[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]([CH2:23][NH2:24])[cH:25][cH:26]2)[c:27]2[cH:28][cH:29][cH:30][cH:31][c:32]21>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(CN)cc2)c2ccccc21
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(C#N)cc2)c2ccccc21
null
null
null
Oxidation
OtherReaction
ac5c3ce1830d1d2f361a1aa656654ba2cf9d12f5ae14f5bbc507e5ce2e782a9d
6be52931fddcbf34eb2e47e72b291d97a0f52d81412705e5a3068ffcb8150fea
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
[NH2;D1;+0:1]-[CH2;D2;+0:2]-[c:3](:[c:4]):[c:5]>>[N;H0;D1;+0:1]#[C;H0;D2;+0:2]-[c:3](:[c:4]):[c:5]
null
[]
null
null
null
null
N-{(2S,4R)-1-[4-(aminomethyl)benzoyl]-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl}-N-(4-chlorophenyl)acetamide was made following general procedure H, substituting 4-cyanobenzoyl chloride for 6-trifluoromethyl nicotinyl chloride. The rest of the procedure is followed as indicated in general procedure H to yield the corres...
10.6084/m9.figshare.5104873.v1
null
Primary amine
Nitrile
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
null
null
null
null
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(CN)cc2)c2ccccc21>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(C#N)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-93c98320a7f3439db997db72a95d930e
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(C#N)cc2)c2ccccc21>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(CN)cc2)c2ccccc21
[BH4-].[Na+].ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)C#N)=O)C>>NCC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=C(C=C2)Cl)C)C=C1
[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]([C:23]#[N:24])[cH:25][cH:26]2)[c:27]2[cH:28][cH:29][cH:30][cH:31][c:32]21>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(C#N)cc2)c2ccccc21
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(CN)cc2)c2ccccc21
null
[Co](Cl)Cl
C(C)O
Reduction
Reduction of nitrile to amine
65bec2d9f430701d30dc9fcbe1c5418f3dfa174d67be035c50edfc71895dc9c7
e8d1bc928b94bd4f5bf4b23363ce8f88b1ce7d146ba93829e7b8ad8dbe0007a7
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
[N;H0;D1;+0:1]#[C;H0;D2;+0:2]-[c:3](:[c:4]):[c:5]>>[NH2;D1;+0:1]-[CH2;D2;+0:2]-[c:3](:[c:4]):[c:5]
83
[{"value": 83.0, "product": "NCC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=C(C=C2)Cl)C)C=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 82.3, "product": "NCC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=C(C=C2)Cl)C)C=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
N-{(2S,4R)-1-[4-(aminomethyl)benzoyl]-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl}-N-(4-chlorophenyl)acetamide was made following general procedure H, substituting 4-cyanobenzoyl chloride for 6-trifluoromethyl nicotinyl chloride. The rest of the procedure is followed as indicated in general procedure H to yield the corres...
10.6084/m9.figshare.5104873.v1
null
Nitrile
Primary amine
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
null
[Co](Cl)Cl.C(C)O
null
2
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(C#N)cc2)c2ccccc21>[Co](Cl)Cl.C(C)O>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(CN)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b720726e9c70432e8a451e15e34acb90
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1F>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)c(F)c2)c2ccccc21
ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC(=C(C=C1)OC)F)=O)C.B(Br)(Br)Br>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC(=C(C=C1)O)F)=O)C
C[O:23][c:22]1[cH:21][cH:20][c:19]([C:17]([N:16]2[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]3[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]3)[c:32]3[c:27]2[cH:28][cH:29][cH:30][cH:31]3)=[O:18])[cH:26][c:24]1[F:25]>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH...
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1F
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)c(F)c2)c2ccccc21
null
null
ClCCl
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[OH;D1;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
null
null
null
null
N-(4-chlorophenyl)-N-[(2S,4R)-1-(3-fluoro-4-methoxybenzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]acetamide was dissolved in dichloromethane and a solution of BBr3 (1.0 M in dichloromethane, 10 mL) was added; the reaction was allowed to stir at room temperature for until no starting material remained. The reaction ...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
Other
ClCCl
null
null
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1F>ClCCl>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)c(F)c2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-67ed045c76d94923a3d9d06a441c196a
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)c(F)c2)c2ccccc21.COC(=O)C(C)(C)CCBr>>COC(=O)C(C)(C)CCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1F
ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC(=C(C=C1)O)F)=O)C.C(=O)([O-])[O-].[Cs+].[Cs+].BrCCC(C(=O)OC)(C)C>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC(=C(OCCC(C(=O)OC)(C)C)C=C1)F)C)C1=CC=C(C=C1)Cl
[OH:10][c:11]1[cH:12][cH:13][c:14]([C:15](=[O:16])[N:17]2[c:18]3[cH:19][cH:20][cH:21][cH:22][c:23]3[C@H:24]([N:25]([C:26]([CH3:27])=[O:28])[c:29]3[cH:30][cH:31][c:32]([Cl:33])[cH:34][cH:35]3)[CH2:36][C@@H:37]2[CH3:38])[cH:39][c:40]1[F:41].Br[CH2:9][CH2:8][C:5]([C:3]([O:2][CH3:1])=[O:4])([CH3:6])[CH3:7]>>[CH3:1][O:2][C:...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)c(F)c2)c2ccccc21.COC(=O)C(C)(C)CCBr
COC(=O)C(C)(C)CCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1F
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Br-[CH2;D2;+0:1]-[C:2]-[C:3]-[C:4](-[#8:5])=[O;D1;H0:6].[OH;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[#8:5]-[C:4](=[O;D1;H0:6])-[C:3]-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:7]-[c:8](:[c:9]):[c:10]
43.3
[{"value": 43.0, "product": "C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC(=C(OCCC(C(=O)OC)(C)C)C=C1)F)C)C1=CC=C(C=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 43.3, "product": "C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC(=C(OCCC(C(=O)OC)(C)C)C=C1)F)C)C1=CC=C(C=C1)Cl", "details": "CALC...
null
null
8
HOUR
N-(4-chlorophenyl)-N-[(2S,4R)-1-(3-fluoro-4-hydroxybenzoyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl]acetamide (317 mg, 0.70 mmol) was dissolved in DMF at room temperature and Cs2CO3 (567 mg, 1.75 mmol) was added. Methyl 4-bromo-2,2-dimethylbutanoate (465 mg, 1.05 mmol) was added and the reaction was stirred at room te...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HBr
CN(C)C=O
null
8
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)c(F)c2)c2ccccc21.COC(=O)C(C)(C)CCBr>CN(C)C=O>COC(=O)C(C)(C)CCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c5298b408298432e9b34470546c398e6
CC(=O)N(c1ccc(Cl)cc1)C1CC(C)N(C(=O)c2ccc(N)cc2)c2ccccc21.O=C=NCCCl>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N3CCNC3=O)cc2)c2ccccc21
NC1=CC=C(C(=O)N2C(CC(C3=CC=CC=C23)N(C(C)=O)C2=CC=C(C=C2)Cl)C)C=C1.C(C)N(CC)CC.ClCCN=C=O>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)N1C(NCC1)=O)=O)C
[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[CH:12]1[CH2:13][CH:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]([NH2:23])[cH:29][cH:30]2)[c:31]2[cH:32][cH:33][cH:34][cH:35][c:36]21.Cl[CH2:24][CH2:25][N:26]=[C:27]=[O:28]>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9...
CC(=O)N(c1ccc(Cl)cc1)C1CC(C)N(C(=O)c2ccc(N)cc2)c2ccccc21.O=C=NCCCl
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N3CCNC3=O)cc2)c2ccccc21
null
null
C(Cl)Cl
Acylation
OtherReaction
f37cf7a9ad0f5f76d1e1865cfd1e56f59ddf36de00b20b3db75c778c41365215
4027078f43f05c269e15aab569503cb296a7859c76790295b091602f9a2be99b
O=C1NCCN1c1ccc(C(=O)N2CC[C@@H](Nc3ccccc3)c3ccccc32)cc1
Cl-[CH2;D2;+0:1]-[C:2]-[N;H0;D2;+0:3]=[C;H0;D2;+0:4]=[O;D1;H0:5].[NH2;D1;+0:6]-[c:7](:[c:8]):[c:9]>>[O;D1;H0:5]=[C;H0;D3;+0:4]1-[NH;D2;+0:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:6]-1-[c:7](:[c:8]):[c:9]
null
[]
null
null
null
null
N-[1-(4-Amino-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-N-(4-chloro-phenyl)-acetamide (156 mg, 0.373 mmol) was dissolved in methylene chloride (3 mL) and was added triethylamine (0.078 mL, 0.559 mmol) and 1-chloro-2-isocyanato-ethane 0.038 mL, 0.448 mmol). The reaction was stirred at room temperature over nig...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Isocyanate.Primary amine
Urea
null
C1CNC[NH]1
c1ccccc1.c1ccccc1.C1CNC[NH]1.c1ccc2c(c1)CCC[NH]2
HCl
C(Cl)Cl
null
null
CC(=O)N(c1ccc(Cl)cc1)C1CC(C)N(C(=O)c2ccc(N)cc2)c2ccccc21.O=C=NCCCl>C(Cl)Cl>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N3CCNC3=O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-016c0a28ebad401fb22e451500a15c10
COC(=O)CCCN(C)c1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N(C)CCCC(=O)O)cc2)c2ccccc21
C(C)O.[OH-].[Li+].COC(CCCN(C)C1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C)=O>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)N(CCCC(=O)O)C)C)C1=CC=C(C=C1)Cl
C[O:30][C:28]([CH2:27][CH2:26][CH2:25][N:23]([c:22]1[cH:21][cH:20][c:19]([C:17]([N:16]2[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]3[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]3)[c:38]3[c:33]2[cH:34][cH:35][cH:36][cH:37]3)=[O:18])[cH:32][cH:31]1)[CH3:24])=[O:29]>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:...
COC(=O)CCCN(C)c1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N(C)CCCC(=O)O)cc2)c2ccccc21
null
null
O1CCCC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
null
[]
50
CELSIUS
null
null
(2S,4R)-4-[(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenyl)-methyl-amino]-butyric acid was prepared from (2S,4R)-4-[(4-{4-[acetyl(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenyl)-methyl-amino]-butyric acid methyl ester was hydrolyzed to the acid b...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
Other
O1CCCC1
50
null
COC(=O)CCCN(C)c1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1>O1CCCC1>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N(C)CCCC(=O)O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8f7997eefabb47a8868bf467e90a5a97
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.CC(C)(O)CCCBr>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCC(C)(C)O)cc2)c2ccccc21
ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)O)=O)C.C(=O)([O-])[O-].[K+].[K+].BrCCCC(C)(O)C>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCCCC(C)(C)O)=O)C
[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]([OH:23])[cH:31][cH:32]2)[c:33]2[cH:34][cH:35][cH:36][cH:37][c:38]21.Br[CH2:24][CH2:25][CH2:26][C:27]([CH3:28])([CH3:29])[OH:30]>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.CC(C)(O)CCCBr
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCC(C)(C)O)cc2)c2ccccc21
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Br-[CH2;D2;+0:1]-[C:2]-[C:3].[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[C:3]-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]
79
[{"value": 79.0, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCCCC(C)(C)O)=O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 78.8, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCCCC(C)(C)O)=O)C", "details": "CALCULATEDPERCENTYIELD",...
80
CELSIUS
null
null
(2S,4R)-N-(4-Chloro-phenyl)-N-[1-(4-hydroxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide (0.1 g, 0.23 mmol) was dissolved in DMF (5 mL) at room temperature. K2CO3 (0.317 g, 2.3 mmol) was added. 5-Bromo-2-methyl-pentan-2-ol (0.092 g, 0.51 mmol) was added and the reaction was allowed to heat to 80° C. ov...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HBr
CN(C)C=O
80
null
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.CC(C)(O)CCCBr>CN(C)C=O>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCC(C)(C)O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-cefe76de20e24eb88d668fffd35a3609
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.ClCC1CO1>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCC3CO3)cc2)c2ccccc21
ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)O)=O)C.C(=O)([O-])[O-].[K+].[K+].ClCC1OC1>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCC1OC1)=O)C
[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]([OH:23])[cH:28][cH:29]2)[c:30]2[cH:31][cH:32][cH:33][cH:34][c:35]21.Cl[CH2:24][CH:25]1[CH2:26][O:27]1>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.ClCC1CO1
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCC3CO3)cc2)c2ccccc21
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
O=C(c1ccc(OCC2CO2)cc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Cl-[CH2;D2;+0:1]-[C:2]1-[#8:3]-[C:4]-1.[OH;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[c:7]:[c:6](-[O;H0;D2;+0:5]-[CH2;D2;+0:1]-[C:2]1-[#8:3]-[C:4]-1):[c:8]
98.3
[{"value": 77.0, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCC1OC1)=O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 98.3, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCC1OC1)=O)C", "details": "CALCULATEDPERCENTYIELD", "is_desir...
80
CELSIUS
null
null
(2S,4R)-N-(4-Chloro-phenyl)-N-[1-(4-hydroxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide (0.5 g, 1.14 mmol) was dissolved in DMF at room temperature and K2CO3 (1.26 g, 9.13 mmol) was added. 2-Chloromethyl-oxirane (0.42 g, 4.57 mmol) was added and the reaction was allowed to heat to 80° C. overnight. Th...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccccc1.C1CO1.c1ccc2c(c1)CCC[NH]2
HCl
CN(C)C=O
80
null
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.ClCC1CO1>CN(C)C=O>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCC3CO3)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c6c0cf70711c47f89026ad950f4e6147
COC(=O)C(C)(C)CCCc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(CCCC(C)(C)C(=O)O)cc2)c2ccccc21
COC(C(CCCC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C)(C)C)=O.[OH-].[Na+]>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)CCCC(C(=O)O)(C)C)C)C1=CC=C(C=C1)Cl
C[O:31][C:29]([C:26]([CH2:25][CH2:24][CH2:23][c:22]1[cH:21][cH:20][c:19]([C:17]([N:16]2[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]3[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]3)[c:39]3[c:34]2[cH:35][cH:36][cH:37][cH:38]3)=[O:18])[cH:33][cH:32]1)([CH3:27])[CH3:28])=[O:30]>>[CH3:1][C:2](=[O:3])[N:4](...
COC(=O)C(C)(C)CCCc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(CCCC(C)(C)C(=O)O)cc2)c2ccccc21
null
null
O.CO.O1CCCC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
60
[{"value": 60.0, "product": "C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)CCCC(C(=O)O)(C)C)C)C1=CC=C(C=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 60.0, "product": "C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)CCCC(C(=O)O)(C)C)C)C1=CC=C(C=C1)Cl", "details": "CALCULATEDPE...
60
CELSIUS
null
null
5-(4-{(2S,4R)-4-[acetyl(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenyl)-2,2-dimethyl-pentanoic acid methyl ester (500 mg, 0.89 mmol, 1 eq.) was dissolved in methanol/tetrahydrofuran (2/1) (4 ml). A solution of sodium hydroxide (71 mg, 1.8 mmol, 2 eq.) in water (1 ml) was added and reaction...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
Other
O.CO.O1CCCC1
60
null
COC(=O)C(C)(C)CCCc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1>O.CO.O1CCCC1>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(CCCC(C)(C)C(=O)O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-40a6ccf4648e4083a27814efb89a04c0
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(NC(=O)OCc4ccccc4)cc3)C[C@@H]2C)cc1>>COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(N)cc3)C[C@@H]2C)cc1
C(C)(=O)N(C1=CC=C(C=C1)NC(OCC1=CC=CC=C1)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C>>NC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C
O=C(OCc1ccccc1)[NH:25][c:24]1[cH:23][cH:22][c:21]([N:17]([C@H:16]2[c:15]3[c:10]([cH:11][cH:12][cH:13][cH:14]3)[N:9]([C:7]([c:6]3[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:32][cH:31]3)=[O:8])[C@@H:29]([CH3:30])[CH2:28]2)[C:18]([CH3:19])=[O:20])[cH:27][cH:26]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[N:9]2[c:10]3[cH:11...
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(NC(=O)OCc4ccccc4)cc3)C[C@@H]2C)cc1
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(N)cc3)C[C@@H]2C)cc1
null
[Pd]
CO
Reduction
Hydrogenolysis of amides/imides/carbamates
087b6600ba91d3df931fe6979f2445c192cbfd59e04fd2d8a10f7c7573ac669f
4e549866ec1acadec4c84aaf8495992a28ec78d8ea5ef1b9f44dd843b0dcb7d4
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
O=C(-O-C-c1:c:c:c:c:c:1)-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
null
null
2
HOUR
Benzyl (4-{acetyl[(2S,4R)-1-(4-methoxybenzoyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl]amino}phenyl)carbamate was dissolved in MeOH and was added a catalytic amount of Palladium on Carbon (10%). The system was purged by Hydrogen gas, the subjected to 1 atm of H2 for 2 h. The reaction was quenched with air and filtered...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether
Primary amine
c1ccccc1
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HO-
[Pd].CO
null
2
COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(NC(=O)OCc4ccccc4)cc3)C[C@@H]2C)cc1>[Pd].CO>COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(N)cc3)C[C@@H]2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-40840153529243fdbf17ca5637a03392
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)cc2)c2ccccc21.CS(N)(=O)=O>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)NS(C)(=O)=O)cc2)c2ccccc21
C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCCC(C(=O)O)(C)C)C=C1)C)C1=CC=C(C=C1)Cl.CN(C)C=O.CS(=O)(=O)N>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCCC(C(=O)NS(=O)(=O)C)(C)C)=O)C
O[C:29]([C:26]([CH2:25][CH2:24][O:23][c:22]1[cH:21][cH:20][c:19]([C:17]([N:16]2[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]3[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]3)[c:43]3[c:38]2[cH:39][cH:40][cH:41][cH:42]3)=[O:18])[cH:37][cH:36]1)([CH3:27])[CH3:28])=[O:30].[NH2:31][S:32]([CH3:33])(=[O:34])=[...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)cc2)c2ccccc21.CS(N)(=O)=O
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)NS(C)(=O)=O)cc2)c2ccccc21
null
null
C(Cl)Cl.C(C(=O)Cl)(=O)Cl
Acylation
Carboxylic acid with primary amine to amide
195a412a8235704efe2985cdc18467ba661e632bab7b61944399ecc813e32a09
5e4665bad9c6f58dddd98c5f95e436c640b4c0118b04efea5cd58c7d1755401d
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])(-[C;D1;H3:5])-[C;D1;H3:6].[C;D1;H3:7]-[#16:8](-[NH2;D1;+0:9])(=[O;D1;H0:10])=[O;D1;H0:11]>>[C:4]-[C:3](-[C;D1;H3:5])(-[C;D1;H3:6])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:9]-[#16:8](-[C;D1;H3:7])(=[O;D1;H0:10])=[O;D1;H0:11]
null
[]
null
null
null
null
(2S,4R)-4-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-2,2-dimethyl-butyric acid (200 mg, 0.37 mmol) was dissolved in methylene chloride (5 mL) and oxalyl chloride (2 mL). A single drop of DMF was added, and the mixture was stirred at room temperature until gas evolution...
10.6084/m9.figshare.5104873.v1
null
Sulfonamide.Carboxylic acid
Sulfonamide.Secondary amide
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HO-
C(Cl)Cl.C(C(=O)Cl)(=O)Cl
null
null
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)cc2)c2ccccc21.CS(N)(=O)=O>C(Cl)Cl.C(C(=O)Cl)(=O)Cl>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)NS(C)(=O)=O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-433aac779362428ca7ba64aa1edae43c
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)c2ccc(Cl)cc21.CCc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cn1.COC(=O)c1ccc(Cl)nc1.O=C(Cl)c1cc(C(F)(F)F)cc(C(F)(F)F)c1>>CCc1ccc(C(=O)N2c3ccc(Cl)cc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cn1.CCc1ccc(CCl)cn1
ClC1=NC=C(C(=O)OC)C=C1.FC(C=1C=C(C(=O)N2[C@H](C[C@H](C3=CC(=CC=C23)Cl)N(C(C)=O)C2=CC=C(C=C2)Cl)C)C=C(C1)C(F)(F)F)(F)F.ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C=1C=NC(=CC1)CC)C.FC(C=1C=C(C(=O)Cl)C=C(C1)C(F)(F)F)(F)F>>ClC=1C=C2[C@@H](C[C@@H](N(C2=CC1)C(=O)C=1C=NC(=CC1)CC)C)N(C(C)=O)C1=CC=C(C=C1)Cl.C(C)...
FC(F)(F)c1cc(C(F)(F)F)c[c:6]([C:7](=[O:8])[N:9]2[c:10]3[cH:11][cH:12][c:13]([Cl:14])[cH:15][c:16]3[C@H:17]([N:18]([C:19]([CH3:20])=[O:21])[c:22]3[cH:23][cH:24][c:25]([Cl:26])[cH:27][cH:28]3)[CH2:29][C@@H:30]2[CH3:31])c1.CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)[c:39]2[cH:38][cH:37][c:36]([CH2:35][CH3:34])[n:43][cH:4...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)c2ccc(Cl)cc21.CCc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cn1.COC(=O)c1ccc(Cl)nc1.O=C(Cl)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
CCc1ccc(C(=O)N2c3ccc(Cl)cc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cn1.CCc1ccc(CCl)cn1
null
null
null
C-C Coupling
OtherReaction
94936b50ede0589ceddb51bfd0526e44744ef6bd0a8f1b7daf946455f196bafa
54d9f26861cc63ff190e6c74176f91c87344340754274c573a4ba194b02c5cd4
O=C(c1cccnc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21.c1ccncc1
C-C(=O)-N(-[C@H]1-C-[C@H](-C)-N(-C(=O)-[c;H0;D3;+0:1]2:[c:2]:[c:3]:[c:4]:[#7;a:5]:[c:6]:2)-c2:c:c:c:c:c:2-1)-c1:c:c:c(-Cl):c:c:1.Cl-[c;H0;D3;+0:7]1:[#7;a:8]:[cH;D2;+0:9]:c(-[C;H0;D3;+0:10](=O)-O-[CH3;D1;+0:11]):[cH;D2;+0:12]:[c:13]:1.F-C(-F)(-F)-c1:c:[c;H0;D3;+0:14](-[C:15](=[O;D1;H0:16])-[#7:17](-[C:18])-[c:19]):c:c(-...
null
[]
null
null
null
null
N-{(2S,4R)-6-Chloro-1-[(6-ethylpyridin-3-yl)carbonyl]-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl}-N-(4-chlorophenyl)acetamide was prepared following the procedure described for N-{(2S,4R)-1-[3,5-bis(trifluoromethyl)benzoyl]-6-chloro-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl}-N-(4-chlorophenyl)acetamide substituting 6-ethy...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Trifluoro group.Trifluoro group.Trifluoro group.Trifluoro group.Aromatic halide.Aromatic halide.Ester.Tertiary amide.Tertiary amide
Primary halide
c1ccccc1.c1ccccc1.c1ccncc1.c1ccc2c(c1)CCCN2.c1ccncc1.c1ccccc1
c1ccncc1.c1ccncc1
c1ccncc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2.c1ccncc1
HF
null
null
null
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)c2ccc(Cl)cc21.CCc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cn1.COC(=O)c1ccc(Cl)nc1.O=C(Cl)c1cc(C(F)(F)F)cc(C(F)(F)F)c1>>CCc1ccc(C(=O)N2c3ccc(Cl)cc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cn1.CCc1ccc(CCl)cn1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-853ea3c5ceb945febb40bb8f607ef5c3
COC(=O)C(C)(C)CCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)C3CC3)c3ccc(Cl)cc3)C[C@@H]2C)cc1>>C[C@H]1C[C@@H](N(C(=O)C2CC2)c2ccc(Cl)cc2)c2ccccc2N1C(=O)c1ccc(OCCC(C)(C)C(=O)O)cc1
ClC1=CC=C(C=C1)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCCC(C(=O)OC)(C)C)C=C1)C)C(=O)C1CC1.[OH-].[Na+]>>ClC1=CC=C(C=C1)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCCC(C(=O)O)(C)C)C=C1)C)C(=O)C1CC1
C[O:39][C:37]([C:34]([CH2:33][CH2:32][O:31][c:30]1[cH:29][cH:28][c:27]([C:25]([N:24]2[C@@H:2]([CH3:1])[CH2:3][C@@H:4]([N:5]([C:6](=[O:7])[CH:8]3[CH2:9][CH2:10]3)[c:11]3[cH:12][cH:13][c:14]([Cl:15])[cH:16][cH:17]3)[c:18]3[cH:19][cH:20][cH:21][cH:22][c:23]32)=[O:26])[cH:41][cH:40]1)([CH3:35])[CH3:36])=[O:38]>>[CH3:1][C@H...
COC(=O)C(C)(C)CCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)C3CC3)c3ccc(Cl)cc3)C[C@@H]2C)cc1
C[C@H]1C[C@@H](N(C(=O)C2CC2)c2ccc(Cl)cc2)c2ccccc2N1C(=O)c1ccc(OCCC(C)(C)C(=O)O)cc1
null
null
O.CO.O1CCCC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(c1ccccc1)N1CC[C@@H](N(C(=O)C2CC2)c2ccccc2)c2ccccc21
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
87
[{"value": 87.0, "product": "ClC1=CC=C(C=C1)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCCC(C(=O)O)(C)C)C=C1)C)C(=O)C1CC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 86.9, "product": "ClC1=CC=C(C=C1)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCCC(C(=O)O)(C)C)C=C1)C)C(=O)C1CC1", "details": "CALCULAT...
40
CELSIUS
null
null
Methyl 4-(4-{[(2S,4R)-4-[(4-chlorophenyl)(cyclopropylcarbonyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}phenoxy)-2,2-dimethylbutanoate (100 mg, 0.17 mmol, 1 equ.) was dissolved in methanol/tetrahydrofuran (2/1) (1 ml). A solution of sodium hydroxide (21 mg, 0.51 mmol, 3 eq.) in water (0.5 ml) was added and ...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CC1.c1ccccc1.c1ccc2c(c1)CCC[NH]2.c1ccccc1
Other
O.CO.O1CCCC1
40
null
COC(=O)C(C)(C)CCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(=O)C3CC3)c3ccc(Cl)cc3)C[C@@H]2C)cc1>O.CO.O1CCCC1>C[C@H]1C[C@@H](N(C(=O)C2CC2)c2ccc(Cl)cc2)c2ccccc2N1C(=O)c1ccc(OCCC(C)(C)C(=O)O)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-90e2427c2c1f47b09894c70bbe445f5b
CCc1cc(C(=O)OC)ccc1F>>CCc1cc(C(=O)O)ccc1F
C(C)C=1C=C(C(=O)OC)C=CC1F.[OH-].[Li+]>>FC1=C(C=C(C(=O)O)C=C1)CC
C[O:8][C:6]([c:5]1[cH:4][c:3]([CH2:2][CH3:1])[c:11]([F:12])[cH:10][cH:9]1)=[O:7]>>[CH3:1][CH2:2][c:3]1[cH:4][c:5]([C:6](=[O:7])[OH:8])[cH:9][cH:10][c:11]1[F:12]
CCc1cc(C(=O)OC)ccc1F
CCc1cc(C(=O)O)ccc1F
null
[Pd]
CO.O1CCCC1.O.CO
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccccc1
C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]>>[O;D1;H0:3]=[C:2](-[OH;D1;+0:1])-[c:4]
null
[]
null
null
2
HOUR
(4-fluoro-3-ethylbenzoyl chloride was prepared in 5 steps from 3-bromo-4-fluorobenzoic acid. 3-bromo-4-fluorobenzoic acid was converted to methyl 3-bromo-4-fluorobenzoate by treatment with trimethylsilyl diazomethane (1.5 equivalents) in benzene/methanol (4/1) at room temperature. Subsequent reaction with tributyl(viny...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1
Other
[Pd].CO.O1CCCC1.O.CO
null
2
CCc1cc(C(=O)OC)ccc1F>[Pd].CO.O1CCCC1.O.CO>CCc1cc(C(=O)O)ccc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-53b6a1d374464c7dadaa4a3f7b6367b9
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.CC(C)(CCO)n1ccnc1>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)n3ccnc3)cc2)c2ccccc21
CCOC(=O)/N=N/C(=O)OCC.ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)O)=O)C.N1(C=NC=C1)C(CCO)(C)C.C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=CC=CC=C3>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCCC(C)(C)N1C=NC=C1)=O)C
[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]([OH:23])[cH:34][cH:35]2)[c:36]2[cH:37][cH:38][cH:39][cH:40][c:41]21.O[CH2:24][CH2:25][C:26]([CH3:27])([CH3:28])[n:29]1[cH:30][cH:31][n:32][cH:33]1>>[CH3:1][C:2](...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.CC(C)(CCO)n1ccnc1
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)n3ccnc3)cc2)c2ccccc21
null
null
C1=CC=CC=C1
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
O=C(c1ccc(OCCCn2ccnc2)cc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
O-[CH2;D2;+0:1]-[C:2]-[C:3].[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[C:3]-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]
46
[{"value": 46.0, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCCC(C)(C)N1C=NC=C1)=O)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
5
MINUTE
3-Imidazol-1-yl-3-methyl-butan-1-ol was dissolved in benzene at room temperature with PPh3 (0.088 g, 0.33 mmol) added (2S,4R)-N-(4-chloro-phenyl)-N-[1-(4-hydroxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide (0.133 g, 0.30 mmol) and stirred for 5 min. DEAD (0.058 g, 0.33 mmol) was added and the reaction...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccccc1.c1c[nH]cn1.c1ccc2c(c1)CCC[NH]2
HO-
C1=CC=CC=C1
null
0.083333
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.CC(C)(CCO)n1ccnc1>C1=CC=CC=C1>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)n3ccnc3)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-217d6172dd4a4309820f436cdcba0e57
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCC3CCNCC3)cc2)c2ccccc21.CC=O>>CCN1CCC(COc2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc2)CC1
ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCC1CCNCC1)=O)C.C(C)=O.[BH-](OC(=O)C)(OC(=O)C)OC(=O)C.[Na+]>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCC1CCN(CC1)CC)=O)C
[NH:3]1[CH2:4][CH2:5][CH:6]([CH2:7][O:8][c:9]2[cH:10][cH:11][c:12]([C:13](=[O:14])[N:15]3[c:16]4[cH:17][cH:18][cH:19][cH:20][c:21]4[C@H:22]([N:23]([C:24]([CH3:25])=[O:26])[c:27]4[cH:28][cH:29][c:30]([Cl:31])[cH:32][cH:33]4)[CH2:34][C@@H:35]3[CH3:36])[cH:37][cH:38]2)[CH2:39][CH2:40]1.O=[CH:2][CH3:1]>>[CH3:1][CH2:2][N:3]...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCC3CCNCC3)cc2)c2ccccc21.CC=O
CCN1CCC(COc2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc2)CC1
null
null
ClCCl
Heteroatom Alkylation and Arylation
reductive amination
d0e659bc8d1e29e09a61320b4c537e66ad57335a51368c8bd48de9bdffa59372
2d03f38884b1fbb0c0d6e6f2de31afb25102fec87f347c3a123e064c1bfef0ad
O=C(c1ccc(OCC2CCNCC2)cc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
O=[CH;D2;+0:1]-[C;D1;H3:2].[C:3]-[C:4]-[NH;D2;+0:5]-[C:6]-[C:7]>>[C:3]-[C:4]-[N;H0;D3;+0:5](-[CH2;D2;+0:1]-[C;D1;H3:2])-[C:6]-[C:7]
55
[{"value": 55.0, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCC1CCN(CC1)CC)=O)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The piperdine was reacted with acetaldehyde, Na(OAc)3BH in dichloromethane at room temperature overnight. Then washed with 1N NaOH, dried over MgSO4, filtered and concentrated down. The crude residue was purified by silica gel chromatography (10% methanol/90% dichloromethane) to afford the product (55%). Conditions: Se...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Secondary amine
Tertiary amine
C1CCNCC1
C1CC[NH]CC1
C1CC[NH]CC1.c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
Other
ClCCl
null
null
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCC3CCNCC3)cc2)c2ccccc21.CC=O>ClCCl>CCN1CCC(COc2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-fa1545499cc04897b27dabdb60c8c706
COC(=O)C(C)(C)CCOc1cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)ccc1F>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(F)c(OCCC(C)(C)C(=O)O)c2)c2ccccc21
C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C=1C=CC(=C(OCCC(C(=O)OC)(C)C)C1)F)C)C1=CC=C(C=C1)Cl.[Li+].[OH-]>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C=1C=CC(=C(OCCC(C(=O)O)(C)C)C1)F)C)C1=CC=C(C=C1)Cl
C[O:33][C:31]([C:28]([CH2:27][CH2:26][O:25][c:24]1[c:22]([F:23])[cH:21][cH:20][c:19]([C:17]([N:16]2[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]3[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]3)[c:40]3[c:35]2[cH:36][cH:37][cH:38][cH:39]3)=[O:18])[cH:34]1)([CH3:29])[CH3:30])=[O:32]>>[CH3:1][C:2](=[O:3])[...
COC(=O)C(C)(C)CCOc1cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)ccc1F
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(F)c(OCCC(C)(C)C(=O)O)c2)c2ccccc21
null
null
CO.C1CCOC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
null
[]
null
null
8
HOUR
To the solution of Methyl 4-(5-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}-2-fluorophenoxy)-2,2-dimethylbutanoate in MeOH/THF (1 mL/1 mL) was added excessive LiOH (1N aqueous solution). The reaction mixture was stirred at r.t. for overnight. The reaction was quenched by add...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
Other
CO.C1CCOC1
null
8
COC(=O)C(C)(C)CCOc1cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)ccc1F>CO.C1CCOC1>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(F)c(OCCC(C)(C)C(=O)O)c2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-61d2f884d424442d8dd39ecaf517e5d6
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N(S(C)(=O)=O)S(C)(=O)=O)cc2)c2ccccc21>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(NS(C)(=O)=O)cc2)c2ccccc21
O.C([O-])(O)=O.[Na+].CS(=O)(=O)N(C1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=C(C=C2)Cl)C)C=C1)S(=O)(=O)C.[OH-].[Na+]>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)NS(=O)(=O)C)=O)C
CS(=O)(=O)[N:23]([c:22]1[cH:21][cH:20][c:19]([C:17]([N:16]2[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]3[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]3)[c:35]3[c:30]2[cH:31][cH:32][cH:33][cH:34]3)=[O:18])[cH:29][cH:28]1)[S:24]([CH3:25])(=[O:26])=[O:27]>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N(S(C)(=O)=O)S(C)(=O)=O)cc2)c2ccccc21
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(NS(C)(=O)=O)cc2)c2ccccc21
null
null
O1CCCC1
Reduction
Hydrogenolysis of tertiary amines
de0c360cde7152c6dc8d2dc7689a99d4783d487dca4b5e872fbf9bc8168f99f7
40552f2058ccfb8ff7e827f21cb476a78a40df984798f4706d5812adf64d0001
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-S(=O)(=O)-[N;H0;D3;+0:1](-[c:2](:[c:3]):[c:4])-[#16:5](-[C;D1;H3:6])(=[O;D1;H0:7])=[O;D1;H0:8]>>[C;D1;H3:6]-[#16:5](=[O;D1;H0:7])(=[O;D1;H0:8])-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4]
84.3
[{"value": 76.0, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)NS(=O)(=O)C)=O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 84.3, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)NS(=O)(=O)C)=O)C", "details": "CALCULATEDPERCENTYIELD", "...
null
null
2
DAY
To a solution of N-((2S,4R)-1-{4-[bis(methylsulfonyl)amino]benzoyl}-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)-N-(4-chlorophenyl)acetamide (259 mg, 0.44 mmol) in tetrahydrofuran (5.0 mL) at room temperature was added 1.0 M sodium hydroxide (0.880 mL, 0.88 mmol). The reaction was stirred at room temperature for 2 days. T...
10.6084/m9.figshare.5104873.v1
null
Tertiary amine
Sulfonamide
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HO-
O1CCCC1
null
48
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N(S(C)(=O)=O)S(C)(=O)=O)cc2)c2ccccc21>O1CCCC1>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(NS(C)(=O)=O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8e80d6b8a1c748f68ed40bad6c5176e6
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN)cc2)c2ccccc21.CN1CCC[C@H]1C(=O)O>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1CC(C)N(C(=O)c2ccc(OCCCNC(=O)[C@@H]3CCCN3C)cc2)c2ccccc21
NCCCOC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=C(C=C2)Cl)C)C=C1.CN1[C@H](C(=O)O)CCC1.C(CCl)Cl>>C(C)(=O)N([C@@H]1CC(N(C2=CC=CC=C12)C(=O)C1=CC=C(OCCCNC(=O)[C@H]2N(CCC2)C)C=C1)C)C1=CC=C(C=C1)Cl
[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]([O:23][CH2:24][CH2:25][CH2:26][NH2:27])[cH:36][cH:37]2)[c:38]2[cH:39][cH:40][cH:41][cH:42][c:43]21.O[C:28](=[O:29])[C@@H:30]1[CH2:31][CH2:32][CH2:33][N:34]1[CH3:...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN)cc2)c2ccccc21.CN1CCC[C@H]1C(=O)O
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1CC(C)N(C(=O)c2ccc(OCCCNC(=O)[C@@H]3CCCN3C)cc2)c2ccccc21
null
null
N1=CC=CC=C1.C(Cl)Cl
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(NCCCOc1ccc(C(=O)N2CC[C@@H](Nc3ccccc3)c3ccccc32)cc1)[C@@H]1CCCN1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])-[#7:5](-[C;D1;H3:6])-[C:7].[C:8]-[C:9]-[NH2;D1;+0:10]>>[C:8]-[C:9]-[NH;D2;+0:10]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])-[#7:5](-[C;D1;H3:6])-[C:7]
null
[]
null
null
1
HOUR
(2S,4R)-N-{1-[4-(3-Amino-propoxy)-benzoyl]-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl}-N-(4-chloro-phenyl)-acetamide (100 mg, 0.204 mmol) was dissolved in methylene chloride (2 mL) and pyridine (2 mL). N-methyl proline (33 mg, 0.255 mmol) and EDC (63 mg, 0.255 mmol) were added and the reaction was stirred for 1 hour. Th...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccccc1.C1CC[NH]C1.c1ccc2c(c1)CCC[NH]2
HO-
N1=CC=CC=C1.C(Cl)Cl
null
1
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN)cc2)c2ccccc21.CN1CCC[C@H]1C(=O)O>N1=CC=CC=C1.C(Cl)Cl>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1CC(C)N(C(=O)c2ccc(OCCCNC(=O)[C@@H]3CCCN3C)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-98f502800b7d437cb016572d856ab44a
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)cc2)c2ccccc21>>CC(=O)N(c1ccc(Cl)cc1)[C@H]1C[C@@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)cc2)c2ccccc21
C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCCC(C(=O)O)(C)C)C=C1)C)C1=CC=C(C=C1)Cl.ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OC)=O)C>>C(C)(=O)N([C@H]1C[C@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCCC(C(=O)O)(C)C)C=C1)C)C1=CC=C(C=C1)Cl
[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]([O:23][CH2:24][CH2:25][C:26]([CH3:27])([CH3:28])[C:29](=[O:30])[OH:31])[cH:32][cH:33]2)[c:34]2[cH:35][cH:36][cH:37][cH:38][c:39]21>>[CH3:1][C:2](=[O:3])[N:4]([c:...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)cc2)c2ccccc21
CC(=O)N(c1ccc(Cl)cc1)[C@H]1C[C@@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)cc2)c2ccccc21
null
null
null
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
O=C(c1ccccc1)N1CC[C@H](Nc2ccccc2)c2ccccc21
null
null
[]
null
null
null
null
4-(4-{[(2R,4S)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}phenoxy)-2,2-dimethylbutanoic acid was prepared following the procedure to prepare 4-(4-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydro-quinolin-1(2H)-yl]carbonyl}phenoxy)-2,2-dimethylbutanoic acid, substituting...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
null
null
null
null
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)cc2)c2ccccc21>>CC(=O)N(c1ccc(Cl)cc1)[C@H]1C[C@@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-12ca8a4bd50c4230a6f0da0d9d204f48
CC(=O)CCCc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(CCCC(C)(C)O)cc2)c2ccccc21
ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)CCCC(C)=O)=O)C.C[Mg+].[Br-]>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)CCCC(C)(C)O)=O)C
[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]([CH2:23][CH2:24][CH2:25][C:26]([CH3:27])=[O:29])[cH:30][cH:31]2)[c:32]2[cH:33][cH:34][cH:35][cH:36][c:37]21>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([C...
CC(=O)CCCc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(CCCC(C)(C)O)cc2)c2ccccc21
null
null
C1CCOC1
Miscellaneous
OtherReaction
7e61014f084ef66fe8691c8f1abaf493e11079effe9d87ae329e041d937b8b3a
8811b4d793f7cfa9f0f1f47a008648edabb54f371f76dfa680dd5b2e1564c6c5
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
[C:1]-[C:2]-[C;H0;D3;+0:3](-[C;D1;H3:4])=[O;H0;D1;+0:5]>>[C:1]-[C:2]-[C;H0;D4;+0:3](-[C;D1;H3:4])(-[C;D1;H3:6])-[OH;D1;+0:5]
40
[{"value": 40.0, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)CCCC(C)(C)O)=O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 39.0, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)CCCC(C)(C)O)=O)C", "details": "CALCULATEDPERCENTYIELD", "...
0
CELSIUS
2
HOUR
To a solution of N-(4-chlorophenyl)-N-((2S,4R)-2-methyl-1-(4-(4-oxopentyl)benzoyl)-1,2,3,4-tetrahydroquinolin-4-yl)acetamide (40 mg, 0.079 mmol) in THF (2 mL), was added MeMgBr (68 uL, 0.095 mmol, 1.4 M solution in THF) at 0° C. The mixture was stirred at 0° C. for 2 h. After quenching with sat. NH4Cl solution, the mix...
10.6084/m9.figshare.5104873.v1
null
Ketone
Tertiary alcohol
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
Other
C1CCOC1
0
2
CC(=O)CCCc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1>C1CCOC1>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(CCCC(C)(C)O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b2b9ea51be7b485ea06c0c3cbdacbeab
COc1c(F)cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1F>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc(F)c(O)c(F)c2)c2ccccc21
ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC(=C(C(=C1)F)OC)F)=O)C.B(Br)(Br)Br>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC(=C(C(=C1)F)O)F)=O)C
C[O:24][c:23]1[c:21]([F:22])[cH:20][c:19]([C:17]([N:16]2[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]3[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]3)[c:33]3[c:28]2[cH:29][cH:30][cH:31][cH:32]3)=[O:18])[cH:27][c:25]1[F:26]>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:...
COc1c(F)cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1F
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc(F)c(O)c(F)c2)c2ccccc21
null
null
ClCCl
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[OH;D1;+0:1]-[c:2](:[c:3]):[c:4]
78.7
[{"value": 78.0, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC(=C(C(=C1)F)O)F)=O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 78.7, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC(=C(C(=C1)F)O)F)=O)C", "details": "CALCULATEDPERCENTYIELD", "is_desir...
null
null
null
null
N-(4-chlorophenyl)-N-[(2S,4R)-1-(3,5-difluoro-4-methoxybenzoyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl]acetamide (200 mg, 0.41 mmol) was dissolved in dichloromethane and a solution of BBr3 (1.0 M in dichloromethane, 3.0 mL) was added; the reaction mixture was stirred at room temperature for until no starting material...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
Other
ClCCl
null
null
COc1c(F)cc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1F>ClCCl>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2cc(F)c(O)c(F)c2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-dc52b191e34d4cd99f8b626c4f71e0c6
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN)cc2)c2ccccc21.COC(=O)Cl>>COC(=O)NCCCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
NCCCOC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=C(C=C2)Cl)C)C=C1.ClC(=O)OC>>COC(NCCCOC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C)=O
[NH2:5][CH2:6][CH2:7][CH2:8][O:9][c:10]1[cH:11][cH:12][c:13]([C:14](=[O:15])[N:16]2[c:17]3[cH:18][cH:19][cH:20][cH:21][c:22]3[C@H:23]([N:24]([C:25]([CH3:26])=[O:27])[c:28]3[cH:29][cH:30][c:31]([Cl:32])[cH:33][cH:34]3)[CH2:35][C@@H:36]2[CH3:37])[cH:38][cH:39]1.Cl[C:3]([O:2][CH3:1])=[O:4]>>[CH3:1][O:2][C:3](=[O:4])[NH:5]...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN)cc2)c2ccccc21.COC(=O)Cl
COC(=O)NCCCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
null
null
C(Cl)Cl
Protection
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
038720aa61a7efa0f2a9ee6f2e0adf63a9ffdc2be4697c11a6215baef34f97b2
205f353513ce9506ab61831799da8fb73ec2ef5cfa927664496d3ce72c438860
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[C;D1;H3:4].[C:5]-[C:6]-[NH2;D1;+0:7]>>[C:5]-[C:6]-[NH;D2;+0:7]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[C;D1;H3:4]
52
[{"value": 52.0, "product": "COC(NCCCOC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 43.0, "product": "COC(NCCCOC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C)=O", "details": "CALCULATEDPERCENTYIELD", "is...
null
null
18
HOUR
(2S,4R)-N-{1-[4-(3-Amino-propoxy)-benzoyl]-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl}-N-(4-chloro-phenyl)-acetamide (150 mg, 0.30 mmol) was dissolved in DCM (1 mL). To this solution was added TEA (36.4 mg, 0.36 mmol) followed by methyl chloroformate (34 mg, 0.36 mmol). The reaction mixture was stirred at room temperatu...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Ether.Primary amine
Carbamic ester
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HCl
C(Cl)Cl
null
18
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN)cc2)c2ccccc21.COC(=O)Cl>C(Cl)Cl>COC(=O)NCCCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-02d179395a7c42c29f7a5b41e2967e41
COC(=O)c1ccc(COc2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc2)o1>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCc3ccc(C(=O)O)o3)cc2)c2ccccc21
COC(=O)C=1OC(=CC1)COC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C.C(C)O.[OH-].[Na+]>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCC2=CC=C(O2)C(=O)O)C=C1)C)C1=CC=C(C=C1)Cl
C[O:31][C:29]([c:28]1[cH:27][cH:26][c:25]([CH2:24][O:23][c:22]2[cH:21][cH:20][c:19]([C:17]([N:16]3[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]4[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]4)[c:40]4[c:35]3[cH:36][cH:37][cH:38][cH:39]4)=[O:18])[cH:34][cH:33]2)[o:32]1)=[O:30]>>[CH3:1][C:2](=[O:3])[N:4](...
COC(=O)c1ccc(COc2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc2)o1
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCc3ccc(C(=O)O)o3)cc2)c2ccccc21
null
null
O1CCCC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(c1ccc(OCc2ccco2)cc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[#8;a:5]>>[#8;a:5]:[c:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1]
null
[]
null
null
4
HOUR
(2S,4R)-5-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxymethyl)-furan-2-carboxylic acid methyl ester (0.145 g, 0.25 mmol) was hydrolyzed to the acid by dissolving in tetrahydrofuran and ethanol and sodium hydroxide (1N) was added. The mixture was stirred at room temperature...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.c1ccccc1.c1ccoc1.c1ccc2c(c1)CCC[NH]2
Other
O1CCCC1
null
4
COC(=O)c1ccc(COc2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc2)o1>O1CCCC1>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCc3ccc(C(=O)O)o3)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-48311e6822004b5fb134fa57b17d727d
CC(N)=O.COC(=O)C(=C[O-])C(OC)OC>>COC(=O)c1cnc(C)nc1
Cl.C(C)(=O)N.COC(C(=C[O-])C(=O)OC)OC.[Na+].CN(C=O)C>>CC1=NC=C(C=N1)C(=O)OC
O=[C:8]([CH3:9])[NH2:10].CO[CH:6](OC)[C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:11][O-]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][n:7][c:8]([CH3:9])[n:10][cH:11]1
CC(N)=O.COC(=O)C(=C[O-])C(OC)OC
COC(=O)c1cnc(C)nc1
null
null
null
Aromatic Heterocycle Formation
OtherReaction
c99c005b9407326da56e76b50f4dd84c25b6e915d5663e90eda36909527618cf
508036d318a8048f2d7ac8fdf8bbcc4daff877d5b758b7becdb5bd510dcca62d
c1cncnc1
C-O-[CH;D3;+0:1](-O-C)-[C;H0;D3;+0:2](=[CH;D2;+0:3]-[O-])-[C:4](=[O;D1;H0:5])-[#8:6]-[C;D1;H3:7].O=[C;H0;D3;+0:8](-[C;D1;H3:9])-[NH2;D1;+0:10]>>[C;D1;H3:7]-[#8:6]-[C:4](=[O;D1;H0:5])-[c;H0;D3;+0:2]1:[cH;D2;+0:3]:[n;H0;D2;+0:10]:[c;H0;D3;+0:8](-[C;D1;H3:9]):[#7;a:11]:[cH;D2;+0:1]:1
null
[]
100
CELSIUS
null
null
N-(4-chlorophenyl)-N-{(2S,4R)-2-methyl-1-[(2-methylpyrimidin-5-yl)carbonyl]-1,2,3,4-tetrahydroquinolin-4-yl}acetamide was prepared following general procedure H, substituting 2-methylpyrimidine-5-carbonyl chloride for 6-trifluoromethyl nicotinyl chloride. (2-methylpyrimidine-5-carbonyl chloride was prepared in four ste...
10.6084/m9.figshare.5104873.v1
null
Ester.Ether.Ether.Primary amide
Ester
null
c1cncnc1
c1cncnc1
HO-
null
100
null
CC(N)=O.COC(=O)C(=C[O-])C(OC)OC>>COC(=O)c1cnc(C)nc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3975f0ddc3c24bc78b568678041c3aa4
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.CCOC(=O)CCCBr>>CCOC(=O)CCCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)O)=O)C.C(=O)([O-])[O-].[K+].[K+].C(C)OC(CCCBr)=O>>C(C)OC(CCCOC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C)=O
[OH:9][c:10]1[cH:11][cH:12][c:13]([C:14](=[O:15])[N:16]2[c:17]3[cH:18][cH:19][cH:20][cH:21][c:22]3[C@H:23]([N:24]([C:25]([CH3:26])=[O:27])[c:28]3[cH:29][cH:30][c:31]([Cl:32])[cH:33][cH:34]3)[CH2:35][C@@H:36]2[CH3:37])[cH:38][cH:39]1.Br[CH2:8][CH2:7][CH2:6][C:4]([O:3][CH2:2][CH3:1])=[O:5]>>[CH3:1][CH2:2][O:3][C:4](=[O:5...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.CCOC(=O)CCCBr
CCOC(=O)CCCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Br-[CH2;D2;+0:1]-[C:2]-[C:3]-[C:4](-[#8:5])=[O;D1;H0:6].[OH;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[#8:5]-[C:4](=[O;D1;H0:6])-[C:3]-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:7]-[c:8](:[c:9]):[c:10]
null
[]
80
CELSIUS
null
null
(2S,4R)-N-(4-Chloro-phenyl)-N-[1-(4-hydroxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide was dissolved in DMF at room temperature and K2CO3 was added. Ethyl-4-bromobutyrate was added and the reaction was allowed to heat to 80° C. overnight. The reaction mixture was concentrated in vacuo. The residue wa...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HBr
CN(C)C=O
80
null
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.CCOC(=O)CCCBr>CN(C)C=O>CCOC(=O)CCCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3fa66ee1848241f38ef8c6c545005537
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.COC(=O)c1cccc(CBr)c1>>COC(=O)c1cccc(COc2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc2)c1
ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)O)=O)C.C(=O)([O-])[O-].[Cs+].[Cs+].BrCC=1C=C(C(=O)OC)C=CC1>>COC(C1=CC(=CC=C1)COC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C)=O
[OH:11][c:12]1[cH:13][cH:14][c:15]([C:16](=[O:17])[N:18]2[c:19]3[cH:20][cH:21][cH:22][cH:23][c:24]3[C@H:25]([N:26]([C:27]([CH3:28])=[O:29])[c:30]3[cH:31][cH:32][c:33]([Cl:34])[cH:35][cH:36]3)[CH2:37][C@@H:38]2[CH3:39])[cH:40][cH:41]1.Br[CH2:10][c:9]1[cH:8][cH:7][cH:6][c:5]([C:3]([O:2][CH3:1])=[O:4])[cH:42]1>>[CH3:1][O:...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.COC(=O)c1cccc(CBr)c1
COC(=O)c1cccc(COc2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc2)c1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
O=C(c1ccc(OCc2ccccc2)cc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[OH;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[c:7]:[c:6](-[O;H0;D2;+0:5]-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4]):[c:8]
54.4
[{"value": 54.0, "product": "COC(C1=CC(=CC=C1)COC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 54.4, "product": "COC(C1=CC(=CC=C1)COC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C)=O", "details": "CALCULAT...
null
null
18
HOUR
(2S,4R)-N-(4-Chloro-phenyl)-N-[1-(4-hydroxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide (150 mg, 0.35 mmol) was dissolved in DMF (5 mL) at room temperature. Cs2CO3 (283 mg, 0.87 mmol) was added followed by methyl 3-(bromomethyl)benzoate (119 mg, 0.52 mmol) and the reaction was stirred at room temperat...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HBr
CN(C)C=O
null
18
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.COC(=O)c1cccc(CBr)c1>CN(C)C=O>COC(=O)c1cccc(COc2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc2)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4b58686b737a43c9820eb1d963663eba
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OS(=O)(=O)C(F)(F)F)cc2)c2ccccc21.CCOC(=O)C1CCNCC1>>CCOC(=O)C1CCN(c2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc2)CC1
C(C)OC(=O)C1CCNCC1.C(=O)([O-])[O-].[Cs+].[Cs+].C=1C=CC(=CC1)P(C=2C=CC=CC2)C3=CC=C4C=CC=CC4=C3C5=C6C=CC=CC6=CC=C5P(C=7C=CC=CC7)C=8C=CC=CC8.C1COCCOCCOCCOCCOCCO1.C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)OS(=O)(=O)C(F)(F)F)C)C1=CC=C(C=C1)Cl>>C(C)OC(=O)C1CCN(CC1)C1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12...
O=S(=O)(O[c:10]1[cH:11][cH:12][c:13]([C:14](=[O:15])[N:16]2[c:17]3[cH:18][cH:19][cH:20][cH:21][c:22]3[C@H:23]([N:24]([C:25]([CH3:26])=[O:27])[c:28]3[cH:29][cH:30][c:31]([Cl:32])[cH:33][cH:34]3)[CH2:35][C@@H:36]2[CH3:37])[cH:38][cH:39]1)C(F)(F)F.[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]1[CH2:7][CH2:8][NH:9][CH2:40][CH2:41]...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OS(=O)(=O)C(F)(F)F)cc2)c2ccccc21.CCOC(=O)C1CCNCC1
CCOC(=O)C1CCN(c2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc2)CC1
null
C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd]
C1(=CC=CC=C1)C
Heteroatom Alkylation and Arylation
Alkylation of amines
f949f1d3fd566ba42e2236794c8fa62f2dccce09ff5ca665dca94a2a29579577
9a1a0c2e1b87bdf69534c723b7058cd90b31cce176c7a3bc658b2756600b117c
O=C(c1ccc(N2CCCCC2)cc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
F-C(-F)(-F)-S(=O)(=O)-O-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C:6]-[C:7]-[NH;D2;+0:8]-[C:9]-[C:10]>>[C:6]-[C:7]-[N;H0;D3;+0:8](-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5])-[C:9]-[C:10]
null
[]
null
null
null
null
(2S,4R)-1-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenyl)-piperidine-4-carboxylic acid ethyl ester was prepared from (2S,4R)-trifluoro-methanesulfonic acid 4-{4-[acetyl(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenyl ester by adding piperidine-4-...
10.6084/m9.figshare.5104873.v1
null
Triflate.Secondary amine
Tertiary amine
c1ccccc1.C1CCNCC1
C1CC[NH]CC1.c1ccccc1
C1CC[NH]CC1.c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
TfOH.HO-
C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd].C1(=CC=CC=C1)C
null
null
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OS(=O)(=O)C(F)(F)F)cc2)c2ccccc21.CCOC(=O)C1CCNCC1>C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd].C1(=CC=CC=C1)C>CCOC(=O)C1CCN(c2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc...
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-46d7c213297442b69d3385686280f83d
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN)cc2)c2ccccc21.O=C(Cl)OCCBr>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN3CCOC3=O)cc2)c2ccccc21
C(=O)([O-])[O-].[Cs+].[Cs+].C(C)N(CC)CC.NCCCOC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=C(C=C2)Cl)C)C=C1.BrCCOC(=O)Cl>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCCCN1C(OCC1)=O)=O)C
[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]([O:23][CH2:24][CH2:25][CH2:26][NH2:27])[cH:33][cH:34]2)[c:35]2[cH:36][cH:37][cH:38][cH:39][c:40]21.Cl[C:31]([O:30][CH2:29][CH2:28]Br)=[O:32]>>[CH3:1][C:2](=[O:3]...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN)cc2)c2ccccc21.O=C(Cl)OCCBr
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN3CCOC3=O)cc2)c2ccccc21
null
null
C(Cl)Cl.CN(C)C=O
Protection
OtherReaction
15613fb2a10be402bb909c91fd72914a5bd3a21a9fe5a928a138d607049bdc15
2c78a61345fd52f9bd102038239c266d368f2005df51acc4baccc29a58dd2e3c
O=C1OCCN1CCCOc1ccc(C(=O)N2CC[C@@H](Nc3ccccc3)c3ccccc32)cc1
Br-[CH2;D2;+0:1]-[C:2]-[#8:3]-[C;H0;D3;+0:4](-Cl)=[O;D1;H0:5].[C:6]-[C:7]-[NH2;D1;+0:8]>>[C:6]-[C:7]-[N;H0;D3;+0:8]1-[CH2;D2;+0:1]-[C:2]-[#8:3]-[C;H0;D3;+0:4]-1=[O;D1;H0:5]
null
[]
null
null
1
HOUR
(2S,4R)-N-{1-[4-(3-Amino-propoxy)-benzoyl]-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl}-N-(4-chloro-phenyl)-acetamide (50 mg, 0.102 mmol) was dissolved in methylene chloride (3 mL) and triethylamine (0.150 mL, 1.08 mmol) and cooled to −40° C. 2-Bromoethylchloroformate (0.016 mL, 0.153 mmol) was added and the reaction was...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary halide.Ether.Primary amine
Carbamic ester.Ether
null
C1COC[NH]1
c1ccccc1.c1ccccc1.C1COC[NH]1.c1ccc2c(c1)CCC[NH]2
HCl.Br-
C(Cl)Cl.CN(C)C=O
null
1
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN)cc2)c2ccccc21.O=C(Cl)OCCBr>C(Cl)Cl.CN(C)C=O>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN3CCOC3=O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-20fa5cb7d0a742e587ae4f600aa59609
CC(=O)N(c1ccc(Cl)cc1)C1CC(C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)cc2)c2ccccc21>>CC(=O)N(c1ccccc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)cc2)c2ccccc21
C(C)(=O)N(C1CC(N(C2=CC=CC=C12)C(=O)C1=CC=C(OCCC(C(=O)O)(C)C)C=C1)C)C1=CC=C(C=C1)Cl>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCCC(C(=O)O)(C)C)C=C1)C)C1=CC=CC=C1
Cl[c:8]1[cH:7][cH:6][c:5]([N:4]([C:2]([CH3:1])=[O:3])[CH:11]2[CH2:12][CH:13]([CH3:14])[N:15]([C:16](=[O:17])[c:18]3[cH:19][cH:20][c:21]([O:22][CH2:23][CH2:24][C:25]([CH3:26])([CH3:27])[C:28](=[O:29])[OH:30])[cH:31][cH:32]3)[c:33]3[cH:34][cH:35][cH:36][cH:37][c:38]32)[cH:10][cH:9]1>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6...
CC(=O)N(c1ccc(Cl)cc1)C1CC(C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)cc2)c2ccccc21
CC(=O)N(c1ccccc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)cc2)c2ccccc21
null
[Pd]
C(C)O
Functional Group Interconversion
Aromatic dehalogenation
b66818d3926a4463fb8e1c3d4a89e94e47b4d46960d4bdb7bcfbeeec427cfd4e
56de34d4a44cb25d9380269ee5e138b0f24b40a3a0db22c5508049dc775a861f
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Cl-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]>>[c:5]:[c:4]:[cH;D2;+0:1]:[c:2]:[c:3]
null
[]
null
null
3
HOUR
4-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-2,2-dimethyl-butyric acid (300 mg, 0.545 mmol) was dissolved in ethanol. Pd/C (10% Palladium) was added, followed by H2 gas (1 atm-balloon). After 3 hours, the reaction mixture was filtered and concentrated. The crude residu...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
Other
[Pd].C(C)O
null
3
CC(=O)N(c1ccc(Cl)cc1)C1CC(C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)cc2)c2ccccc21>[Pd].C(C)O>CC(=O)N(c1ccccc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCC(C)(C)C(=O)O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-41a8cfe9bf9b4d32a4294e6f1769bfda
CCOC(=O)[C@H](F)Oc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)CC2C)cc1>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1CC(C)N(C(=O)c2ccc(O[C@@H](F)C(=O)O)cc2)c2ccccc21
C(C)OC([C@H](F)OC1=CC=C(C=C1)C(=O)N1C(C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C)=O.[OH-].[K+]>>C(C)(=O)N([C@@H]1CC(N(C2=CC=CC=C12)C(=O)C1=CC=C(O[C@H](C(=O)O)F)C=C1)C)C1=CC=C(C=C1)Cl
CC[O:28][C:26]([C@@H:24]([O:23][c:22]1[cH:21][cH:20][c:19]([C:17]([N:16]2[CH:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]3[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]3)[c:36]3[c:31]2[cH:32][cH:33][cH:34][cH:35]3)=[O:18])[cH:30][cH:29]1)[F:25])=[O:27]>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:...
CCOC(=O)[C@H](F)Oc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)CC2C)cc1
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1CC(C)N(C(=O)c2ccc(O[C@@H](F)C(=O)O)cc2)c2ccccc21
null
null
CO.C1CCOC1
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
null
[]
null
null
1
HOUR
(2S,4R)-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-fluoro-acetic acid ethyl ester (100 mg) was dissolved in methanol/THF (1:1, 5 mL), and potassium hydroxide (1.0N, 1 mL) was added. After 1 hour, the reaction was acidified and extracted with methylene chloride. The org...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
Other
CO.C1CCOC1
null
1
CCOC(=O)[C@H](F)Oc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)CC2C)cc1>CO.C1CCOC1>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1CC(C)N(C(=O)c2ccc(O[C@@H](F)C(=O)O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-706040e5038f4dac820eb79bab8c39b3
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.CCOC(=O)C1CCC(O)CC1>>CCOC(=O)C1CCC(Oc2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc2)CC1
C(C)OC(=O)C1CCC(CC1)O.ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)O)=O)C.N(=NC(=O)OCC)C(=O)OCC.C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=CC=CC=C3>>C(C)OC(=O)C1CCC(CC1)OC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C
O[c:11]1[cH:12][cH:13][c:14]([C:15](=[O:16])[N:17]2[c:18]3[cH:19][cH:20][cH:21][cH:22][c:23]3[C@H:24]([N:25]([C:26]([CH3:27])=[O:28])[c:29]3[cH:30][cH:31][c:32]([Cl:33])[cH:34][cH:35]3)[CH2:36][C@@H:37]2[CH3:38])[cH:39][cH:40]1.[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]1[CH2:7][CH2:8][CH:9]([OH:10])[CH2:41][CH2:42]1>>[CH3:...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.CCOC(=O)C1CCC(O)CC1
CCOC(=O)C1CCC(Oc2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc2)CC1
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
de817abd28aa0a6201a692784d613d548e53f67c49ed49b6eff382c8e9e7a9e4
776ba735002e33225fbc578943016110c2c43efefd97bfeea4ec3cc2e2e1532f
O=C(c1ccc(OC2CCCCC2)cc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
O-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C:6]-[C:7](-[OH;D1;+0:8])-[C:9]>>[C:6]-[C:7](-[O;H0;D2;+0:8]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5])-[C:9]
37
[{"value": 37.0, "product": "C(C)OC(=O)C1CCC(CC1)OC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 36.9, "product": "C(C)OC(=O)C1CCC(CC1)OC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C", "details": "CALCULATED...
0
CELSIUS
10
MINUTE
To a solution of diethyl azodicarboxylate (120 mg) in 5 ml THF at 0° C., was added PPh3 (181 mg). The mixture was stirred for 10 min at 0° C. Then (2S,4R)-N-(4-Chloro-phenyl)-N-[1-(4-hydroxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide (200 mg) was added. The mixture was stirred for 20 min at 0° C. 4-H...
10.6084/m9.figshare.5104873.v1
null
Secondary alcohol.Aromatic alcohol
Ether
c1ccccc1
c1ccccc1
C1CCCCC1.c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HO-
C1CCOC1
0
0.166667
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.CCOC(=O)C1CCC(O)CC1>C1CCOC1>CCOC(=O)C1CCC(Oc2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-18b6d17178be4e53895593555fe05479
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.COC(=O)[C@@H]1CCC[C@H]1CO>>COC(=O)C1CCCC1COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
CCOC(=O)/N=N/C(=O)OCC.ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)O)=O)C.COC(=O)[C@H]1[C@@H](CCC1)CO.C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=CC=CC=C3>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCC2C(CCC2)C(=O)OC)C=C1)C)C1=CC=C(C=C1)Cl
O[c:12]1[cH:13][cH:14][c:15]([C:16](=[O:17])[N:18]2[c:19]3[cH:20][cH:21][cH:22][cH:23][c:24]3[C@H:25]([N:26]([C:27]([CH3:28])=[O:29])[c:30]3[cH:31][cH:32][c:33]([Cl:34])[cH:35][cH:36]3)[CH2:37][C@@H:38]2[CH3:39])[cH:40][cH:41]1.[CH3:1][O:2][C:3](=[O:4])[C@@H:5]1[CH2:6][CH2:7][CH2:8][C@H:9]1[CH2:10][OH:11]>>[CH3:1][O:2]...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.COC(=O)[C@@H]1CCC[C@H]1CO
COC(=O)C1CCCC1COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
null
null
C1(=CC=CC=C1)C
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
8915084acbaaf997bf0f89ff5187cb2f89c25dc683fffc57b3391298c8430dd9
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
O=C(c1ccc(OCC2CCCC2)cc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
O-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C:6]-[C:7]-[OH;D1;+0:8]>>[C:6]-[C:7]-[O;H0;D2;+0:8]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]
90.7
[{"value": 90.0, "product": "C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCC2C(CCC2)C(=O)OC)C=C1)C)C1=CC=C(C=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 90.7, "product": "C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCC2C(CCC2)C(=O)OC)C=C1)C)C1=CC=C(C=C1)Cl", "details": "CALCULAT...
null
null
18
HOUR
Trans-2-Hydroxymethyl-cyclopentanecarboxylic acid methyl ester (0.127 g, 0.81 mmol) was dissolved in 10 ml toluene at room temperature with PPh3 (0.211 g, 0.81 mmol), then added N-(4-chlorophenyl)-N-[(2S,4R)-1-(4-hydroxybenzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]acetamide (0.1 g, 0.23 mmol) and stirred for 5 mi...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
c1ccccc1
c1ccccc1
C1CCCC1.c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HO-
C1(=CC=CC=C1)C
null
18
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.COC(=O)[C@@H]1CCC[C@H]1CO>C1(=CC=CC=C1)C>COC(=O)C1CCCC1COc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9353f8dd2c2e46cfadafb8bff33b9e85
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCC3CCCC3C(=O)[O-])cc2)c2ccccc21>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OC[C@@H]3CCC[C@H]3C(=O)O)cc2)c2ccccc21
C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCC2C(CCC2)C(=O)[O-])C=C1)C)C1=CC=C(C=C1)Cl.C([O-])([O-])=O.[K+].[K+]>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OC[C@H]2[C@@H](CCC2)C(=O)O)C=C1)C)C1=CC=C(C=C1)Cl
[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]([O:23][CH2:24][CH:25]3[CH2:26][CH2:27][CH2:28][CH:29]3[C:30](=[O:31])[O-:32])[cH:33][cH:34]2)[c:35]2[cH:36][cH:37][cH:38][cH:39][c:40]21>>[CH3:1][C:2](=[O:3])[N:...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCC3CCCC3C(=O)[O-])cc2)c2ccccc21
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OC[C@@H]3CCC[C@H]3C(=O)O)cc2)c2ccccc21
null
null
CO
Reduction
Carboxylate to carboxylic acid
65edb34f59b888c9ecb87d6c8e9fd76d082de6afc49403d96c457f834c73148e
222e2311064b3cb906d6bdeba44711f5dada050c096bbbcc7b35038975f228e8
O=C(c1ccc(OCC2CCCC2)cc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
[C:1]-[C:2](-[O-;H0;D1:3])=[O;D1;H0:4]>>[C:1]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:3]
10
[{"value": 10.0, "product": "C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OC[C@H]2[C@@H](CCC2)C(=O)O)C=C1)C)C1=CC=C(C=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}]
null
null
2
DAY
2-[(4-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}phenoxy)methyl]cyclopentanecarboxylate was hydrolyzed to the acid by dissolving in 5 ml methanol and potassium carbonate (0.100 g in 4 ml water) was added. The mixture was stirred for 2 days. The mixture was cooled to room te...
10.6084/m9.figshare.5104873.v1
null
null
Carboxylic acid
null
null
c1ccccc1.c1ccccc1.C1CCCC1.c1ccc2c(c1)CCC[NH]2
null
CO
null
48
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCC3CCCC3C(=O)[O-])cc2)c2ccccc21>CO>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OC[C@@H]3CCC[C@H]3C(=O)O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ff72a5a95c5149c4a3fe7f172e5afa93
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN)cc2)c2ccccc21.C[Si](C)(C)N=C=O>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCNC(N)=O)cc2)c2ccccc21
NCCCOC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=C(C=C2)Cl)C)C=C1.C[Si](C)(C)N=C=O>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCCCNC(=O)N)=O)C
[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]([O:23][CH2:24][CH2:25][CH2:26][NH2:27])[cH:31][cH:32]2)[c:33]2[cH:34][cH:35][cH:36][cH:37][c:38]21.C[Si](C)(C)[N:29]=[C:28]=[O:30]>>[CH3:1][C:2](=[O:3])[N:4]([c:...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN)cc2)c2ccccc21.C[Si](C)(C)N=C=O
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCNC(N)=O)cc2)c2ccccc21
null
null
C(Cl)Cl
Acylation
OtherReaction
6a5835c8b8db4f5aab8dd346fe49f2c81431cc20bacbaaab23b789ee31cca635
6bd8ab6a1c9de6e6b254509d33e097f855d6773ea4cd727c3f1a12189fe3db41
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-[Si](-C)(-C)-[N;H0;D2;+0:1]=[C;H0;D2;+0:2]=[O;D1;H0:3].[C:4]-[C:5]-[NH2;D1;+0:6]>>[C:4]-[C:5]-[NH;D2;+0:6]-[C;H0;D3;+0:2](-[NH2;D1;+0:1])=[O;D1;H0:3]
17
[{"value": 17.0, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCCCNC(=O)N)=O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 16.8, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCCCNC(=O)N)=O)C", "details": "CALCULATEDPERCENTYIELD", "...
null
null
18
HOUR
To a solution of (2S,4R)-N-{1-[4-(3-Amino-propoxy)-benzoyl]-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl}-N-(4-chloro-phenyl)-acetamide (50 mg, 0.10 mmol) in DCM (1 mL) was added trimethylsilyl isocyanate (23 mg, 0.20 mmol). The reaction mixture was stirred at room temperature for 18 hours. The reaction was quenched by ad...
10.6084/m9.figshare.5104873.v1
null
Primary amine.Silyl protective group
Urea
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
Other
C(Cl)Cl
null
18
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN)cc2)c2ccccc21.C[Si](C)(C)N=C=O>C(Cl)Cl>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCNC(N)=O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c6a1481f2eb64ff7bb5c602b6786876e
BrCCn1ccnc1.CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCn3ccnc3)cc2)c2ccccc21
ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)O)=O)C.C(=O)([O-])[O-].[K+].[K+].BrCCN1C=NC=C1>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCCN1C=NC=C1)=O)C
Br[CH2:24][CH2:25][n:26]1[cH:27][cH:28][n:29][cH:30]1.[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]([OH:23])[cH:31][cH:32]2)[c:33]2[cH:34][cH:35][cH:36][cH:37][c:38]21>>[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6]...
BrCCn1ccnc1.CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCn3ccnc3)cc2)c2ccccc21
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
O=C(c1ccc(OCCn2ccnc2)cc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Br-[CH2;D2;+0:1]-[C:2]-[#7;a:3].[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[#7;a:3]-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]
76
[{"value": 76.0, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCCN1C=NC=C1)=O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 75.6, "product": "ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCCN1C=NC=C1)=O)C", "details": "CALCULATEDPERCENTYIELD",...
80
CELSIUS
null
null
(2S,4R)-N-(4-Chloro-phenyl)-N-[1-(4-hydroxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide (0.065 g, 0.15 mmol) was dissolved in DMF at room temperature and K2CO3 (0.12 g, 0.87 mmol) was added. 1-(2-Bromo-ethyl)-1H-imidazole (0.08 g, 0.45 mmol) was added and the reaction was allowed to heat to 80° C. ove...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccccc1.c1c[nH]cn1.c1ccc2c(c1)CCC[NH]2
HBr
CN(C)C=O
80
null
BrCCn1ccnc1.CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21>CN(C)C=O>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCn3ccnc3)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a42dd5c064554bc2866a792dbe662f81
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.COC(=O)C(C)(C)CCBr>>COC(=O)C(C)(C)CCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)O)=O)C.C(=O)([O-])[O-].[K+].[K+].COC(C(CCBr)(C)C)=O>>COC(C(CCOC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C)(C)C)=O
[OH:10][c:11]1[cH:12][cH:13][c:14]([C:15](=[O:16])[N:17]2[c:18]3[cH:19][cH:20][cH:21][cH:22][c:23]3[C@H:24]([N:25]([C:26]([CH3:27])=[O:28])[c:29]3[cH:30][cH:31][c:32]([Cl:33])[cH:34][cH:35]3)[CH2:36][C@@H:37]2[CH3:38])[cH:39][cH:40]1.Br[CH2:9][CH2:8][C:5]([C:3]([O:2][CH3:1])=[O:4])([CH3:6])[CH3:7]>>[CH3:1][O:2][C:3](=[...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.COC(=O)C(C)(C)CCBr
COC(=O)C(C)(C)CCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Br-[CH2;D2;+0:1]-[C:2]-[C:3]-[C:4](-[#8:5])=[O;D1;H0:6].[OH;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[#8:5]-[C:4](=[O;D1;H0:6])-[C:3]-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:7]-[c:8](:[c:9]):[c:10]
77
[{"value": 77.0, "product": "COC(C(CCOC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C)(C)C)=O", "details": "PERCENTYIELD", "is_desired": false}]
80
CELSIUS
null
null
(2S,4R)-N-(4-Chloro-phenyl)-N-[1-(4-hydroxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide (0.126 g, 0.242 mmol) was dissolved in 3 ml DMF at room temperature and K2CO3 (0.267 g, 1.94 mmol) was added. 4-Bromo-2,2-dimethyl-butyric acid methyl ester (0.202 g, 0.969 mmol, prepared according to the procedure...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HBr
CN(C)C=O
80
null
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21.COC(=O)C(C)(C)CCBr>CN(C)C=O>COC(=O)C(C)(C)CCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-bb0a0e7b03734479b72b3075e9fd152a
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N3CCCC(C(=O)O)C3)cc2)c2ccccc21.[NH4+]>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N3CCCC(C(N)=O)C3)cc2)c2ccccc21
[Cl-].[NH4+].C=1C=CC2=C(C1)N=NN2O.CN(C)C(=[N+](C)C)ON1C2=C(C=CC=N2)N=N1.F[P-](F)(F)(F)(F)F.C(C)(C)N(CC)C(C)C.C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)N1CC(CCC1)C(=O)O)C)C1=CC=C(C=C1)Cl>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(C=C1)N1CC(CCC1)C(=O)N)C)C1=CC=C(C=C1)Cl
O[C:28]([CH:27]1[CH2:26][CH2:25][CH2:24][N:23]([c:22]2[cH:21][cH:20][c:19]([C:17]([N:16]3[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]4[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]4)[c:39]4[c:34]3[cH:35][cH:36][cH:37][cH:38]4)=[O:18])[cH:33][cH:32]2)[CH2:31]1)=[O:30].[NH4+:29]>>[CH3:1][C:2](=[O:3])[N:...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N3CCCC(C(=O)O)C3)cc2)c2ccccc21.[NH4+]
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N3CCCC(C(N)=O)C3)cc2)c2ccccc21
null
null
CN(C)C=O.C(C)(=O)OCC
Acylation
Carboxylic acid to amide conversion
1283aef55d7ee699f097a8e5267689198c76ba671644401547f902657820236d
cb0a71c3fb37a76e96fbd81aae6f95a28398a03d1ad2c8e877085e735efb98f1
O=C(c1ccc(N2CCCCC2)cc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])-[C:5]-[#7:6].[NH4+;D0:7]>>[#7:6]-[C:5]-[C:3](-[C;H0;D3;+0:1](-[NH2;D1;+0:7])=[O;D1;H0:2])-[C:4]
null
[]
null
null
16
HOUR
(2S,4R)-1-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenyl)-piperidine-3-carboxylic acid amide was prepared from (2S,4R)-1-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenyl)-piperidine-3-carboxylic acid. The acid (0.2 g, 0.366 mmol) wa...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
Primary amide
null
null
c1ccccc1.c1ccccc1.C1CC[NH]CC1.c1ccc2c(c1)CCC[NH]2
HO-
CN(C)C=O.C(C)(=O)OCC
null
16
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N3CCCC(C(=O)O)C3)cc2)c2ccccc21.[NH4+]>CN(C)C=O.C(C)(=O)OCC>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N3CCCC(C(N)=O)C3)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-fa551e689318482c890d0cab8c473395
CC(=O)Cl.CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCC3CCNCC3)cc2)c2ccccc21>>CC(=O)N1CCC(COc2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc2)CC1
ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCC1CCNCC1)=O)C.CCN(C(C)C)C(C)C.C(C)(=O)Cl>>C(C)(=O)N1CCC(CC1)COC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=C(C=C2)Cl)C)C=C1
Cl[C:2]([CH3:1])=[O:3].[NH:4]1[CH2:5][CH2:6][CH:7]([CH2:8][O:9][c:10]2[cH:11][cH:12][c:13]([C:14](=[O:15])[N:16]3[c:17]4[cH:18][cH:19][cH:20][cH:21][c:22]4[C@H:23]([N:24]([C:25]([CH3:26])=[O:27])[c:28]4[cH:29][cH:30][c:31]([Cl:32])[cH:33][cH:34]4)[CH2:35][C@@H:36]3[CH3:37])[cH:38][cH:39]2)[CH2:40][CH2:41]1>>[CH3:1][C:2...
CC(=O)Cl.CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCC3CCNCC3)cc2)c2ccccc21
CC(=O)N1CCC(COc2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc2)CC1
null
null
ClCCl
Acylation
N-alkylation of secondary amines with alkyl halides
aaa7c80569e6aa145ac8d7318e06893ee71aff0c965e85eca836522c948938d5
96cb0a2fed10552c5770a45a2d6523b47ac3e38928b4a9c698d8577451182dcd
O=C(c1ccc(OCC2CCNCC2)cc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Cl-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[C:4]-[C:5]-[NH;D2;+0:6]-[C:7]-[C:8]>>[C:4]-[C:5]-[N;H0;D3;+0:6](-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3])-[C:7]-[C:8]
61
[{"value": 49.0, "product": "C(C)(=O)N1CCC(CC1)COC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=C(C=C2)Cl)C)C=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 61.0, "product": "C(C)(=O)N1CCC(CC1)COC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=C(C=C2)Cl)C)C=C1", "details": "CALCULATEDPE...
null
null
8
HOUR
(2S,4R)-N-(4-Chloro-phenyl)-N-{2-methyl-1-[4-(piperidin-4-ylmethoxy)-benzoyl]-1,2,3,4-tetrahydro-quinolin-4-yl}-acetamide (0.075 g, 0.14 mmol) was dissolved in dichloromethane at room temperature. DIEA (0.1 mL, 0.56 mmol) and acetyl chloride (0.2 mL, 2.8 mmol) was added. The reaction was stirred at room temperature ove...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Secondary amine
Tertiary amide
C1CCNCC1
C1CC[NH]CC1
C1CC[NH]CC1.c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HCl
ClCCl
null
8
CC(=O)Cl.CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCC3CCNCC3)cc2)c2ccccc21>ClCCl>CC(=O)N1CCC(COc2ccc(C(=O)N3c4ccccc4[C@H](N(C(C)=O)c4ccc(Cl)cc4)C[C@@H]3C)cc2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f01ab17bfb7c4adebc2abb8cb0da1863
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN)cc2)c2ccccc21.CCOC(=O)CBr>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCNCC(=O)O)cc2)c2ccccc21
NCCCOC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=C(C=C2)Cl)C)C=C1.NCCCOC1=CC=C(C(=O)N2[C@H](C[C@H](C3=CC=CC=C23)N(C(C)=O)C2=CC=C(C=C2)Cl)C)C=C1.BrCC(=O)OCC.C([O-])([O-])=O.[K+].[K+]>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCCCNCC(=O)O)C=C1)C)C1=CC=C(C=C1)Cl
[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]([O:23][CH2:24][CH2:25][CH2:26][NH2:27])[cH:32][cH:33]2)[c:34]2[cH:35][cH:36][cH:37][cH:38][c:39]21.CC[O:31][C:29]([CH2:28]Br)=[O:30]>>[CH3:1][C:2](=[O:3])[N:4]([...
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN)cc2)c2ccccc21.CCOC(=O)CBr
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCNCC(=O)O)cc2)c2ccccc21
null
null
CN(C=O)C
Heteroatom Alkylation and Arylation
OtherReaction
92415cd0d503587dbc9232020ecee975743c4b5ccf369938adbe25f985d01623
3a5c5926d99d81cbe840ec25b6cb76f2e082bfbc6b5b9f02c592b9a82d36478b
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[O;H0;D2;+0:4]-C-C.[C:5]-[C:6]-[NH2;D1;+0:7]>>[C:5]-[C:6]-[NH;D2;+0:7]-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:4]
null
[]
50
CELSIUS
null
null
{[3-(4-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}phenoxy)propyl]amino}acetic acid was prepared from (2S,4R)-N-{1-[4-(3-amino-propoxy)-benzoyl]-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl}-N-(4-chloro-phenyl)-acetamide. (2S,4R)-N-{1-[4-(3-amino-propoxy)-benzoyl]-2-methyl-1,2,...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Primary amine
Carboxylic acid.Secondary amine
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
HBr
CN(C=O)C
50
null
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCN)cc2)c2ccccc21.CCOC(=O)CBr>CN(C=O)C>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCNCC(=O)O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7dc1f59994ee47179349fa16d76ae94a
CCOC(=O)CNCCCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCNCC(=O)O)cc2)c2ccccc21
C(C)OC(CNCCCOC1=CC=C(C=C1)C(=O)N1[C@H](C[C@H](C2=CC=CC=C12)N(C1=CC=C(C=C1)Cl)C(C)=O)C)=O.C(C)O.[OH-].[Na+]>>C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCCCNCC(=O)O)C=C1)C)C1=CC=C(C=C1)Cl
CC[O:31][C:29]([CH2:28][NH:27][CH2:26][CH2:25][CH2:24][O:23][c:22]1[cH:21][cH:20][c:19]([C:17]([N:16]2[C@@H:14]([CH3:15])[CH2:13][C@@H:12]([N:4]([C:2]([CH3:1])=[O:3])[c:5]3[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]3)[c:39]3[c:34]2[cH:35][cH:36][cH:37][cH:38]3)=[O:18])[cH:33][cH:32]1)=[O:30]>>[CH3:1][C:2](=[O:3])[N:4]([c:5...
CCOC(=O)CNCCCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCNCC(=O)O)cc2)c2ccccc21
null
null
O1CCCC1
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(c1ccccc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
C-C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
60
[{"value": 60.0, "product": "C(C)(=O)N([C@@H]1C[C@@H](N(C2=CC=CC=C12)C(=O)C1=CC=C(OCCCNCC(=O)O)C=C1)C)C1=CC=C(C=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
{[3-(4-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}phenoxy)propyl]amino}acetic ethyl ester was hydrolyzed to the acid by dissolving in tetrahydrofuran and ethanol and sodium hydroxide (1N) was added. The mixture was stirred at room temperature overnight. The mixture was cool...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)CCC[NH]2
Other
O1CCCC1
null
8
CCOC(=O)CNCCCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1>O1CCCC1>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCNCC(=O)O)cc2)c2ccccc21
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3456898986f84a9da8fecfc1c8aecc03
BrCCCn1cccn1.CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21>>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCn3cccn3)cc2)c2ccccc21
BrCCCN1N=CC=C1.BrCCCBr.N1N=CC=C1.[H-].[Na+].C(=O)([O-])[O-].[K+].[K+].ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)O)=O)C>>ClC1=CC=C(C=C1)N(C(C)=O)[C@@H]1C[C@@H](N(C2=CC=CC=C12)C(C1=CC=C(C=C1)OCCCN1N=CC=C1)=O)C
Br[CH2:24][CH2:25][CH2:26][n:27]1[cH:28][cH:29][cH:30][n:31]1.[CH3:1][C:2](=[O:3])[N:4]([c:5]1[cH:6][cH:7][c:8]([Cl:9])[cH:10][cH:11]1)[C@@H:12]1[CH2:13][C@H:14]([CH3:15])[N:16]([C:17](=[O:18])[c:19]2[cH:20][cH:21][c:22]([OH:23])[cH:32][cH:33]2)[c:34]2[cH:35][cH:36][cH:37][cH:38][c:39]21>>[CH3:1][C:2](=[O:3])[N:4]([c:5...
BrCCCn1cccn1.CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21
CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCn3cccn3)cc2)c2ccccc21
null
null
O1CCCC1.CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
O=C(c1ccc(OCCCn2cccn2)cc1)N1CC[C@@H](Nc2ccccc2)c2ccccc21
Br-[CH2;D2;+0:1]-[C:2]-[C:3].[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[C:3]-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]
null
[]
70
CELSIUS
3
HOUR
(2S,4R)-N-(4-Chloro-phenyl)-N-[1-(4-hydroxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide (75 mg, 0.17 mmol) was dissolved in DMF (1 mL) at room temperature. K2CO3 (47 mg, 0.34 mmol) was added followed by 1-(3-bromopropyl)-pyrazole (64 mg, 0.34 mmol) (prepared from the reaction of 1,3-dibromopropane and...
10.6084/m9.figshare.5104873.v1
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Primary halide.Aromatic alcohol
Ether
null
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c1ccccc1.c1ccccc1.c1cn[nH]c1.c1ccc2c(c1)CCC[NH]2
HBr
O1CCCC1.CN(C)C=O
70
3
BrCCCn1cccn1.CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(O)cc2)c2ccccc21>O1CCCC1.CN(C)C=O>CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OCCCn3cccn3)cc2)c2ccccc21