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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
product_smiles
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-0387783899c642a8b7eb4ba379bcdf5d
ord-d3dfcab9abe244c0b588d9f74b10f0ea
CN1CCCC(COc2ccc(N)cc2)C1.O=C1Nc2ccccc2C1=CO>>CN1CCCC(COc2ccc(NC=C3C(=O)Nc4ccccc43)cc2)C1
CN1CC(CCC1)COC1=CC=C(C=C1)N.OC=C1C(NC2=CC=CC=C12)=O>>CN1CC(CCC1)COC1=CC=C(C=C1)NC=C1C(NC2=CC=CC=C12)=O
[CH3:1][N:2]1[CH2:3][CH2:4][CH2:5][CH:6]([CH2:7][O:8][c:9]2[cH:10][cH:11][c:12]([NH2:13])[cH:25][cH:26]2)[CH2:27]1.O[CH:14]=[C:15]1[C:16](=[O:17])[NH:18][c:19]2[cH:20][cH:21][cH:22][cH:23][c:24]21>>[CH3:1][N:2]1[CH2:3][CH2:4][CH2:5][CH:6]([CH2:7][O:8][c:9]2[cH:10][cH:11][c:12]([NH:13][CH:14]=[C:15]3[C:16](=[O:17])[NH:1...
CN1CCCC(COc2ccc(N)cc2)C1.O=C1Nc2ccccc2C1=CO
CN1CCCC(COc2ccc(NC=C3C(=O)Nc4ccccc43)cc2)C1
null
null
null
Heteroatom Alkylation and Arylation
Reductive amination with alcohol
ac661a5987df49e763a2386679221354b73376953f4071e32e52e2d7e8877593
dc27e5e3871ba014ddcdbe66aa8244518b94cc851f1ff4159b6674656bc3b780
O=C1Nc2ccccc2C1=CNc1ccc(OCC2CCCNC2)cc1
O-[CH;D2;+0:1]=[C:2]1-[c:3]:[c:4]-[#7:5]-[C:6]-1=[O;D1;H0:7].[NH2;D1;+0:8]-[c:9](:[c:10]):[c:11]>>[O;D1;H0:7]=[C:6]1-[#7:5]-[c:4]:[c:3]-[C:2]-1=[CH;D2;+0:1]-[NH;D2;+0:8]-[c:9](:[c:10]):[c:11]
81.2
[{"value": 81.0, "product": "CN1CC(CCC1)COC1=CC=C(C=C1)NC=C1C(NC2=CC=CC=C12)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 81.2, "product": "CN1CC(CCC1)COC1=CC=C(C=C1)NC=C1C(NC2=CC=CC=C12)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
In a manner similar to that described in Example 231, 4-(1-methyl-piperidin-3-ylmethoxy)-phenylamine (656 mg, 1.2 equiv.) and 3-hydroxymethylene-1,3-dihydro-indol-2-one (400 mg, 2.48 mmol, 1 equiv.) are reacted to give the named compound as a yellow solid (732 mg, 81%). Conditions: See reaction.notes.procedure_details....
10.6084/m9.figshare.5104873.v1
null
Enol.Primary amine
Enamine
null
null
C1CC[NH]CC1.c1ccccc1.c1ccc2c(c1)CCN2
HO-
null
null
null
CN1CCCC(COc2ccc(N)cc2)C1.O=C1Nc2ccccc2C1=CO>>CN1CCCC(COc2ccc(NC=C3C(=O)Nc4ccccc43)cc2)C1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-2b854c689cfc4eab8446db253b93ae8f
CN1CCCC(COc2ccc(N)cc2)C1.O=C1Nc2cccc(F)c2C1=CO>>CN1CCCC(COc2ccc(NC=C3C(=O)Nc4cccc(F)c43)cc2)C1
CN1CC(CCC1)COC1=CC=C(C=C1)N.FC1=C2C(C(NC2=CC=C1)=O)=CO>>FC1=C2C(C(NC2=CC=C1)=O)=CNC1=CC=C(C=C1)OCC1CN(CCC1)C
[CH3:1][N:2]1[CH2:3][CH2:4][CH2:5][CH:6]([CH2:7][O:8][c:9]2[cH:10][cH:11][c:12]([NH2:13])[cH:26][cH:27]2)[CH2:28]1.O[CH:14]=[C:15]1[C:16](=[O:17])[NH:18][c:19]2[cH:20][cH:21][cH:22][c:23]([F:24])[c:25]21>>[CH3:1][N:2]1[CH2:3][CH2:4][CH2:5][CH:6]([CH2:7][O:8][c:9]2[cH:10][cH:11][c:12]([NH:13][CH:14]=[C:15]3[C:16](=[O:17...
CN1CCCC(COc2ccc(N)cc2)C1.O=C1Nc2cccc(F)c2C1=CO
CN1CCCC(COc2ccc(NC=C3C(=O)Nc4cccc(F)c43)cc2)C1
null
null
null
Heteroatom Alkylation and Arylation
Reductive amination with alcohol
ac661a5987df49e763a2386679221354b73376953f4071e32e52e2d7e8877593
dc27e5e3871ba014ddcdbe66aa8244518b94cc851f1ff4159b6674656bc3b780
O=C1Nc2ccccc2C1=CNc1ccc(OCC2CCCNC2)cc1
O-[CH;D2;+0:1]=[C:2]1-[c:3]:[c:4]-[#7:5]-[C:6]-1=[O;D1;H0:7].[NH2;D1;+0:8]-[c:9](:[c:10]):[c:11]>>[O;D1;H0:7]=[C:6]1-[#7:5]-[c:4]:[c:3]-[C:2]-1=[CH;D2;+0:1]-[NH;D2;+0:8]-[c:9](:[c:10]):[c:11]
68
[{"value": 68.0, "product": "FC1=C2C(C(NC2=CC=C1)=O)=CNC1=CC=C(C=C1)OCC1CN(CCC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 67.7, "product": "FC1=C2C(C(NC2=CC=C1)=O)=CNC1=CC=C(C=C1)OCC1CN(CCC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
In a manner similar to that described in Example 231, 4-(1-methyl-piperidin-3-ylmethoxy)-phenylamine (590 mg, 1.2 equiv.) and 4-fluoro-3-hydroxymethylene-1,3-dihydro-indol-2-one (400 mg, 2.23 mmol, 1 equiv.) are reacted to give the named compound as a yellow solid (576 mg, 68%). Conditions: See reaction.notes.procedure...
10.6084/m9.figshare.5104873.v1
null
Enol.Primary amine
Enamine
null
null
C1CC[NH]CC1.c1ccccc1.c1ccc2c(c1)CCN2
HO-
null
null
null
CN1CCCC(COc2ccc(N)cc2)C1.O=C1Nc2cccc(F)c2C1=CO>>CN1CCCC(COc2ccc(NC=C3C(=O)Nc4cccc(F)c43)cc2)C1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-2f938834d6b24fafa5b503cac5b7493d
CN1CCCC(COc2ccc(N)cc2)C1.O=C1Nc2ccc(F)cc2C1=CO>>CN1CCCC(COc2ccc(NC=C3C(=O)Nc4ccc(F)cc43)cc2)C1
Cl.CN1CC(CCC1)COC1=CC=C(C=C1)N.FC=1C=C2C(C(NC2=CC1)=O)=CO.CCN(CC)CC>>FC=1C=C2C(C(NC2=CC1)=O)=CNC1=CC=C(C=C1)OCC1CN(CCC1)C
[CH3:1][N:2]1[CH2:3][CH2:4][CH2:5][CH:6]([CH2:7][O:8][c:9]2[cH:10][cH:11][c:12]([NH2:13])[cH:26][cH:27]2)[CH2:28]1.O[CH:14]=[C:15]1[C:16](=[O:17])[NH:18][c:19]2[cH:20][cH:21][c:22]([F:23])[cH:24][c:25]21>>[CH3:1][N:2]1[CH2:3][CH2:4][CH2:5][CH:6]([CH2:7][O:8][c:9]2[cH:10][cH:11][c:12]([NH:13][CH:14]=[C:15]3[C:16](=[O:17...
CN1CCCC(COc2ccc(N)cc2)C1.O=C1Nc2ccc(F)cc2C1=CO
CN1CCCC(COc2ccc(NC=C3C(=O)Nc4ccc(F)cc43)cc2)C1
null
null
null
Heteroatom Alkylation and Arylation
Reductive amination with alcohol
ac661a5987df49e763a2386679221354b73376953f4071e32e52e2d7e8877593
dc27e5e3871ba014ddcdbe66aa8244518b94cc851f1ff4159b6674656bc3b780
O=C1Nc2ccccc2C1=CNc1ccc(OCC2CCCNC2)cc1
O-[CH;D2;+0:1]=[C:2]1-[c:3]:[c:4]-[#7:5]-[C:6]-1=[O;D1;H0:7].[NH2;D1;+0:8]-[c:9](:[c:10]):[c:11]>>[O;D1;H0:7]=[C:6]1-[#7:5]-[c:4]:[c:3]-[C:2]-1=[CH;D2;+0:1]-[NH;D2;+0:8]-[c:9](:[c:10]):[c:11]
77.2
[{"value": 77.0, "product": "FC=1C=C2C(C(NC2=CC1)=O)=CNC1=CC=C(C=C1)OCC1CN(CCC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 77.2, "product": "FC=1C=C2C(C(NC2=CC1)=O)=CNC1=CC=C(C=C1)OCC1CN(CCC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
In a manner similar to that described in Example 231, 4-(1-methyl-piperidin-3-ylmethoxy)-phenylamine hydrochloride (688 mg, 1.2 equiv.) and 5-fluoro-3-hydroxymethylene-1,3-dihydro-indol-2-one (400 mg, 2.23 mmol, 1 equiv.) with the addition of anhydrous Et3N (2.25 equiv.) are reacted to give the named compound as a yell...
10.6084/m9.figshare.5104873.v1
null
Enol.Primary amine
Enamine
null
null
C1CC[NH]CC1.c1ccccc1.c1ccc2c(c1)CCN2
HO-
null
null
null
CN1CCCC(COc2ccc(N)cc2)C1.O=C1Nc2ccc(F)cc2C1=CO>>CN1CCCC(COc2ccc(NC=C3C(=O)Nc4ccc(F)cc43)cc2)C1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-8edf77683bd44a118525e22bcc9d8585
CN1CCCC(COc2ccc(N)cc2)C1.O=C1Nc2ccc(Cl)cc2C1=CO>>CN1CCCC(COc2ccc(NC=C3C(=O)Nc4ccc(Cl)cc43)cc2)C1
Cl.CN1CC(CCC1)COC1=CC=C(C=C1)N.ClC=1C=C2C(C(NC2=CC1)=O)=CO.CCN(CC)CC>>ClC=1C=C2C(C(NC2=CC1)=O)=CNC1=CC=C(C=C1)OCC1CN(CCC1)C
[CH3:1][N:2]1[CH2:3][CH2:4][CH2:5][CH:6]([CH2:7][O:8][c:9]2[cH:10][cH:11][c:12]([NH2:13])[cH:26][cH:27]2)[CH2:28]1.O[CH:14]=[C:15]1[C:16](=[O:17])[NH:18][c:19]2[cH:20][cH:21][c:22]([Cl:23])[cH:24][c:25]21>>[CH3:1][N:2]1[CH2:3][CH2:4][CH2:5][CH:6]([CH2:7][O:8][c:9]2[cH:10][cH:11][c:12]([NH:13][CH:14]=[C:15]3[C:16](=[O:1...
CN1CCCC(COc2ccc(N)cc2)C1.O=C1Nc2ccc(Cl)cc2C1=CO
CN1CCCC(COc2ccc(NC=C3C(=O)Nc4ccc(Cl)cc43)cc2)C1
null
null
null
Heteroatom Alkylation and Arylation
Reductive amination with alcohol
ac661a5987df49e763a2386679221354b73376953f4071e32e52e2d7e8877593
dc27e5e3871ba014ddcdbe66aa8244518b94cc851f1ff4159b6674656bc3b780
O=C1Nc2ccccc2C1=CNc1ccc(OCC2CCCNC2)cc1
O-[CH;D2;+0:1]=[C:2]1-[c:3]:[c:4]-[#7:5]-[C:6]-1=[O;D1;H0:7].[NH2;D1;+0:8]-[c:9](:[c:10]):[c:11]>>[O;D1;H0:7]=[C:6]1-[#7:5]-[c:4]:[c:3]-[C:2]-1=[CH;D2;+0:1]-[NH;D2;+0:8]-[c:9](:[c:10]):[c:11]
49.3
[{"value": 49.0, "product": "ClC=1C=C2C(C(NC2=CC1)=O)=CNC1=CC=C(C=C1)OCC1CN(CCC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 49.3, "product": "ClC=1C=C2C(C(NC2=CC1)=O)=CNC1=CC=C(C=C1)OCC1CN(CCC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
In a manner similar to that described in Example 231, 4-(1-methyl-piperidin-3-ylmethoxy)-phenylamine hydrochloride (158 mg, 1.2 equiv.) and 5-chloro-3-hydroxymethylene-1,3-dihydro-indol-2-one (100 mg, 0.51 mmol, 1 equiv.) with the addition of anhydrous Et3N (2.11 equiv.) are reacted to give the named compound as a yell...
10.6084/m9.figshare.5104873.v1
null
Enol.Primary amine
Enamine
null
null
C1CC[NH]CC1.c1ccccc1.c1ccc2c(c1)CCN2
HO-
null
null
null
CN1CCCC(COc2ccc(N)cc2)C1.O=C1Nc2ccc(Cl)cc2C1=CO>>CN1CCCC(COc2ccc(NC=C3C(=O)Nc4ccc(Cl)cc43)cc2)C1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-05ec8b81a6074b43aabbd230172ff7a9
C1CCNCC1.O=C(O)Cc1ccc([N+](=O)[O-])cc1>>O=C(Cc1ccc([N+](=O)[O-])cc1)N1CCCCC1
C([O-])(O)=O.[Na+].[N+](=O)([O-])C1=CC=C(C=C1)CC(=O)O.N1CCCCC1>>[N+](=O)([O-])C1=CC=C(C=C1)CC(=O)N1CCCCC1
[NH:13]1[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]1.O[C:2](=[O:1])[CH2:3][c:4]1[cH:5][cH:6][c:7]([N+:8](=[O:9])[O-:10])[cH:11][cH:12]1>>[O:1]=[C:2]([CH2:3][c:4]1[cH:5][cH:6][c:7]([N+:8](=[O:9])[O-:10])[cH:11][cH:12]1)[N:13]1[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]1
C1CCNCC1.O=C(O)Cc1ccc([N+](=O)[O-])cc1
O=C(Cc1ccc([N+](=O)[O-])cc1)N1CCCCC1
null
null
O1CCCC1
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
fbfce93ec1ece674255bb96c5cec09ad611382b41cf117dfe580015e21744a71
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
O=C(Cc1ccccc1)N1CCCCC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[c:4].[C:5]-[C:6]-[NH;D2;+0:7]-[C:8]-[C:9]>>[C:5]-[C:6]-[N;H0;D3;+0:7](-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[c:4])-[C:8]-[C:9]
null
[]
null
null
8
HOUR
A room temperature solution of 2.53 gms. (4-Nitro-phenyl)-acetic acid in tetrahydrofuran (10 mL) is treated with 2.44 gms. 1′,1′-carbonyl-diimidizole and immediately immersed in an ice bath. The reaction mixture is stirred in the ice bath for 30 minutes then it is allowed to warm to room temperature. Once at room tempe...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
C1CCNCC1
C1CC[NH]CC1
c1ccccc1.C1CC[NH]CC1
HO-
O1CCCC1
null
8
C1CCNCC1.O=C(O)Cc1ccc([N+](=O)[O-])cc1>O1CCCC1>O=C(Cc1ccc([N+](=O)[O-])cc1)N1CCCCC1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-330fa2a41eb648ecb7a397e4c790b955
O=[N+]([O-])c1ccc(CCN2CCCCC2)cc1>>Nc1ccc(CCN2CCCCC2)cc1
[OH-].[Na+].[N+](=O)([O-])C1=CC=C(C=C1)CCN1CCCCC1.C(C)(=O)O.Cl>>N1(CCCCC1)CCC1=CC=C(C=C1)N
O=[N+:1]([O-])[c:2]1[cH:3][cH:4][c:5]([CH2:6][CH2:7][N:8]2[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]2)[cH:14][cH:15]1>>[NH2:1][c:2]1[cH:3][cH:4][c:5]([CH2:6][CH2:7][N:8]2[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]2)[cH:14][cH:15]1
O=[N+]([O-])c1ccc(CCN2CCCCC2)cc1
Nc1ccc(CCN2CCCCC2)cc1
null
null
O
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccc(CCN2CCCCC2)cc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
58.4
[{"value": 58.4, "product": "N1(CCCCC1)CCC1=CC=C(C=C1)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
65
CELSIUS
null
null
1-[2-(4-Nitro-phenyl)-ethyl]-piperidine (0.1178 gms.) is suspended in 4.5 mL of a 1:1 (v:v) solution of acetic acid and water. The suspension is then immersed in a 65° C. oil bath and treated in dropwise fashion with 9 mL of an ˜10 wt. % solution of TiCl3 in 20–30 wt. % HCl. Over the course of the addition a color chan...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccccc1.C1CC[NH]CC1
Other
O
65
null
O=[N+]([O-])c1ccc(CCN2CCCCC2)cc1>O>Nc1ccc(CCN2CCCCC2)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-5e9e9595f9b24f91af653c3b48e4f759
Cc1cccc2c1CC(=O)N2.Nc1ccc(NCCCN2CCOCC2)cc1>>Cc1cccc2c1C(=CNc1ccc(NCCCN3CCOCC3)cc1)C(=O)N2
NC1=CC=CC=C1.CC1=C2CC(NC2=CC=C1)=O.N1C(CC2=CC=CC=C12)=O.N1(CCOCC1)CCCNC1=CC=C(C=C1)N>>CC1=C2C(C(NC2=CC=C1)=O)=CNC1=CC=C(C=C1)NCCCN1CCOCC1
[CH3:1][c:2]1[cH:3][cH:4][cH:5][c:6]2[c:7]1[CH2:8][C:27](=[O:28])[NH:29]2.[NH2:10][c:11]1[cH:12][cH:13][c:14]([NH:15][CH2:16][CH2:17][CH2:18][N:19]2[CH2:20][CH2:21][O:22][CH2:23][CH2:24]2)[cH:25][cH:26]1>>[CH3:1][c:2]1[cH:3][cH:4][cH:5][c:6]2[c:7]1[C:8](=[CH:9][NH:10][c:11]1[cH:12][cH:13][c:14]([NH:15][CH2:16][CH2:17][...
Cc1cccc2c1CC(=O)N2.Nc1ccc(NCCCN2CCOCC2)cc1
Cc1cccc2c1C(=CNc1ccc(NCCCN3CCOCC3)cc1)C(=O)N2
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
f758903f83045820aa2796f0613e9efc40596c9df4963f018a1708e6363b1ea6
7cfdda6b313596a2c22c8b14542e800c357c71515516e6891ac9e4b2afd7445f
O=C1Nc2ccccc2C1=CNc1ccc(NCCCN2CCOCC2)cc1
[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4].[O;D1;H0:5]=[C:6]1-[#7:7]-[c:8]:[c:9](:[c:10])-[CH2;D2;+0:11]-1>>[O;D1;H0:5]=[C:6]1-[#7:7]-[c:8]:[c:9](:[c:10])-[C;H0;D3;+0:11]-1=[C:12]-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
null
null
null
null
The named compound is prepared by substituting 4-methyl-1,3-dihydro-indol-2-one for the 1,3-dihydro-indol-2-one and N-(3-morpholin-4-yl-propyl)-benzene-1,4-diamine (used for the preparation of Example 290) for aniline in the reaction of Example 1. Conditions: See reaction.notes.procedure_details. Workup: The named comp...
10.6084/m9.figshare.5104873.v1
null
Primary amine
Enamine
c1ccc2c(c1)CCN2
c1ccc2c(c1)CCN2
c1ccccc1.C1COCC[NH]1.c1ccc2c(c1)CCN2
Other
null
null
null
Cc1cccc2c1CC(=O)N2.Nc1ccc(NCCCN2CCOCC2)cc1>>Cc1cccc2c1C(=CNc1ccc(NCCCN3CCOCC3)cc1)C(=O)N2
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-b5e621a7e85043d59505c128388c60b9
O=[N+]([O-])c1ccc(NCCCN2CCOCC2)cc1>>Nc1ccc(NCCCN2CCOCC2)cc1
N1(CCOCC1)CCCNC1=CC=C(C=C1)[N+](=O)[O-].O.NN>>N1(CCOCC1)CCCNC1=CC=C(C=C1)N
O=[N+:1]([O-])[c:2]1[cH:3][cH:4][c:5]([NH:6][CH2:7][CH2:8][CH2:9][N:10]2[CH2:11][CH2:12][O:13][CH2:14][CH2:15]2)[cH:16][cH:17]1>>[NH2:1][c:2]1[cH:3][cH:4][c:5]([NH:6][CH2:7][CH2:8][CH2:9][N:10]2[CH2:11][CH2:12][O:13][CH2:14][CH2:15]2)[cH:16][cH:17]1
O=[N+]([O-])c1ccc(NCCCN2CCOCC2)cc1
Nc1ccc(NCCCN2CCOCC2)cc1
null
[Ni].[Ni].[Ni]
O.C(C)O
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccc(NCCCN2CCOCC2)cc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
50
CELSIUS
null
null
A suspension of 5.00 gms. of (3-morpholin-4-yl-propyl)-(4-nitro-phenyl)-amine in 110 mL of ethanol is heated to 50° C. Once dissolution is achieved 5.49 mL hydrazine monohydrate is added to the solution. A Raney nickel slurry in water is added to the 50° C. solution dropwise, waiting after each addition for the bubblin...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccccc1.C1COCC[NH]1
Other
[Ni].[Ni].[Ni].O.C(C)O
50
null
O=[N+]([O-])c1ccc(NCCCN2CCOCC2)cc1>[Ni].[Ni].[Ni].O.C(C)O>Nc1ccc(NCCCN2CCOCC2)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-ade4ba1e0e814d698861e81744a019a2
Nc1ccc(NCCCN2CCOCC2)cc1.Nc1ccccc1.O=C1Cc2ccccc2N1>>O=C1Nc2ccccc2C1=CNc1ccc(NCCCN2CCOCC2)cc1
NC1=CC=CC=C1.N1C(CC2=CC=CC=C12)=O.N1(CCOCC1)CCCNC1=CC=C(C=C1)N>>N1(CCOCC1)CCCNC1=CC=C(C=C1)NC=C1C(NC2=CC=CC=C12)=O
[NH2:12][c:13]1[cH:14][cH:15][c:16]([NH:17][CH2:18][CH2:19][CH2:20][N:21]2[CH2:22][CH2:23][O:24][CH2:25][CH2:26]2)[cH:27][cH:28]1.Nc1cccc[cH:11]1.[O:1]=[C:2]1[NH:3][c:4]2[cH:5][cH:6][cH:7][cH:8][c:9]2[CH2:10]1>>[O:1]=[C:2]1[NH:3][c:4]2[cH:5][cH:6][cH:7][cH:8][c:9]2[C:10]1=[CH:11][NH:12][c:13]1[cH:14][cH:15][c:16]([NH:1...
Nc1ccc(NCCCN2CCOCC2)cc1.Nc1ccccc1.O=C1Cc2ccccc2N1
O=C1Nc2ccccc2C1=CNc1ccc(NCCCN2CCOCC2)cc1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
614736c6452b49792a9cfef0c47c1bbcfeb2e44995a7e43fa6798fd677ee6ad9
cb38d990d25d6ca3504b5351083a2f2348c4fe81dc23cc421367015ba77adfa5
O=C1Nc2ccccc2C1=CNc1ccc(NCCCN2CCOCC2)cc1
N-c1:[cH;D2;+0:1]:c:c:c:c:1.[NH2;D1;+0:2]-[c:3](:[c:4]):[c:5].[O;D1;H0:6]=[C:7]1-[#7:8]-[c:9]:[c:10](:[c:11])-[CH2;D2;+0:12]-1>>[O;D1;H0:6]=[C:7]1-[#7:8]-[c:9]:[c:10](:[c:11])-[C;H0;D3;+0:12]-1=[CH;D2;+0:1]-[NH;D2;+0:2]-[c:3](:[c:4]):[c:5]
null
[]
null
null
null
null
Example 298–301 are prepared by substituting the appropriate 6′-fluoro or 5′-chloro or 5′-fluoro or 4′-fluoro substituted 1,3-dihydro-indol-2-one for the 1,3-dihydro-indol-2-one and N-(3-morpholin-4-yl-propyl)-benzene-1,4-diamine (used in the preparation of Example 297) for aniline in the reaction of Example 1. Conditi...
10.6084/m9.figshare.5104873.v1
null
Primary amine.Primary amine
Enamine
c1ccccc1.c1ccc2c(c1)CCN2
c1ccc2c(c1)CCN2
c1ccc2c(c1)CCN2.c1ccccc1.C1COCC[NH]1
Other
null
null
null
Nc1ccc(NCCCN2CCOCC2)cc1.Nc1ccccc1.O=C1Cc2ccccc2N1>>O=C1Nc2ccccc2C1=CNc1ccc(NCCCN2CCOCC2)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-bd5c83c4a79a42c4a343217e1748191c
CN1CCN(CCCN)CC1.O=[N+]([O-])c1ccc(F)cc1>>CN1CCN(CCCNc2ccc([N+](=O)[O-])cc2)CC1
FC1=CC=C(C=C1)[N+](=O)[O-].CN1CCN(CC1)CCCN.C(C)(C)NC(C)C>>CN1CCN(CC1)CCCNC1=CC=C(C=C1)[N+](=O)[O-]
[CH3:1][N:2]1[CH2:3][CH2:4][N:5]([CH2:6][CH2:7][CH2:8][NH2:9])[CH2:19][CH2:20]1.F[c:10]1[cH:11][cH:12][c:13]([N+:14](=[O:15])[O-:16])[cH:17][cH:18]1>>[CH3:1][N:2]1[CH2:3][CH2:4][N:5]([CH2:6][CH2:7][CH2:8][NH:9][c:10]2[cH:11][cH:12][c:13]([N+:14](=[O:15])[O-:16])[cH:17][cH:18]2)[CH2:19][CH2:20]1
CN1CCN(CCCN)CC1.O=[N+]([O-])c1ccc(F)cc1
CN1CCN(CCCNc2ccc([N+](=O)[O-])cc2)CC1
null
null
O1CCOCC1
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(NCCCN2CCNCC2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C:6]-[C:7]-[NH2;D1;+0:8]>>[C:6]-[C:7]-[NH;D2;+0:8]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]
null
[]
null
null
null
null
A mixture of 4.44 mL of p-fluoronitrobenzene, 6 gms. 3-(4-methyl-piperazin-1-yl)-propylamine and 6.65 mL N,N-diisopropylamine in 19 mL dioxane is heated at 105° C. for 2 days. The reaction mixture is cooled to room temperature, evaporated to dryness, and recrystallized from hot isopropanol yielding [3-(4-methyl-piperaz...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
C1C[NH]CC[NH]1.c1ccccc1
HF
O1CCOCC1
null
null
CN1CCN(CCCN)CC1.O=[N+]([O-])c1ccc(F)cc1>O1CCOCC1>CN1CCN(CCCNc2ccc([N+](=O)[O-])cc2)CC1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-eb1ff254344f4230a9d813e4b5254294
CN1CCN(CCCNc2ccc([N+](=O)[O-])cc2)CC1>>CN1CCN(CCCNc2ccc(N)cc2)CC1
CN1CCN(CC1)CCCNC1=CC=C(C=C1)[N+](=O)[O-].O.NN>>CN1CCN(CC1)CCCNC1=CC=C(C=C1)N
O=[N+:14]([O-])[c:13]1[cH:12][cH:11][c:10]([NH:9][CH2:8][CH2:7][CH2:6][N:5]2[CH2:4][CH2:3][N:2]([CH3:1])[CH2:18][CH2:17]2)[cH:16][cH:15]1>>[CH3:1][N:2]1[CH2:3][CH2:4][N:5]([CH2:6][CH2:7][CH2:8][NH:9][c:10]2[cH:11][cH:12][c:13]([NH2:14])[cH:15][cH:16]2)[CH2:17][CH2:18]1
CN1CCN(CCCNc2ccc([N+](=O)[O-])cc2)CC1
CN1CCN(CCCNc2ccc(N)cc2)CC1
null
[Ni].[Ni].[Ni]
O.C(C)O
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccc(NCCCN2CCNCC2)cc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
50
CELSIUS
null
null
A suspension of 0.1385 gms. of [3-(4-methyl-piperazin-1-yl)-propyl]-(4-nitro-phenyl)-amine in 3 mL of ethanol is heated to 50° C. Once dissolution is achieved 0.144 mL hydrazine monohydrate is addded to the solution. A Raney nickel slurry in water is added to the 50° C. solution dropwise, waiting after each addition fo...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
C1C[NH]CC[NH]1.c1ccccc1
Other
[Ni].[Ni].[Ni].O.C(C)O
50
null
CN1CCN(CCCNc2ccc([N+](=O)[O-])cc2)CC1>[Ni].[Ni].[Ni].O.C(C)O>CN1CCN(CCCNc2ccc(N)cc2)CC1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-7c6fcb32e13c4d3a9d0af936d845a880
CN1CCN(CCCNc2ccc(N)cc2)CC1.Cc1cccc2c1CC(=O)N2>>Cc1cccc2c1C(=CNc1ccc(NCCCN3CCN(C)CC3)cc1)C(=O)N2
NC1=CC=CC=C1.CC1=C2CC(NC2=CC=C1)=O.N1C(CC2=CC=CC=C12)=O.CN1CCN(CC1)CCCNC1=CC=C(C=C1)N>>CC1=C2C(C(NC2=CC=C1)=O)=CNC1=CC=C(C=C1)NCCCN1CCN(CC1)C
[NH2:10][c:11]1[cH:12][cH:13][c:14]([NH:15][CH2:16][CH2:17][CH2:18][N:19]2[CH2:20][CH2:21][N:22]([CH3:23])[CH2:24][CH2:25]2)[cH:26][cH:27]1.[CH3:1][c:2]1[cH:3][cH:4][cH:5][c:6]2[c:7]1[CH2:8][C:28](=[O:29])[NH:30]2>>[CH3:1][c:2]1[cH:3][cH:4][cH:5][c:6]2[c:7]1[C:8](=[CH:9][NH:10][c:11]1[cH:12][cH:13][c:14]([NH:15][CH2:16...
CN1CCN(CCCNc2ccc(N)cc2)CC1.Cc1cccc2c1CC(=O)N2
Cc1cccc2c1C(=CNc1ccc(NCCCN3CCN(C)CC3)cc1)C(=O)N2
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
f758903f83045820aa2796f0613e9efc40596c9df4963f018a1708e6363b1ea6
7cfdda6b313596a2c22c8b14542e800c357c71515516e6891ac9e4b2afd7445f
O=C1Nc2ccccc2C1=CNc1ccc(NCCCN2CCNCC2)cc1
[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4].[O;D1;H0:5]=[C:6]1-[#7:7]-[c:8]:[c:9](:[c:10])-[CH2;D2;+0:11]-1>>[O;D1;H0:5]=[C:6]1-[#7:7]-[c:8]:[c:9](:[c:10])-[C;H0;D3;+0:11]-1=[C:12]-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
null
null
null
null
The named compound is prepared by substituting 4-methyl-1,3-dihydro-indol-2-one for the 1,3-dihydro-indol-2-one and N-[3-(4-methyl-piperazin-1-yl)-propyl]-benzene-1,4-diamine (used for the preparation of Example 302) for aniline in the reaction of Example 1. Conditions: See reaction.notes.procedure_details. Workup: The...
10.6084/m9.figshare.5104873.v1
null
Primary amine
Enamine
c1ccc2c(c1)CCN2
c1ccc2c(c1)CCN2
c1ccccc1.C1C[NH]CC[NH]1.c1ccc2c(c1)CCN2
Other
null
null
null
CN1CCN(CCCNc2ccc(N)cc2)CC1.Cc1cccc2c1CC(=O)N2>>Cc1cccc2c1C(=CNc1ccc(NCCCN3CCN(C)CC3)cc1)C(=O)N2
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-a0fe886e64964a629a4f35c8f12e3ce0
CN1CCN(CCCNc2ccc(N)cc2)CC1.O=C1Cc2ccc(F)cc2N1>>CN1CCN(CCCNc2ccc(NC=C3C(=O)Nc4cc(F)ccc43)cc2)CC1
NC1=CC=CC=C1.FC1=CC=C2CC(NC2=C1)=O.N1C(CC2=CC=CC=C12)=O.CN1CCN(CC1)CCCNC1=CC=C(C=C1)N>>FC1=CC=C2C(C(NC2=C1)=O)=CNC1=CC=C(C=C1)NCCCN1CCN(CC1)C
[CH3:1][N:2]1[CH2:3][CH2:4][N:5]([CH2:6][CH2:7][CH2:8][NH:9][c:10]2[cH:11][cH:12][c:13]([NH2:14])[cH:27][cH:28]2)[CH2:29][CH2:30]1.[CH2:16]1[C:17](=[O:18])[NH:19][c:20]2[cH:21][c:22]([F:23])[cH:24][cH:25][c:26]21>>[CH3:1][N:2]1[CH2:3][CH2:4][N:5]([CH2:6][CH2:7][CH2:8][NH:9][c:10]2[cH:11][cH:12][c:13]([NH:14][CH:15]=[C:...
CN1CCN(CCCNc2ccc(N)cc2)CC1.O=C1Cc2ccc(F)cc2N1
CN1CCN(CCCNc2ccc(NC=C3C(=O)Nc4cc(F)ccc43)cc2)CC1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
f758903f83045820aa2796f0613e9efc40596c9df4963f018a1708e6363b1ea6
7cfdda6b313596a2c22c8b14542e800c357c71515516e6891ac9e4b2afd7445f
O=C1Nc2ccccc2C1=CNc1ccc(NCCCN2CCNCC2)cc1
[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4].[O;D1;H0:5]=[C:6]1-[#7:7]-[c:8]:[c:9](:[c:10])-[CH2;D2;+0:11]-1>>[O;D1;H0:5]=[C:6]1-[#7:7]-[c:8]:[c:9](:[c:10])-[C;H0;D3;+0:11]-1=[C:12]-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
null
null
null
null
The named compound is prepared by substituting 6-fluoro-1,3-dihydro-indol-2-one for the 1,3-dihydro-indol-2-one and N-[3-(4-methyl-piperazin-1-yl)-propyl]-benzene-1,4-diamine (used for the preparation of Example 302) for aniline in the reaction of Example 1. Conditions: See reaction.notes.procedure_details. Workup: The...
10.6084/m9.figshare.5104873.v1
null
Primary amine
Enamine
c1ccc2c(c1)CCN2
c1ccc2c(c1)CCN2
C1C[NH]CC[NH]1.c1ccccc1.c1ccc2c(c1)CCN2
Other
null
null
null
CN1CCN(CCCNc2ccc(N)cc2)CC1.O=C1Cc2ccc(F)cc2N1>>CN1CCN(CCCNc2ccc(NC=C3C(=O)Nc4cc(F)ccc43)cc2)CC1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-c2c660de81c34d78b9d027c0b0d05515
FC1CCNC1.O=C1Nc2ccccc2C1=CNc1ccc(OCCCI)cc1>>O=C1Nc2ccccc2C1=CNc1ccc(OCCCN2CCC(F)C2)cc1
ICCCOC1=CC=C(C=C1)NC=C1C(NC2=CC=CC=C12)=O.Cl.FC1CNCC1>>FC1CN(CC1)CCCOC1=CC=C(C=C1)NC=C1C(NC2=CC=CC=C12)=O
[NH:21]1[CH2:22][CH2:23][CH:24]([F:25])[CH2:26]1.I[CH2:20][CH2:19][CH2:18][O:17][c:16]1[cH:15][cH:14][c:13]([NH:12][CH:11]=[C:10]2[C:2](=[O:1])[NH:3][c:4]3[cH:5][cH:6][cH:7][cH:8][c:9]32)[cH:28][cH:27]1>>[O:1]=[C:2]1[NH:3][c:4]2[cH:5][cH:6][cH:7][cH:8][c:9]2[C:10]1=[CH:11][NH:12][c:13]1[cH:14][cH:15][c:16]([O:17][CH2:1...
FC1CCNC1.O=C1Nc2ccccc2C1=CNc1ccc(OCCCI)cc1
O=C1Nc2ccccc2C1=CNc1ccc(OCCCN2CCC(F)C2)cc1
null
null
null
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
19b442dc26882f89f7423416f5e0a16bdb8e48776df57991434a0634e21f0505
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
O=C1Nc2ccccc2C1=CNc1ccc(OCCCN2CCCC2)cc1
I-[CH2;D2;+0:1]-[C:2]-[C:3].[C:4]1-[C:5]-[C:6]-[C:7]-[NH;D2;+0:8]-1>>[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:8]1-[C:4]-[C:5]-[C:6]-[C:7]-1
null
[]
null
null
null
null
In a manner similar to that described in Example 217, 3-{[4-(3-Iodo-propoxy)-phenylamino]-methylene}-1,3-dihydro-indol-2-one and 3-fluoro-pyrrolidine hydrochloride (226 mg, 1.2 equiv.) (prepared by the method of Giardina, G et al, Synlett (1995), (1), 55–7) are converted to the named compound as a slightly brownish yel...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CCNC1
C1CC[NH]C1
c1ccc2c(c1)CCN2.c1ccccc1.C1CC[NH]C1
HI
null
null
null
FC1CCNC1.O=C1Nc2ccccc2C1=CNc1ccc(OCCCI)cc1>>O=C1Nc2ccccc2C1=CNc1ccc(OCCCN2CCC(F)C2)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-f62c3c18b80740c0b6b9fd0839671267
C1COCCN1.O=C(O)Cc1ccc([N+](=O)[O-])cc1>>O=C(Cc1ccc([N+](=O)[O-])cc1)N1CCOCC1
[N+](=O)([O-])C1=CC=C(C=C1)CC(=O)O.N1CCOCC1.C([O-])(O)=O.[Na+]>>N1(CCOCC1)C(CC1=CC=C(C=C1)[N+](=O)[O-])=O
[NH:13]1[CH2:14][CH2:15][O:16][CH2:17][CH2:18]1.O[C:2](=[O:1])[CH2:3][c:4]1[cH:5][cH:6][c:7]([N+:8](=[O:9])[O-:10])[cH:11][cH:12]1>>[O:1]=[C:2]([CH2:3][c:4]1[cH:5][cH:6][c:7]([N+:8](=[O:9])[O-:10])[cH:11][cH:12]1)[N:13]1[CH2:14][CH2:15][O:16][CH2:17][CH2:18]1
C1COCCN1.O=C(O)Cc1ccc([N+](=O)[O-])cc1
O=C(Cc1ccc([N+](=O)[O-])cc1)N1CCOCC1
null
null
O1CCCC1
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
2ef483949e7ba3e5f888cf14cdce25fa611f75be09fdf1854a473be519821b59
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
O=C(Cc1ccccc1)N1CCOCC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[c:4].[#8:5]1-[C:6]-[C:7]-[NH;D2;+0:8]-[C:9]-[C:10]-1>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[C:3]-[c:4])-[N;H0;D3;+0:8]1-[C:7]-[C:6]-[#8:5]-[C:10]-[C:9]-1
null
[]
35
CELSIUS
1
HOUR
A room temperature solution of 1.8839 gms. (4-Nitro-phenyl)-acetic acid in tetrahydrofuran (5 mL) is treated with 1.8069 gms. 1′,1′-carbonyl-diimidizole. The reaction mixture is stirred for 1 h. The reaction mixture is then treated with 1.0 mL morpholine. The reaction is heated overnight at 35° C. The reaction is then ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
C1COCCN1
C1COCC[NH]1
c1ccccc1.C1COCC[NH]1
HO-
O1CCCC1
35
1
C1COCCN1.O=C(O)Cc1ccc([N+](=O)[O-])cc1>O1CCCC1>O=C(Cc1ccc([N+](=O)[O-])cc1)N1CCOCC1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-4a49e417045f44d7a0b79b55aee7f367
C1COCCN1.O=C(O)CCCc1ccc([N+](=O)[O-])cc1>>O=C(CCCc1ccc([N+](=O)[O-])cc1)N1CCOCC1
[N+](=O)([O-])C1=CC=C(C=C1)CCCC(=O)O.N1CCOCC1.C([O-])(O)=O.[Na+]>>N1(CCOCC1)C(CCCC1=CC=C(C=C1)[N+](=O)[O-])=O
[NH:15]1[CH2:16][CH2:17][O:18][CH2:19][CH2:20]1.O[C:2](=[O:1])[CH2:3][CH2:4][CH2:5][c:6]1[cH:7][cH:8][c:9]([N+:10](=[O:11])[O-:12])[cH:13][cH:14]1>>[O:1]=[C:2]([CH2:3][CH2:4][CH2:5][c:6]1[cH:7][cH:8][c:9]([N+:10](=[O:11])[O-:12])[cH:13][cH:14]1)[N:15]1[CH2:16][CH2:17][O:18][CH2:19][CH2:20]1
C1COCCN1.O=C(O)CCCc1ccc([N+](=O)[O-])cc1
O=C(CCCc1ccc([N+](=O)[O-])cc1)N1CCOCC1
null
null
O1CCCC1
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
2ef483949e7ba3e5f888cf14cdce25fa611f75be09fdf1854a473be519821b59
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
O=C(CCCc1ccccc1)N1CCOCC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[C:4].[#8:5]1-[C:6]-[C:7]-[NH;D2;+0:8]-[C:9]-[C:10]-1>>[C:4]-[C:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:8]1-[C:7]-[C:6]-[#8:5]-[C:10]-[C:9]-1
null
[]
35
CELSIUS
1
HOUR
A room temperature solution of 1.1180 gms. 4-(4-nitro-phenyl)-butyric acid in tetrahydrofuran (3 mL) is treated with 0.9052 gms. 1′,1′-carbonyl-diimidizole using an ice bath to attenuate the intensity of the reaction. The reaction mixture is stirred for 1 h. The reaction mixture is then treated with 0.5 mL morpholine. ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
C1COCCN1
C1COCC[NH]1
c1ccccc1.C1COCC[NH]1
HO-
O1CCCC1
35
1
C1COCCN1.O=C(O)CCCc1ccc([N+](=O)[O-])cc1>O1CCCC1>O=C(CCCc1ccc([N+](=O)[O-])cc1)N1CCOCC1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-f164a86a1ed0474fb9451ef746bcacbf
C1COCCN1.O=C(O)CCCc1ccc([N+](=O)[O-])cc1>>O=C(CCCc1ccc([N+](=O)[O-])cc1)N1CCCCC1
C([O-])(O)=O.[Na+].[N+](=O)([O-])C1=CC=C(C=C1)CCCC(=O)O.N1CCOCC1>>[N+](=O)([O-])C1=CC=C(C=C1)CCCC(=O)N1CCCCC1
O1[CH2:17][CH2:16][NH:15][CH2:20][CH2:19]1.O[C:2](=[O:1])[CH2:3][CH2:4][CH2:5][c:6]1[cH:7][cH:8][c:9]([N+:10](=[O:11])[O-:12])[cH:13][cH:14]1>>[O:1]=[C:2]([CH2:3][CH2:4][CH2:5][c:6]1[cH:7][cH:8][c:9]([N+:10](=[O:11])[O-:12])[cH:13][cH:14]1)[N:15]1[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]1
C1COCCN1.O=C(O)CCCc1ccc([N+](=O)[O-])cc1
O=C(CCCc1ccc([N+](=O)[O-])cc1)N1CCCCC1
null
null
O1CCCC1
Acylation
OtherReaction
a96d25d999a7e3c312b77c7e0e3a251b11b05f4e7f9892abbe6806618e604717
face37508b08df202202ccc41ac58b51abeb084067a6e34d8ef463ce96851537
O=C(CCCc1ccccc1)N1CCCCC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[C:4].O1-[CH2;D2;+0:5]-[C:6]-[NH;D2;+0:7]-[C:8]-[CH2;D2;+0:9]-1>>[C:4]-[C:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:7]1-[C:6]-[CH2;D2;+0:5]-[C:10]-[CH2;D2;+0:9]-[C:8]-1
null
[]
35
CELSIUS
null
null
A room temperature solution of 1.1220 gms. 4-(4-nitro-phenyl)-butyric acid in tetrahydrofuran (3 mL) is treated with 0.8978 gms. 1′,1′-carbonyl-diimidizole using an ice bath to attenuate the intensity of the reaction. The reaction mixture is stirred for 30 minutes in the ice bath and 30 minutes at room temperature. The...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Ether.Secondary amine
Tertiary amide
C1COCCN1
C1CC[NH]CC1
c1ccccc1.C1CC[NH]CC1
Other
O1CCCC1
35
null
C1COCCN1.O=C(O)CCCc1ccc([N+](=O)[O-])cc1>O1CCCC1>O=C(CCCc1ccc([N+](=O)[O-])cc1)N1CCCCC1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-0fe46712cd1942958efdafa5a636c66d
CC(C)(C)OC(=O)Nc1ccccc1N.N#Cc1ccc(C(=O)O)cn1>>CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(C#N)nc1
C(=O)(OC(C)(C)C)NC1=C(C=CC=C1)N.C(CC(O)(C(=O)O)CC(=O)O)(=O)O.C(#N)C1=NC=C(C(=O)O)C=C1.CN1CCOCC1.ClC(=O)OCC(C)C>>C(C)(C)(C)OC(NC1=C(C=CC=C1)NC(=O)C=1C=NC(=CC1)C#N)=O
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][c:9]1[cH:10][cH:11][cH:12][cH:13][c:14]1[NH2:15].O[C:16](=[O:17])[c:18]1[cH:19][cH:20][c:21]([C:22]#[N:23])[n:24][cH:25]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][c:9]1[cH:10][cH:11][cH:12][cH:13][c:14]1[NH:15][C:16](=[O:17])[c:18]1[cH:19][cH:20][c:2...
CC(C)(C)OC(=O)Nc1ccccc1N.N#Cc1ccc(C(=O)O)cn1
CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(C#N)nc1
null
null
CN(C)C=O
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(Nc1ccccc1)c1cccnc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]:[#7;a:6]:[c:7].[NH2;D1;+0:8]-[c:9](:[c:10]):[c:11]>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[NH;D2;+0:8]-[c:9](:[c:10]):[c:11])-[c:3](:[c:4]):[c:5]:[#7;a:6]:[c:7]
78.3
[{"value": 78.3, "product": "C(C)(C)(C)OC(NC1=C(C=CC=C1)NC(=O)C=1C=NC(=CC1)C#N)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
5
CELSIUS
null
null
To a solution of 444 mg (3.0 mmol) 6-cyano-nicotinic acid and 354 mg (3.5 mmol) N-methylmorpholine in 7 ml DMF at −20° C. was added 450 mg (3.3 mmol) isobutyl chloroformate. The reaction mixture was warmed to 5° C., and 625 mg (3.0 mmol) mono-boc-ortho-phenylenediamine was added. The reaction mixture was warmed to rt o...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccncc1
HO-
CN(C)C=O
5
null
CC(C)(C)OC(=O)Nc1ccccc1N.N#Cc1ccc(C(=O)O)cn1>CN(C)C=O>CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(C#N)nc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-5d0d19c1f38d4ac39a2931cfcb53fdfb
CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(C#N)nc1>>CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(CN)nc1
C(C)(C)(C)OC(NC1=C(C=CC=C1)NC(=O)C=1C=NC(=CC1)C#N)=O.C1CCOC1>>C(C)(C)(C)OC(NC1=C(C=CC=C1)NC(=O)C=1C=NC(=CC1)CN)=O
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][c:9]1[cH:10][cH:11][cH:12][cH:13][c:14]1[NH:15][C:16](=[O:17])[c:18]1[cH:19][cH:20][c:21]([C:22]#[N:23])[n:24][cH:25]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][c:9]1[cH:10][cH:11][cH:12][cH:13][c:14]1[NH:15][C:16](=[O:17])[c:18]1[cH:19][cH:20][c:21](...
CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(C#N)nc1
CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(CN)nc1
null
[Pd]
CO
Reduction
Reduction of nitrile to amine
65bec2d9f430701d30dc9fcbe1c5418f3dfa174d67be035c50edfc71895dc9c7
e8d1bc928b94bd4f5bf4b23363ce8f88b1ce7d146ba93829e7b8ad8dbe0007a7
O=C(Nc1ccccc1)c1cccnc1
[N;H0;D1;+0:1]#[C;H0;D2;+0:2]-[c:3](:[c:4]):[#7;a:5]:[c:6]>>[NH2;D1;+0:1]-[CH2;D2;+0:2]-[c:3](:[c:4]):[#7;a:5]:[c:6]
87.2
[{"value": 87.2, "product": "C(C)(C)(C)OC(NC1=C(C=CC=C1)NC(=O)C=1C=NC(=CC1)CN)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3.5
HOUR
In a flask, 2920 mg (8.72 mmol) {2-[(6-Cyano-pyridine-3-carbonyl)-amino]-phenyl}-carbamic acid t-butyl ester and 1000 mg Pd (10% on carbon) were placed under nitrogen and 10 ml THF and 120 ml methanol were added. The starting material was hydrogenated under atmospheric pressure and at rt for 3.5 h. The catalyst was fil...
10.6084/m9.figshare.5104873.v1
null
Nitrile
Primary amine
null
null
c1ccccc1.c1ccncc1
null
[Pd].CO
null
3.5
CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(C#N)nc1>[Pd].CO>CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(CN)nc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-b17ff0364e5a47e0aa4d2f4b50d032a6
C=CCN(CC=C)Cc1ccc(C(=O)OC)s1>>C=CCN(CC=C)Cc1ccc(C(=O)O)s1
COC(=O)C=1SC(=CC1)CN(CC=C)CC=C.[OH-].[K+]>>C(C=C)N(CC=C)CC1=CC=C(S1)C(=O)O
C[O:15][C:13]([c:12]1[cH:11][cH:10][c:9]([CH2:8][N:4]([CH2:3][CH:2]=[CH2:1])[CH2:5][CH:6]=[CH2:7])[s:16]1)=[O:14]>>[CH2:1]=[CH:2][CH2:3][N:4]([CH2:5][CH:6]=[CH2:7])[CH2:8][c:9]1[cH:10][cH:11][c:12]([C:13](=[O:14])[OH:15])[s:16]1
C=CCN(CC=C)Cc1ccc(C(=O)OC)s1
C=CCN(CC=C)Cc1ccc(C(=O)O)s1
null
null
CO
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccsc1
C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[#16;a:5]>>[#16;a:5]:[c:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1]
95.3
[{"value": 95.3, "product": "C(C=C)N(CC=C)CC1=CC=C(S1)C(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
50
CELSIUS
1
HOUR
To a solution of 4.5 g (17.9 mmol) 5-diallylaminomethyl-thiophene-2-carboxylic acid methyl ester in 45 ml methanol were added to 17.9 ml of a 1 N aqueous solution of KOH (17.9 mmol). The reaction mixture was stirred at 50° C. for 16 h and 1 h at reflux. The solvent was evaporated, 20 ml water was added to the residue a...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccsc1
Other
CO
50
1
C=CCN(CC=C)Cc1ccc(C(=O)OC)s1>CO>C=CCN(CC=C)Cc1ccc(C(=O)O)s1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-b8e9914bc2ed46f08901e363f3b422c0
C=CCN(CC=C)Cc1ccc(C(=O)O)s1.CC(C)(C)OC(=O)Nc1ccccc1N>>C=CCN(CC=C)Cc1ccc(C(=O)Nc2ccccc2NC(=O)OC(C)(C)C)s1
C(=O)(OC(C)(C)C)NC1=C(C=CC=C1)N.C(C=C)N(CC=C)CC1=CC=C(S1)C(=O)O.C(=O)(N1C=NC=C1)N1C=NC=C1>>C(C)(C)(C)OC(NC1=C(C=CC=C1)NC(=O)C=1SC(=CC1)CN(CC=C)CC=C)=O
O[C:13]([c:12]1[cH:11][cH:10][c:9]([CH2:8][N:4]([CH2:3][CH:2]=[CH2:1])[CH2:5][CH:6]=[CH2:7])[s:30]1)=[O:14].[NH2:15][c:16]1[cH:17][cH:18][cH:19][cH:20][c:21]1[NH:22][C:23](=[O:24])[O:25][C:26]([CH3:27])([CH3:28])[CH3:29]>>[CH2:1]=[CH:2][CH2:3][N:4]([CH2:5][CH:6]=[CH2:7])[CH2:8][c:9]1[cH:10][cH:11][c:12]([C:13](=[O:14])...
C=CCN(CC=C)Cc1ccc(C(=O)O)s1.CC(C)(C)OC(=O)Nc1ccccc1N
C=CCN(CC=C)Cc1ccc(C(=O)Nc2ccccc2NC(=O)OC(C)(C)C)s1
null
null
C1CCOC1
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(Nc1ccccc1)c1cccs1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#16;a:5]:[c:6].[NH2;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[NH;D2;+0:7]-[c:8](:[c:9]):[c:10])-[c:3](:[c:4]):[#16;a:5]:[c:6]
84.3
[{"value": 84.3, "product": "C(C)(C)(C)OC(NC1=C(C=CC=C1)NC(=O)C=1SC(=CC1)CN(CC=C)CC=C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
45
MINUTE
To a solution of 2.70 g (11.38 mmol) 5-diallylaminomethyl-thiophene-2-carboxylic acid in 50 ml THF was added 2.03 g (12.51 mmol) carbonyldiimidazol. After 45 min at rt, 2.48 g (11.95 mmol) mono-boc-ortho-phenylenediamine were added to the reaction mixture, and it was stirred for 3 h at rt. The solvent was evaporated an...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccsc1.c1ccccc1
HO-
C1CCOC1
null
0.75
C=CCN(CC=C)Cc1ccc(C(=O)O)s1.CC(C)(C)OC(=O)Nc1ccccc1N>C1CCOC1>C=CCN(CC=C)Cc1ccc(C(=O)Nc2ccccc2NC(=O)OC(C)(C)C)s1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-fde35acb794e44f89d09261016546ce8
CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(CN)s1.CCC(C)CC(=O)O>>CCC(C)CC(=O)NCc1ccc(C(=O)Nc2ccccc2N)s1
CC(CC(=O)O)CC.C(=O)(N1C=NC=C1)N1C=NC=C1.FC(C(=O)O)(F)F.C(=O)(O)[O-].[Na+].C(C)(C)(C)OC(NC1=C(C=CC=C1)NC(=O)C=1SC(=CC1)CN)=O>>NC1=C(C=CC=C1)NC(=O)C=1SC(=CC1)CNC(CC(CC)C)=O
CC(C)(C)OC(=O)[NH:23][c:22]1[c:17]([NH:16][C:14]([c:13]2[cH:12][cH:11][c:10]([CH2:9][NH2:8])[s:24]2)=[O:15])[cH:18][cH:19][cH:20][cH:21]1.O[C:6]([CH2:5][CH:3]([CH2:2][CH3:1])[CH3:4])=[O:7]>>[CH3:1][CH2:2][CH:3]([CH3:4])[CH2:5][C:6](=[O:7])[NH:8][CH2:9][c:10]1[cH:11][cH:12][c:13]([C:14](=[O:15])[NH:16][c:17]2[cH:18][cH:...
CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(CN)s1.CCC(C)CC(=O)O
CCC(C)CC(=O)NCc1ccc(C(=O)Nc2ccccc2N)s1
null
null
C1CCOC1
Acylation
OtherReaction
b4c20342f55b434660078663f02be082076e2ff9b9068db91acc0b381022a32e
e525bb030a9f5f4a2fc47bce923bf921a3769ce3300b3fa2600575194671a3f3
O=C(Nc1ccccc1)c1cccs1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4].[#16;a:5]:[c:6]-[C:7]-[NH2;D1;+0:8].O-[C;H0;D3;+0:9](=[O;D1;H0:10])-[C:11]-[C:12]>>[#16;a:5]:[c:6]-[C:7]-[NH;D2;+0:8]-[C;H0;D3;+0:9](=[O;D1;H0:10])-[C:11]-[C:12].[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
59.4
[{"value": 59.4, "product": "NC1=C(C=CC=C1)NC(=O)C=1SC(=CC1)CNC(CC(CC)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
To a solution of 33.43 mg (0.288 mmol) 3-methylpentanoic acid in 1 ml THF were added 46.67 mg (0.288 mmol) 1,1′-carbonyldiimidazol. After 1 h at rt 100 mg (0.288 mmol) {2-[(5-aminomethyl-thiophene-2-carbonyl)-amino]-phenyl}-carbamic acid t-butyl ester were added and the reaction mixture was stirred for 3 h at rt. 1.7 m...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Carboxylic acid.Ether.Primary amine.Boc
Secondary amide.Primary amine
null
null
c1ccsc1.c1ccccc1
HO-
C1CCOC1
null
3
CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(CN)s1.CCC(C)CC(=O)O>C1CCOC1>CCC(C)CC(=O)NCc1ccc(C(=O)Nc2ccccc2N)s1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-e05e980ae8ac4510ba2589fcb4989b89
CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(CN)s1.O=C(n1ccnc1)n1ccnc1>>C#CCNC(=O)NCc1ccc(C(=O)Nc2ccccc2N)s1
C(=O)(N1C=NC=C1)N1C=NC=C1.C(C)(C)(C)OC(NC1=C(C=CC=C1)NC(=O)C=1SC(=CC1)CN)=O.FC(C(=O)O)(F)F.C(=O)(O)[O-].[Na+]>>NC1=C(C=CC=C1)NC(=O)C=1SC(=CC1)CNC(=O)NCC#C
C[C:2](C)(O[C:5](=[O:6])[NH:22][c:21]1[c:16]([NH:15][C:13]([c:12]2[cH:11][cH:10][c:9]([CH2:8][NH2:7])[s:23]2)=[O:14])[cH:17][cH:18][cH:19][cH:20]1)[CH3:1].O=C(n1ccnc1)n1cc[n:4][cH:3]1>>[CH:1]#[C:2][CH2:3][NH:4][C:5](=[O:6])[NH:7][CH2:8][c:9]1[cH:10][cH:11][c:12]([C:13](=[O:14])[NH:15][c:16]2[cH:17][cH:18][cH:19][cH:20]...
CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(CN)s1.O=C(n1ccnc1)n1ccnc1
C#CCNC(=O)NCc1ccc(C(=O)Nc2ccccc2N)s1
null
null
C1CCOC1
Acylation
OtherReaction
196c848380cb989baef99af6daf345ce72cf1e7cc10cef1e65e85edd91b8e7f6
0f36a742e3b3789f6d9b6dd0e635f3401096f12ad61afd9387b414e7c3f77b3a
O=C(Nc1ccccc1)c1cccs1
C-[C;H0;D4;+0:1](-C)(-[CH3;D1;+0:2])-O-[C;H0;D3;+0:3](=[O;D1;H0:4])-[NH;D2;+0:5]-[c:6](:[c:7]):[c:8].[#16;a:9]:[c:10]-[C:11]-[NH2;D1;+0:12].O=C(-n1:[cH;D2;+0:13]:[n;H0;D2;+0:14]:c:c:1)-n1:c:c:n:c:1>>[#16;a:9]:[c:10]-[C:11]-[NH;D2;+0:12]-[C;H0;D3;+0:3](=[O;D1;H0:4])-[NH;D2;+0:14]-[CH2;D2;+0:13]-[C;H0;D2;+0:1]#[CH;D1;+0:...
null
[]
null
null
1
HOUR
To a solution of 15.8 mg (0.288 mmol) in 1 ml THF were added 46.7 mg (0.288 mmol) 1,1′-carbonyldiimidazol. After 1 h at rt 100 mg (0.288 mmol) {2-[(5-Aminomethyl-thiophene-2-carbonyl)-amino]-phenyl}-carbamic acid t-butyl ester were added and the reaction mixture was stirred for 1 h at rt. 1.7 ml trifluoroacetic acid we...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Primary amine.Boc
Urea.Primary amine.Alkyne
c1c[nH]cn1.c1c[nH]cn1
null
c1ccsc1.c1ccccc1
HO-
C1CCOC1
null
1
CC(C)(C)OC(=O)Nc1ccccc1NC(=O)c1ccc(CN)s1.O=C(n1ccnc1)n1ccnc1>C1CCOC1>C#CCNC(=O)NCc1ccc(C(=O)Nc2ccccc2N)s1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-f049805b02c647ba9683e13a05b400db
CCOC(=O)C(NC(C)=O)C(=O)OCC.COc1cccc([N+](=O)[O-])c1CBr>>CCOC(=O)C(Cc1c(OC)cccc1[N+](=O)[O-])(NC(C)=O)C(=O)OCC
COC1=C(CBr)C(=CC=C1)[N+](=O)[O-].[Na].C(C)(=O)NC(C(=O)OCC)C(=O)OCC>>C(C)(=O)NC(C(=O)OCC)(C(=O)OCC)CC1=C(C=CC=C1[N+](=O)[O-])OC
[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]([NH:19][C:20]([CH3:21])=[O:22])[C:23](=[O:24])[O:25][CH2:26][CH3:27].Br[CH2:7][c:8]1[c:9]([O:10][CH3:11])[cH:12][cH:13][cH:14][c:15]1[N+:16](=[O:17])[O-:18]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[C:6]([CH2:7][c:8]1[c:9]([O:10][CH3:11])[cH:12][cH:13][cH:14][c:15]1[N+:16](=[O:17])[O-:18]...
CCOC(=O)C(NC(C)=O)C(=O)OCC.COc1cccc([N+](=O)[O-])c1CBr
CCOC(=O)C(Cc1c(OC)cccc1[N+](=O)[O-])(NC(C)=O)C(=O)OCC
null
null
O1CCCC1.C(C)O
C-C Coupling
OtherReaction
8175b6573d6439ec7ccc45bf6b48843ab56b46dccfc6504384c4766d09f35cc7
d1817e44576d3a158547867a56245217a593d4f828a6d6dfaa8ed11276894e44
c1ccccc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[C:5]-[#8:6]-[C:7](=[O;D1;H0:8])-[CH;D3;+0:9](-[#7:10]-[C:11](-[C;D1;H3:12])=[O;D1;H0:13])-[C:14](=[O;D1;H0:15])-[#8:16]-[C:17]>>[C:5]-[#8:6]-[C:7](=[O;D1;H0:8])-[C;H0;D4;+0:9](-[#7:10]-[C:11](-[C;D1;H3:12])=[O;D1;H0:13])(-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4])-[C:14](=[O;D1;H0:15])-[#8...
80.8
[{"value": 80.8, "product": "C(C)(=O)NC(C(=O)OCC)(C(=O)OCC)CC1=C(C=CC=C1[N+](=O)[O-])OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
15
MINUTE
Sodium metal (1.15 g) was dissolved in absolute ethanol (500 mL), and to the resulting solution was added diethyl 2-acetylaminomalonate (9.1 g). After 15 min at room temperature, a solution of 2-methoxy-6-nitrobenzyl bromide (J. Med. Chem. 1977, 20, 190–196) (8.6 g) in tetrahydrofuran (25 mL) was added over 2 min. Afte...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Ester
Ester.Ester
null
null
c1ccccc1
HBr
O1CCCC1.C(C)O
null
0.25
CCOC(=O)C(NC(C)=O)C(=O)OCC.COc1cccc([N+](=O)[O-])c1CBr>O1CCCC1.C(C)O>CCOC(=O)C(Cc1c(OC)cccc1[N+](=O)[O-])(NC(C)=O)C(=O)OCC
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-1b8f64453b0740288fbfa5f4cd0e66e6
CCOC(=O)C1(NNC(C)=O)Cc2c(cccc2OC)NC1=O>>COc1cccc2c1CC(N)C(=O)N2
C(C)(=O)NNC1(C(NC2=CC=CC(=C2C1)OC)=O)C(=O)OCC.Cl>>Cl.NC1C(NC2=CC=CC(=C2C1)OC)=O
CCOC(=O)[C:10]1([NH:11]NC(C)=O)[CH2:9][c:8]2[c:3]([O:2][CH3:1])[cH:4][cH:5][cH:6][c:7]2[NH:14][C:12]1=[O:13]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][c:7]2[c:8]1[CH2:9][CH:10]([NH2:11])[C:12](=[O:13])[NH:14]2
CCOC(=O)C1(NNC(C)=O)Cc2c(cccc2OC)NC1=O
COc1cccc2c1CC(N)C(=O)N2
null
null
null
Reduction
OtherReaction
2c338b3fc2cd663fdeee6d151fc6977eb4ab6d56c1ee0f9a83292028af3cb257
e1ff1c0fc834910ed4e0ca9feef7d4e05e8e69a52715b51aaad0c2f8843bdde1
O=C1CCc2ccccc2N1
C-C-O-C(=O)-[C;H0;D4;+0:1]1(-[NH;D2;+0:2]-N-C(-C)=O)-[C:3]-[c:4]:[c:5]-[#7:6]-[C:7]-1=[O;D1;H0:8]>>[NH2;D1;+0:2]-[CH;D3;+0:1]1-[C:3]-[c:4]:[c:5]-[#7:6]-[C:7]-1=[O;D1;H0:8]
null
[]
null
null
null
null
A mixture of 3-acetamidoamino-3-carboethoxy-5-methoxy-3,4-dihydrocarbostyril (5.7 g) and 6 M aqueous hydrochloric acid (75 mL) was refluxed for 6 h. This mixture was evaporated to a solid which was triturated with acetonitrile. Filtration provided 3-amino-5-methoxy-3,4-dihydrocarbostyril hydrochloride (3.8 g, mp 301–30...
10.6084/m9.figshare.5104873.v1
null
Acylhydrazine.Ester
Primary amine
c1ccc2c(c1)CCCN2
c1ccc2c(c1)CCCN2
c1ccc2c(c1)CCCN2
HO-
null
null
null
CCOC(=O)C1(NNC(C)=O)Cc2c(cccc2OC)NC1=O>>COc1cccc2c1CC(N)C(=O)N2
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-882c13e9df2048968dbb8b5b49176140
CC(C)(C)OC(=O)N[C@@H]1Cc2ccccc2NC1=O>>N[C@@H]1Cc2ccccc2NC1=O
C(C)(C)(C)OC(=O)N[C@H]1C(NC2=CC=CC=C2C1)=O.Cl>>Cl.N[C@H]1C(NC2=CC=CC=C2C1)=O
CC(C)(C)OC(=O)[NH:2][C@@H:3]1[CH2:4][c:5]2[cH:6][cH:7][cH:8][cH:9][c:10]2[NH:11][C:12]1=[O:13]>>[NH2:2][C@@H:3]1[CH2:4][c:5]2[cH:6][cH:7][cH:8][cH:9][c:10]2[NH:11][C:12]1=[O:13]
CC(C)(C)OC(=O)N[C@@H]1Cc2ccccc2NC1=O
N[C@@H]1Cc2ccccc2NC1=O
null
null
O1CCOCC1
Reduction
Hydrogenolysis of amides/imides/carbamates
3c33dd2a2d355ee5ba0287367e209aa147a39aa00607f0c95fb2bf1ade45d014
c5b5dffe7dd8beebdc1baa8b5b05300a9f7079e65dcfd42ade6f8a77ff09537d
O=C1CCc2ccccc2N1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2](-[C:3])-[C:4](=[O;D1;H0:5])-[#7:6]-[c:7]>>[C:3]-[C:2](-[NH2;D1;+0:1])-[C:4](=[O;D1;H0:5])-[#7:6]-[c:7]
null
[]
null
null
null
null
(R)-3-t-butyloxycarbonylamino-3,4-dihydrocarbostyril (178 mg) was dissolved in 4 M hydrogen chloride in 1,4-dioxane solution (10 mL) at 0° C. After 1 h the solution was slowly warmed to room temperature over 2 h. The solvent was evaporated under vacuum, and the residue was twice taken up in toluene (10 mL) and evaporat...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Primary amine
null
null
c1ccc2c(c1)CCCN2
HO-
O1CCOCC1
null
null
CC(C)(C)OC(=O)N[C@@H]1Cc2ccccc2NC1=O>O1CCOCC1>N[C@@H]1Cc2ccccc2NC1=O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-4f9378c9da544df4bb857bb8e09642db
N[C@@H]1Cc2ccccc2NC1=O.O=C(O)c1cc2cc(Cl)ccc2[nH]1>>O=C(N[C@@H]1Cc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1
C(C)(C)N(CC)C(C)C.Cl.N[C@H]1C(NC2=CC=CC=C2C1)=O.ClC=1C=C2C=C(NC2=CC1)C(=O)O.ON1N=NC2=C1N=CC=C2.Cl.CN(CCCN=C=NCC)C>>ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@H]1C(NC2=CC=CC=C2C1)=O
[NH2:3][C@@H:4]1[CH2:5][c:6]2[cH:7][cH:8][cH:9][cH:10][c:11]2[NH:12][C:13]1=[O:14].O[C:2](=[O:1])[c:15]1[cH:16][c:17]2[cH:18][c:19]([Cl:20])[cH:21][cH:22][c:23]2[nH:24]1>>[O:1]=[C:2]([NH:3][C@@H:4]1[CH2:5][c:6]2[cH:7][cH:8][cH:9][cH:10][c:11]2[NH:12][C:13]1=[O:14])[c:15]1[cH:16][c:17]2[cH:18][c:19]([Cl:20])[cH:21][cH:2...
N[C@@H]1Cc2ccccc2NC1=O.O=C(O)c1cc2cc(Cl)ccc2[nH]1
O=C(N[C@@H]1Cc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1
null
null
C(C)(=O)OCC.O1CCCC1
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(N[C@@H]1Cc2ccccc2NC1=O)c1cc2ccccc2[nH]1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6].[C:7]-[C:8](-[NH2;D1;+0:9])-[C:10](=[O;D1;H0:11])-[#7:12]-[c:13]>>[C:7]-[C:8](-[NH;D2;+0:9]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6])-[C:10](=[O;D1;H0:11])-[#7:12]-[c:13]
81.2
[{"value": 81.2, "product": "ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@H]1C(NC2=CC=CC=C2C1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
Alternatively, (R)-3-amino-3,4-dihydrocarbostyril hydrochloride (95 mg) was added to a mixture of tetrahydrofuran (10 mL), 5-chloroindole-2-carboxylic acid (103 mg), 1-hydroxy-7-azabenzotriazole (85 mg), and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (120 mg) at room temperature. Diisopropylethylamin...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccc2c(c1)CCCN2.c1ccc2[nH]ccc2c1
HO-
C(C)(=O)OCC.O1CCCC1
null
2
N[C@@H]1Cc2ccccc2NC1=O.O=C(O)c1cc2cc(Cl)ccc2[nH]1>C(C)(=O)OCC.O1CCCC1>O=C(N[C@@H]1Cc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-2512700fc8144e54b4578077e1a943bc
O=C(N[C@@H]1Cc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1>>O=C(N[C@H]1Cc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1
ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@H]1C(NC2=CC=CC=C2C1)=O.C(C)(C)(C)OC(=O)N[C@H]1C(NC2=CC=CC=C2C1)=O.ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@H]1C(NC2=CC=CC=C2C1)=O>>ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@@H]1C(NC2=CC=CC=C2C1)=O
[O:1]=[C:2]([NH:3][C@@H:4]1[CH2:5][c:6]2[cH:7][cH:8][cH:9][cH:10][c:11]2[NH:12][C:13]1=[O:14])[c:15]1[cH:16][c:17]2[cH:18][c:19]([Cl:20])[cH:21][cH:22][c:23]2[nH:24]1>>[O:1]=[C:2]([NH:3][C@H:4]1[CH2:5][c:6]2[cH:7][cH:8][cH:9][cH:10][c:11]2[NH:12][C:13]1=[O:14])[c:15]1[cH:16][c:17]2[cH:18][c:19]([Cl:20])[cH:21][cH:22][c...
O=C(N[C@@H]1Cc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1
O=C(N[C@H]1Cc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1
null
null
null
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
O=C(N[C@H]1Cc2ccccc2NC1=O)c1cc2ccccc2[nH]1
null
null
[]
null
null
null
null
The title compound was prepared from (S)-3-t-butyloxycarbonylamino-3,4-dihydrocarbostyril (prepared in Example 5) by the procedures described for the preparation of (R)-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyril (Example 5) from (R)-3-t-butyloxycarbonylamino-3,4-dihydrocarbostyril. HPLC/MS [M+H]+, 340; [...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
c1ccc2c(c1)CCCN2.c1ccc2[nH]ccc2c1
null
null
null
null
O=C(N[C@@H]1Cc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1>>O=C(N[C@H]1Cc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-d12725ce188849a28139487c1b120a88
CC(C)(C)OC(=O)N[C@@H]1Cc2ccccc2NC1=O.COC(=O)CBr>>COC(=O)CN1C(=O)[C@H](NC(=O)OC(C)(C)C)Cc2ccccc21
C(C)(C)(C)OC(=O)N[C@H]1C(NC2=CC=CC=C2C1)=O.BrCC(=O)OC.C(C)(=O)OCC.C[O-].[Na+]>>C(C)(C)(C)OC(=O)N[C@H]1C(N(C2=CC=CC=C2C1)CC(=O)OC)=O
[NH:6]1[C:7](=[O:8])[C@H:9]([NH:10][C:11](=[O:12])[O:13][C:14]([CH3:15])([CH3:16])[CH3:17])[CH2:18][c:19]2[cH:20][cH:21][cH:22][cH:23][c:24]21.Br[CH2:5][C:3]([O:2][CH3:1])=[O:4]>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][N:6]1[C:7](=[O:8])[C@H:9]([NH:10][C:11](=[O:12])[O:13][C:14]([CH3:15])([CH3:16])[CH3:17])[CH2:18][c:19]2[cH:...
CC(C)(C)OC(=O)N[C@@H]1Cc2ccccc2NC1=O.COC(=O)CBr
COC(=O)CN1C(=O)[C@H](NC(=O)OC(C)(C)C)Cc2ccccc21
null
null
O.O1CCCC1
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
00bdf42034ad419e8a7421c967f14ba303b548b011e99dd40ab321f2309531bf
933a6f1013d44497c9c5902b73c24fbdc7813d20b886bdbc4c670d5b43ca2182
O=C1CCc2ccccc2N1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5].[C:6]-[C:7](=[O;D1;H0:8])-[NH;D2;+0:9]-[c:10](:[c:11]):[c:12]>>[C:6]-[C:7](=[O;D1;H0:8])-[N;H0;D3;+0:9](-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5])-[c:10](:[c:11]):[c:12]
72.4
[{"value": 72.4, "product": "C(C)(C)(C)OC(=O)N[C@H]1C(N(C2=CC=CC=C2C1)CC(=O)OC)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
(R)-3-t-butyloxycarbonylamino-3,4-dihydrocarbostyril (26 mg), as prepared in Example 5, was dissolved in tetrahydrofuran (5 mL) at room temperature under argon. To the stirring solution was added methyl bromoacetate (31 mg), followed by sodium methoxide (26 mg). The resulting suspension was stirred for 30 min before di...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Secondary amide
Ester.Tertiary amide
c1ccc2c(c1)CCCN2
c1ccc2c(c1)CCC[NH]2
c1ccc2c(c1)CCC[NH]2
HBr
O.O1CCCC1
null
null
CC(C)(C)OC(=O)N[C@@H]1Cc2ccccc2NC1=O.COC(=O)CBr>O.O1CCCC1>COC(=O)CN1C(=O)[C@H](NC(=O)OC(C)(C)C)Cc2ccccc21
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-78cfe89bac18470c801689497e4e731f
COC(=O)CN1C(=O)[C@H](NC(=O)OC(C)(C)C)Cc2ccccc21>>COC(=O)CN1C(=O)[C@H](N)Cc2ccccc21
C(C)(C)(C)OC(=O)N[C@H]1C(N(C2=CC=CC=C2C1)CC(=O)OC)=O.Cl>>Cl.N[C@H]1C(N(C2=CC=CC=C2C1)CC(=O)OC)=O
CC(C)(C)OC(=O)[NH:10][C@H:9]1[C:7](=[O:8])[N:6]([CH2:5][C:3]([O:2][CH3:1])=[O:4])[c:17]2[c:12]([cH:13][cH:14][cH:15][cH:16]2)[CH2:11]1>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][N:6]1[C:7](=[O:8])[C@H:9]([NH2:10])[CH2:11][c:12]2[cH:13][cH:14][cH:15][cH:16][c:17]21
COC(=O)CN1C(=O)[C@H](NC(=O)OC(C)(C)C)Cc2ccccc21
COC(=O)CN1C(=O)[C@H](N)Cc2ccccc21
null
null
O1CCOCC1
Reduction
Hydrogenolysis of amides/imides/carbamates
3c33dd2a2d355ee5ba0287367e209aa147a39aa00607f0c95fb2bf1ade45d014
c5b5dffe7dd8beebdc1baa8b5b05300a9f7079e65dcfd42ade6f8a77ff09537d
O=C1CCc2ccccc2N1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2](-[C:3])-[C:4](=[O;D1;H0:5])-[#7:6](-[C:7]-[C:8](-[#8:9])=[O;D1;H0:10])-[c:11]>>[#8:9]-[C:8](=[O;D1;H0:10])-[C:7]-[#7:6](-[c:11])-[C:4](=[O;D1;H0:5])-[C:2](-[NH2;D1;+0:1])-[C:3]
null
[]
null
null
null
null
(R)-3-t-butyloxycarbonylamino-1-carbomethoxymethyl-3,4-dihydrocarbostyril (20 mg) was dissolved in 4 M hydrogen chloride in 1,4-dioxane solution (5 mL) at room temperature. After 1 h the solvent was evaporated under vacuum, and the residue was twice taken up in toluene (10 mL) and evaporated under vacuum to provide (R)...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Primary amine
null
null
c1ccc2c(c1)CCC[NH]2
HO-
O1CCOCC1
null
null
COC(=O)CN1C(=O)[C@H](NC(=O)OC(C)(C)C)Cc2ccccc21>O1CCOCC1>COC(=O)CN1C(=O)[C@H](N)Cc2ccccc21
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-c28c8a5e0d064f24bb8eb2c35c7f7138
COC(=O)CN1C(=O)[C@H](N)Cc2ccccc21.O=C(O)c1cc2cc(Cl)ccc2[nH]1>>COC(=O)CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
C(C)(C)N(CC)C(C)C.Cl.N[C@H]1C(N(C2=CC=CC=C2C1)CC(=O)OC)=O.ClC=1C=C2C=C(NC2=CC1)C(=O)O.ON1N=NC2=C1N=CC=C2.Cl.CN(CCCN=C=NCC)C>>C(=O)(OC)CN1C(=O)[C@@H](CC2=CC=CC=C12)NC(=O)C=1NC2=CC=C(C=C2C1)Cl
[CH3:1][O:2][C:3](=[O:4])[CH2:5][N:6]1[C:7](=[O:8])[C@H:9]([NH2:10])[CH2:23][c:24]2[cH:25][cH:26][cH:27][cH:28][c:29]21.O[C:11](=[O:12])[c:13]1[cH:14][c:15]2[cH:16][c:17]([Cl:18])[cH:19][cH:20][c:21]2[nH:22]1>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][N:6]1[C:7](=[O:8])[C@H:9]([NH:10][C:11](=[O:12])[c:13]2[cH:14][c:15]3[cH:16][...
COC(=O)CN1C(=O)[C@H](N)Cc2ccccc21.O=C(O)c1cc2cc(Cl)ccc2[nH]1
COC(=O)CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
null
null
C(C)(=O)OCC.O1CCCC1
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(N[C@@H]1Cc2ccccc2NC1=O)c1cc2ccccc2[nH]1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6].[#8:7]-[C:8](=[O;D1;H0:9])-[C:10]-[#7:11](-[c:12])-[C:13](=[O;D1;H0:14])-[C:15](-[NH2;D1;+0:16])-[C:17]>>[#8:7]-[C:8](=[O;D1;H0:9])-[C:10]-[#7:11](-[c:12])-[C:13](=[O;D1;H0:14])-[C:15](-[NH;D2;+0:16]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6])-[...
26.3
[{"value": 26.3, "product": "C(=O)(OC)CN1C(=O)[C@@H](CC2=CC=CC=C12)NC(=O)C=1NC2=CC=C(C=C2C1)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
Alternatively, (R)-3-amino-1-carbomethoxymethyl-3,4-dihydrocarbostyril hydrochloride (19 mg) was added to a mixture of tetrahydrofuran (10 mL), 5-chloroindole-2-carboxylic acid (15 mg), 1-hydroxy-7-azabenzotriazole (12 mg), and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (16 mg) at room temperature. D...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccc2[nH]ccc2c1.c1ccc2c(c1)CCC[NH]2
HO-
C(C)(=O)OCC.O1CCCC1
null
16
COC(=O)CN1C(=O)[C@H](N)Cc2ccccc21.O=C(O)c1cc2cc(Cl)ccc2[nH]1>C(C)(=O)OCC.O1CCCC1>COC(=O)CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-f6b32ea6655540abb07919434d96aeb2
COC(=O)CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21>>COC(=O)CN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
C(=O)(OC)CN1C(=O)[C@@H](CC2=CC=CC=C12)NC(=O)C=1NC2=CC=C(C=C2C1)Cl.C(C)(C)(C)OC(=O)N[C@H]1C(NC2=CC=CC=C2C1)=O.ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@H]1C(NC2=CC=CC=C2C1)=O>>C(=O)(OC)CN1C(=O)[C@H](CC2=CC=CC=C12)NC(=O)C=1NC2=CC=C(C=C2C1)Cl
[CH3:1][O:2][C:3](=[O:4])[CH2:5][N:6]1[C:7](=[O:8])[C@H:9]([NH:10][C:11](=[O:12])[c:13]2[cH:14][c:15]3[cH:16][c:17]([Cl:18])[cH:19][cH:20][c:21]3[nH:22]2)[CH2:23][c:24]2[cH:25][cH:26][cH:27][cH:28][c:29]21>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][N:6]1[C:7](=[O:8])[C@@H:9]([NH:10][C:11](=[O:12])[c:13]2[cH:14][c:15]3[cH:16][c:...
COC(=O)CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
COC(=O)CN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
null
null
null
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
O=C(N[C@H]1Cc2ccccc2NC1=O)c1cc2ccccc2[nH]1
null
null
[]
null
null
null
null
The title compound was prepared from (S)-3-t-butyloxycarbonylamino-3,4-dihydrocarbostyril (prepared in Example 5) by the procedures described for the preparation of (R)-1-carbomethoxymethyl-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyril (Example 7) from (R)-3-t-butyloxycarbonylamino-3,4-dihydrocarbostyril. H...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
c1ccc2[nH]ccc2c1.c1ccc2c(c1)CCC[NH]2
null
null
null
null
COC(=O)CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21>>COC(=O)CN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-813d8b6b01f04099a39edd6df9f74699
COC(=O)CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21>>O=C(O)CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
C(=O)(OC)CN1C(=O)[C@@H](CC2=CC=CC=C12)NC(=O)C=1NC2=CC=C(C=C2C1)Cl.O.[OH-].[Li+].Cl>>C(=O)(O)CN1C(=O)[C@@H](CC2=CC=CC=C12)NC(=O)C=1NC2=CC=C(C=C2C1)Cl
C[O:3][C:2](=[O:1])[CH2:4][N:5]1[C:6](=[O:7])[C@H:8]([NH:9][C:10](=[O:11])[c:12]2[cH:13][c:14]3[cH:15][c:16]([Cl:17])[cH:18][cH:19][c:20]3[nH:21]2)[CH2:22][c:23]2[cH:24][cH:25][cH:26][cH:27][c:28]21>>[O:1]=[C:2]([OH:3])[CH2:4][N:5]1[C:6](=[O:7])[C@H:8]([NH:9][C:10](=[O:11])[c:12]2[cH:13][c:14]3[cH:15][c:16]([Cl:17])[cH...
COC(=O)CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
O=C(O)CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
null
null
CO.O.O1CCCC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(N[C@@H]1Cc2ccccc2NC1=O)c1cc2ccccc2[nH]1
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]
95.6
[{"value": 95.6, "product": "C(=O)(O)CN1C(=O)[C@@H](CC2=CC=CC=C12)NC(=O)C=1NC2=CC=C(C=C2C1)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
(R)-1-carbomethoxymethyl-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyril (Example 7) (13 mg) was dissolved in a 2:2:1 mixture of tetrahydrofuran, methanol, and water (5 mL). Lithium hydroxide monohydrate (3 mg) was added, and the resulting mixture was stirred at room temperature for 2 h. Addition of 1.0 M aqu...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccc2[nH]ccc2c1.c1ccc2c(c1)CCC[NH]2
Other
CO.O.O1CCCC1
null
2
COC(=O)CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21>CO.O.O1CCCC1>O=C(O)CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-e27a544e111c468b84bfc09d15cd05db
O=C(O)CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21>>O=C(O)CN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
C(=O)(O)CN1C(=O)[C@@H](CC2=CC=CC=C12)NC(=O)C=1NC2=CC=C(C=C2C1)Cl.C(=O)(OC)CN1C(=O)[C@@H](CC2=CC=CC=C12)NC(=O)C=1NC2=CC=C(C=C2C1)Cl.C(=O)(OC)CN1C(=O)[C@H](CC2=CC=CC=C12)NC(=O)C=1NC2=CC=C(C=C2C1)Cl>>C(=O)(O)CN1C(=O)[C@H](CC2=CC=CC=C12)NC(=O)C=1NC2=CC=C(C=C2C1)Cl
[O:1]=[C:2]([OH:3])[CH2:4][N:5]1[C:6](=[O:7])[C@H:8]([NH:9][C:10](=[O:11])[c:12]2[cH:13][c:14]3[cH:15][c:16]([Cl:17])[cH:18][cH:19][c:20]3[nH:21]2)[CH2:22][c:23]2[cH:24][cH:25][cH:26][cH:27][c:28]21>>[O:1]=[C:2]([OH:3])[CH2:4][N:5]1[C:6](=[O:7])[C@@H:8]([NH:9][C:10](=[O:11])[c:12]2[cH:13][c:14]3[cH:15][c:16]([Cl:17])[c...
O=C(O)CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
O=C(O)CN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
null
null
null
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
O=C(N[C@H]1Cc2ccccc2NC1=O)c1cc2ccccc2[nH]1
null
null
[]
null
null
null
null
The title compound was prepared from (S)-1-carbomethoxymethyl-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyril (Example 8) by the procedures described for the preparation of (R)-1-carboxymethyl-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyril (Example 9) from (R)-1-carbomethoxymethyl-3-(5-chloroindole...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
c1ccc2[nH]ccc2c1.c1ccc2c(c1)CCC[NH]2
null
null
null
null
O=C(O)CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21>>O=C(O)CN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-53c7f65f8f8a484284f4f588533f0f5f
O=C(O)CN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21>>O=C(N[C@H]1Cc2ccccc2N(CCO)C1=O)c1cc2cc(Cl)ccc2[nH]1
C(=O)(O)CN1C(=O)[C@H](CC2=CC=CC=C12)NC(=O)C=1NC2=CC=C(C=C2C1)Cl.Cl.C(C)(=O)OCC>>OCCN1C(=O)[C@H](CC2=CC=CC=C12)NC(=O)C=1NC2=CC=C(C=C2C1)Cl
O=[C:14]([CH2:13][N:12]1[c:11]2[c:6]([cH:7][cH:8][cH:9][cH:10]2)[CH2:5][C@H:4]([NH:3][C:2](=[O:1])[c:18]2[cH:19][c:20]3[cH:21][c:22]([Cl:23])[cH:24][cH:25][c:26]3[nH:27]2)[C:16]1=[O:17])[OH:15]>>[O:1]=[C:2]([NH:3][C@H:4]1[CH2:5][c:6]2[cH:7][cH:8][cH:9][cH:10][c:11]2[N:12]([CH2:13][CH2:14][OH:15])[C:16]1=[O:17])[c:18]1[...
O=C(O)CN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
O=C(N[C@H]1Cc2ccccc2N(CCO)C1=O)c1cc2cc(Cl)ccc2[nH]1
null
null
O1CCCC1.B
Reduction
Reduction of carboxylic acid to primary alcohol
0db83a5ebe1e318b78b55461cf7eb8f7c004eef0f9e3b6666d3df4c96b5f665e
93b4621647b04d2ad2f2825215b1567f171ba61fe10d136b5db6ea0470aa4932
O=C(N[C@H]1Cc2ccccc2NC1=O)c1cc2ccccc2[nH]1
O=[C;H0;D3;+0:1](-[O;D1;H1:2])-[C:3]-[#7:4]-[C:5]=[O;D1;H0:6]>>[O;D1;H0:6]=[C:5]-[#7:4]-[C:3]-[CH2;D2;+0:1]-[O;D1;H1:2]
19
[{"value": 19.0, "product": "OCCN1C(=O)[C@H](CC2=CC=CC=C12)NC(=O)C=1NC2=CC=C(C=C2C1)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
35
CELSIUS
3
HOUR
A mixture of (S)-1-carboxymethyl-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyril (Example 10) (6 mg) in 1.0 M borane in tetrahydrofuran solution (2 mL) under argon was stirred at 35° C. for 3 h. After cooling to room temperature, 1.0 M aqueous hydrochloric acid (10 mL) and ethyl acetate (10 mL) were added. Th...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
Primary alcohol
null
null
c1ccc2c(c1)CCC[NH]2.c1ccc2[nH]ccc2c1
Other
O1CCCC1.B
35
3
O=C(O)CN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21>O1CCCC1.B>O=C(N[C@H]1Cc2ccccc2N(CCO)C1=O)c1cc2cc(Cl)ccc2[nH]1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-2a3dd76371664609a5344ed600f823e0
COC(=O)CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21.N>>NC(=O)CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
C(=O)(OC)CN1C(=O)[C@@H](CC2=CC=CC=C12)NC(=O)C=1NC2=CC=C(C=C2C1)Cl.N>>NC(=O)CN1C(=O)[C@@H](CC2=CC=CC=C12)NC(=O)C=1NC2=CC=C(C=C2C1)Cl
CO[C:2](=[O:3])[CH2:4][N:5]1[C:6](=[O:7])[C@H:8]([NH:9][C:10](=[O:11])[c:12]2[cH:13][c:14]3[cH:15][c:16]([Cl:17])[cH:18][cH:19][c:20]3[nH:21]2)[CH2:22][c:23]2[cH:24][cH:25][cH:26][cH:27][c:28]21.[NH3:1]>>[NH2:1][C:2](=[O:3])[CH2:4][N:5]1[C:6](=[O:7])[C@H:8]([NH:9][C:10](=[O:11])[c:12]2[cH:13][c:14]3[cH:15][c:16]([Cl:17...
COC(=O)CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21.N
NC(=O)CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
null
null
CO.O1CCCC1
Acylation
OtherReaction
d5b10d4f469e7a196a3b04a6a9e159a7d90514b6df5b50c1197d4b1b774c04e1
adc0ef6f6c1340dd2dbab737c85bf17fc842769181c5db1a2b4f82b391b28f9f
O=C(N[C@@H]1Cc2ccccc2NC1=O)c1cc2ccccc2[nH]1
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[#7:4]-[C:5]=[O;D1;H0:6].[NH3;D0;+0:7]>>[NH2;D1;+0:7]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[#7:4]-[C:5]=[O;D1;H0:6]
null
[]
null
null
16
HOUR
(R)-1-carbomethoxymethyl-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyril (Example 7) (5.6 mg) was dissolved in a mixture of tetrahydrofuran (2 mL) and 2 M ammonia in methanol solution (2 mL). After stirring for 16 h at room temperature, the solvent was evaporated under vacuum and the residue was coevaporated ...
10.6084/m9.figshare.5104873.v1
null
Ester
Primary amide
null
null
c1ccc2[nH]ccc2c1.c1ccc2c(c1)CCC[NH]2
HO-
CO.O1CCCC1
null
16
COC(=O)CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21.N>CO.O1CCCC1>NC(=O)CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-f50d546389dc4eed91959315280729a1
COC(=O)CN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21.N>>NC(=O)CN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
C(=O)(OC)CN1C(=O)[C@H](CC2=CC=CC=C12)NC(=O)C=1NC2=CC=C(C=C2C1)Cl.N>>NC(=O)CN1C(=O)[C@H](CC2=CC=CC=C12)NC(=O)C=1NC2=CC=C(C=C2C1)Cl
CO[C:2](=[O:3])[CH2:4][N:5]1[C:6](=[O:7])[C@@H:8]([NH:9][C:10](=[O:11])[c:12]2[cH:13][c:14]3[cH:15][c:16]([Cl:17])[cH:18][cH:19][c:20]3[nH:21]2)[CH2:22][c:23]2[cH:24][cH:25][cH:26][cH:27][c:28]21.[NH3:1]>>[NH2:1][C:2](=[O:3])[CH2:4][N:5]1[C:6](=[O:7])[C@@H:8]([NH:9][C:10](=[O:11])[c:12]2[cH:13][c:14]3[cH:15][c:16]([Cl:...
COC(=O)CN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21.N
NC(=O)CN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
null
null
CO.O1CCCC1
Acylation
OtherReaction
d5b10d4f469e7a196a3b04a6a9e159a7d90514b6df5b50c1197d4b1b774c04e1
adc0ef6f6c1340dd2dbab737c85bf17fc842769181c5db1a2b4f82b391b28f9f
O=C(N[C@H]1Cc2ccccc2NC1=O)c1cc2ccccc2[nH]1
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[#7:4]-[C:5]=[O;D1;H0:6].[NH3;D0;+0:7]>>[NH2;D1;+0:7]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[#7:4]-[C:5]=[O;D1;H0:6]
null
[]
null
null
16
HOUR
(S)-1-carbomethoxymethyl-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyril (Example 8) (5 mg) was dissolved in a mixture of tetrahydrofuran (1 mL) and 2 M ammonia in methanol solution (2 mL). After stirring for 16 h at room temperature, the solvent was evaporated and the residue was coevaporated with methanol (...
10.6084/m9.figshare.5104873.v1
null
Ester
Primary amide
null
null
c1ccc2[nH]ccc2c1.c1ccc2c(c1)CCC[NH]2
HO-
CO.O1CCCC1
null
16
COC(=O)CN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21.N>CO.O1CCCC1>NC(=O)CN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-7ac6fa017fd64b0fbef0e360df747472
CN1C(=O)[C@H](NC(=O)OC(C)(C)C)Cc2ccccc21>>CN1C(=O)[C@H](N)Cc2ccccc21
C(C)(C)(C)OC(=O)N[C@H]1C(N(C2=CC=CC=C2C1)C)=O.Cl>>Cl.N[C@H]1C(N(C2=CC=CC=C2C1)C)=O
CC(C)(C)OC(=O)[NH:6][C@H:5]1[C:3](=[O:4])[N:2]([CH3:1])[c:13]2[c:8]([cH:9][cH:10][cH:11][cH:12]2)[CH2:7]1>>[CH3:1][N:2]1[C:3](=[O:4])[C@H:5]([NH2:6])[CH2:7][c:8]2[cH:9][cH:10][cH:11][cH:12][c:13]21
CN1C(=O)[C@H](NC(=O)OC(C)(C)C)Cc2ccccc21
CN1C(=O)[C@H](N)Cc2ccccc21
null
null
O1CCOCC1
Reduction
Hydrogenolysis of amides/imides/carbamates
3c33dd2a2d355ee5ba0287367e209aa147a39aa00607f0c95fb2bf1ade45d014
c5b5dffe7dd8beebdc1baa8b5b05300a9f7079e65dcfd42ade6f8a77ff09537d
O=C1CCc2ccccc2N1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2](-[C:3])-[C:4](=[O;D1;H0:5])-[#7:6](-[C;D1;H3:7])-[c:8]>>[C:3]-[C:2](-[NH2;D1;+0:1])-[C:4](=[O;D1;H0:5])-[#7:6](-[C;D1;H3:7])-[c:8]
null
[]
null
null
null
null
(R)-3-t-butyloxycarbonylamino-1-methyl-3,4-dihydrocarbostyril (20 mg) was dissolved in 4 M hydrogen chloride in 1,4-dioxane solution (5 mL) at room temperature. After 1 h the solvent was evaporated under vacuum, and the residue was twice taken up in toluene (5 mL) and evaporated under vacuum to provide (R)-3-amino-1-me...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Primary amine
null
null
c1ccc2c(c1)CCC[NH]2
HO-
O1CCOCC1
null
null
CN1C(=O)[C@H](NC(=O)OC(C)(C)C)Cc2ccccc21>O1CCOCC1>CN1C(=O)[C@H](N)Cc2ccccc21
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-f9013a076f6747788b58534bb7b45797
CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21>>CN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@H]1C(N(C2=CC=CC=C2C1)C)=O.C(C)(C)(C)OC(=O)N[C@H]1C(NC2=CC=CC=C2C1)=O.ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@H]1C(NC2=CC=CC=C2C1)=O>>ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@@H]1C(N(C2=CC=CC=C2C1)C)=O
[CH3:1][N:2]1[C:3](=[O:4])[C@H:5]([NH:6][C:7](=[O:8])[c:9]2[cH:10][c:11]3[cH:12][c:13]([Cl:14])[cH:15][cH:16][c:17]3[nH:18]2)[CH2:19][c:20]2[cH:21][cH:22][cH:23][cH:24][c:25]21>>[CH3:1][N:2]1[C:3](=[O:4])[C@@H:5]([NH:6][C:7](=[O:8])[c:9]2[cH:10][c:11]3[cH:12][c:13]([Cl:14])[cH:15][cH:16][c:17]3[nH:18]2)[CH2:19][c:20]2[...
CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
CN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
null
null
null
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
O=C(N[C@H]1Cc2ccccc2NC1=O)c1cc2ccccc2[nH]1
null
null
[]
null
null
null
null
The title compound was prepared from (S)-3-t-butyloxycarbonylamino-3,4-dihydrocarbostyril (prepared in Example 5) by the procedures described for the preparation of (R)-3-(5-chloroindole-2-carbonylamino)-1-methyl-3,4-dihydrocarbostyril (Example 14) from (R)-3-t-butyloxycarbonylamino-3,4-dihydrocarbostyril. HPLC/MS [M+H...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
c1ccc2[nH]ccc2c1.c1ccc2c(c1)CCC[NH]2
null
null
null
null
CN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21>>CN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-5adcca477c254be6a192106fe55a0014
C=CCN1C(=O)[C@@H](NC(=O)OC(C)(C)C)Cc2ccccc21>>C=CCN1C(=O)[C@@H](N)Cc2ccccc21
C(C=C)N1C(=O)[C@H](CC2=CC=CC=C12)NC(=O)OC(C)(C)C.Cl>>Cl.C(C=C)N1C(=O)[C@H](CC2=CC=CC=C12)N
CC(C)(C)OC(=O)[NH:8][C@@H:7]1[C:5](=[O:6])[N:4]([CH2:3][CH:2]=[CH2:1])[c:15]2[c:10]([cH:11][cH:12][cH:13][cH:14]2)[CH2:9]1>>[CH2:1]=[CH:2][CH2:3][N:4]1[C:5](=[O:6])[C@@H:7]([NH2:8])[CH2:9][c:10]2[cH:11][cH:12][cH:13][cH:14][c:15]21
C=CCN1C(=O)[C@@H](NC(=O)OC(C)(C)C)Cc2ccccc21
C=CCN1C(=O)[C@@H](N)Cc2ccccc21
null
null
O1CCOCC1
Reduction
Hydrogenolysis of amides/imides/carbamates
3c33dd2a2d355ee5ba0287367e209aa147a39aa00607f0c95fb2bf1ade45d014
c5b5dffe7dd8beebdc1baa8b5b05300a9f7079e65dcfd42ade6f8a77ff09537d
O=C1CCc2ccccc2N1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2](-[C:3])-[C:4](=[O;D1;H0:5])-[#7:6](-[C:7]-[C:8]=[C;D1;H2:9])-[c:10]>>[C:3]-[C:2](-[NH2;D1;+0:1])-[C:4](=[O;D1;H0:5])-[#7:6](-[C:7]-[C:8]=[C;D1;H2:9])-[c:10]
null
[]
null
null
null
null
(S)-1-allyl-3-t-butyloxycarbonylamino-3,4-dihydrocarbostyril (9.7 mg) was dissolved in 4 M hydrogen chloride in 1,4-dioxane solution (2 mL) at room temperature, and a white precipitate soon formed. After 30 min the solvent was evaporated under vacuum, and the residue was twice taken up in toluene (5 mL) and evaporated ...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Primary amine
null
null
c1ccc2c(c1)CCC[NH]2
HO-
O1CCOCC1
null
null
C=CCN1C(=O)[C@@H](NC(=O)OC(C)(C)C)Cc2ccccc21>O1CCOCC1>C=CCN1C(=O)[C@@H](N)Cc2ccccc21
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-516d5b56df98453cafe3dd8cb1f58999
C=CCN1C(=O)[C@@H](N)Cc2ccccc21.O=C(O)c1cc2cc(Cl)ccc2[nH]1>>C=CCN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
Cl.C(C=C)N1C(=O)[C@H](CC2=CC=CC=C12)N.ClC=1C=C2C=C(NC2=CC1)C(=O)O.ON1N=NC2=C1N=CC=C2.Cl.CN(CCCN=C=NCC)C.C(C)(C)N(CC)C(C)C>>C(C=C)N1C(=O)[C@H](CC2=CC=CC=C12)NC(=O)C=1NC2=CC=C(C=C2C1)Cl
[CH2:1]=[CH:2][CH2:3][N:4]1[C:5](=[O:6])[C@@H:7]([NH2:8])[CH2:21][c:22]2[cH:23][cH:24][cH:25][cH:26][c:27]21.O[C:9](=[O:10])[c:11]1[cH:12][c:13]2[cH:14][c:15]([Cl:16])[cH:17][cH:18][c:19]2[nH:20]1>>[CH2:1]=[CH:2][CH2:3][N:4]1[C:5](=[O:6])[C@@H:7]([NH:8][C:9](=[O:10])[c:11]2[cH:12][c:13]3[cH:14][c:15]([Cl:16])[cH:17][cH...
C=CCN1C(=O)[C@@H](N)Cc2ccccc21.O=C(O)c1cc2cc(Cl)ccc2[nH]1
C=CCN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
null
null
O1CCCC1
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(N[C@H]1Cc2ccccc2NC1=O)c1cc2ccccc2[nH]1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6].[C:7]-[C:8](-[NH2;D1;+0:9])-[C:10](=[O;D1;H0:11])-[#7:12](-[C:13]-[C:14]=[C;D1;H2:15])-[c:16]>>[C:7]-[C:8](-[NH;D2;+0:9]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6])-[C:10](=[O;D1;H0:11])-[#7:12](-[C:13]-[C:14]=[C;D1;H2:15])-[c:16]
53.7
[{"value": 53.7, "product": "C(C=C)N1C(=O)[C@H](CC2=CC=CC=C12)NC(=O)C=1NC2=CC=C(C=C2C1)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
(S)-1-allyl-3-amino-3,4-dihydrocarbostyril hydrochloride (7.6 mg) was added to a mixture of tetrahydrofuran (4 mL), 5-chloroindole-2-carboxylic acid (6.9 mg), 1-hydroxy-7-azabenzotriazole (5.5 mg), and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (7.7 mg) at room temperature. Diisopropylethylamine (12 ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccc2[nH]ccc2c1.c1ccc2c(c1)CCC[NH]2
HO-
O1CCCC1
null
16
C=CCN1C(=O)[C@@H](N)Cc2ccccc21.O=C(O)c1cc2cc(Cl)ccc2[nH]1>O1CCCC1>C=CCN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-79c37683c1aa4634b0c0d6974cfb87dd
N#CCBr.O=C(N[C@H]1Cc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1>>N#CCN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
Cl.C[O-].[Na+].ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@@H]1C(NC2=CC=CC=C2C1)=O.BrCC#N>>ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@@H]1C(N(C2=CC=CC=C2C1)CC#N)=O
Br[CH2:3][C:2]#[N:1].[NH:4]1[C:5](=[O:6])[C@@H:7]([NH:8][C:9](=[O:10])[c:11]2[cH:12][c:13]3[cH:14][c:15]([Cl:16])[cH:17][cH:18][c:19]3[nH:20]2)[CH2:21][c:22]2[cH:23][cH:24][cH:25][cH:26][c:27]21>>[N:1]#[C:2][CH2:3][N:4]1[C:5](=[O:6])[C@@H:7]([NH:8][C:9](=[O:10])[c:11]2[cH:12][c:13]3[cH:14][c:15]([Cl:16])[cH:17][cH:18][...
N#CCBr.O=C(N[C@H]1Cc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1
N#CCN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
null
null
O.C(C)(=O)OCC.O1CCCC1
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
e7b4b186b3651fd15b60671427dc34c5cd6cb02aa0116a7c1fd6c1cf6f406256
4a6c1e88c9e8bed487b746792f88d478ff36cc235f9a217d4632e6babdebdc9a
O=C(N[C@H]1Cc2ccccc2NC1=O)c1cc2ccccc2[nH]1
Br-[CH2;D2;+0:1]-[C:2]#[N;D1;H0:3].[C:4]-[C:5](=[O;D1;H0:6])-[NH;D2;+0:7]-[c:8](:[c:9]):[c:10]>>[C:4]-[C:5](=[O;D1;H0:6])-[N;H0;D3;+0:7](-[CH2;D2;+0:1]-[C:2]#[N;D1;H0:3])-[c:8](:[c:9]):[c:10]
26.8
[{"value": 26.8, "product": "ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@@H]1C(N(C2=CC=CC=C2C1)CC#N)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
(S)-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyril (Example 4, 13.4 mg) was dissolved in tetrahydrofuran (5 mL) at room temperature under argon with stirring. After cooing to 0° C., sodium methoxide (4.3 mg) was added, followed 2 h later by bromoacetonitrile (7.2 mg). This was warmed to room temperature over...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amide
Tertiary amide
c1ccc2c(c1)CCCN2
c1ccc2c(c1)CCC[NH]2
c1ccc2[nH]ccc2c1.c1ccc2c(c1)CCC[NH]2
HBr
O.C(C)(=O)OCC.O1CCCC1
null
null
N#CCBr.O=C(N[C@H]1Cc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1>O.C(C)(=O)OCC.O1CCCC1>N#CCN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-b00a7ed4fdea484c9fcb5f3121dbfe6d
N#CCN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21>>N#CCN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@@H]1C(N(C2=CC=CC=C2C1)CC#N)=O.ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@@H]1C(NC2=CC=CC=C2C1)=O.ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@H]1C(NC2=CC=CC=C2C1)=O>>ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@H]1C(N(C2=CC=CC=C2C1)CC#N)=O
[N:1]#[C:2][CH2:3][N:4]1[C:5](=[O:6])[C@@H:7]([NH:8][C:9](=[O:10])[c:11]2[cH:12][c:13]3[cH:14][c:15]([Cl:16])[cH:17][cH:18][c:19]3[nH:20]2)[CH2:21][c:22]2[cH:23][cH:24][cH:25][cH:26][c:27]21>>[N:1]#[C:2][CH2:3][N:4]1[C:5](=[O:6])[C@H:7]([NH:8][C:9](=[O:10])[c:11]2[cH:12][c:13]3[cH:14][c:15]([Cl:16])[cH:17][cH:18][c:19]...
N#CCN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
N#CCN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
null
null
null
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
O=C(N[C@@H]1Cc2ccccc2NC1=O)c1cc2ccccc2[nH]1
null
null
[]
null
null
null
null
The title compound was prepared from (R)-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyril (Example 3) by the procedures described for the preparation of (S)-3-(5-chloroindole-2-carbonylamino)-1-cyanomethyl-3,4-dihydrocarbostyril (Example 17) from (S)-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyril. H...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
c1ccc2[nH]ccc2c1.c1ccc2c(c1)CCC[NH]2
null
null
null
null
N#CCN1C(=O)[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21>>N#CCN1C(=O)[C@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)Cc2ccccc21
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-d639b90ca6dd451282aa8ebb8b743be1
N[C@H]1COc2ccccc2NC1=O.O=C(O)c1cc2cc(Cl)ccc2[nH]1>>O=C(N[C@H]1COc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1
Cl.N[C@H]1COC2=C(NC1=O)C=CC=C2.ClC=1C=C2C=C(NC2=CC1)C(=O)O.ON1N=NC2=C1N=CC=C2.Cl.CN(CCCN=C=NCC)C.C(C)(C)N(CC)C(C)C>>ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@H]1COC2=C(NC1=O)C=CC=C2
[NH2:3][C@H:4]1[CH2:5][O:6][c:7]2[cH:8][cH:9][cH:10][cH:11][c:12]2[NH:13][C:14]1=[O:15].O[C:2](=[O:1])[c:16]1[cH:17][c:18]2[cH:19][c:20]([Cl:21])[cH:22][cH:23][c:24]2[nH:25]1>>[O:1]=[C:2]([NH:3][C@H:4]1[CH2:5][O:6][c:7]2[cH:8][cH:9][cH:10][cH:11][c:12]2[NH:13][C:14]1=[O:15])[c:16]1[cH:17][c:18]2[cH:19][c:20]([Cl:21])[c...
N[C@H]1COc2ccccc2NC1=O.O=C(O)c1cc2cc(Cl)ccc2[nH]1
O=C(N[C@H]1COc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1
null
null
O1CCCC1
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(N[C@H]1COc2ccccc2NC1=O)c1cc2ccccc2[nH]1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6].[#8:7]-[C:8]-[C:9](-[NH2;D1;+0:10])-[C:11](=[O;D1;H0:12])-[#7:13]-[c:14]>>[#8:7]-[C:8]-[C:9](-[NH;D2;+0:10]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6])-[C:11](=[O;D1;H0:12])-[#7:13]-[c:14]
88.8
[{"value": 88.8, "product": "ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@H]1COC2=C(NC1=O)C=CC=C2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Alternatively, to a mixture of (S)-3-amino-2,3-dihydro-1,5-benzoxazepin-4(5H)-one hydrochloride salt (54 mg) (prepared in Itoh, et al., Chem. Pharm. Bull. 1986, 34, 1128–1147), tetrahydrofuran (10 mL), 5-chloroindole-2-carboxylic acid (39 mg), 1-hydroxy-7-azabenzotriazole (31 mg), and 1-[3-(dimethylamino)propyl]-3-ethy...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccc2c(c1)NCCCO2.c1ccc2[nH]ccc2c1
HO-
O1CCCC1
null
null
N[C@H]1COc2ccccc2NC1=O.O=C(O)c1cc2cc(Cl)ccc2[nH]1>O1CCCC1>O=C(N[C@H]1COc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-7c264e9779284e15bdd86025c4faf7dd
N[C@H]1COc2ccccc2NC1=O>>N[C@@H]1COc2ccccc2NC1=O
Cl.N[C@H]1COC2=C(NC1=O)C=CC=C2.C(C)(C)(C)OC(=O)N[C@@H](CO)C(=O)O.C(C)(C)(C)OC(=O)N[C@H](CO)C(=O)O>>Cl.N[C@@H]1COC2=C(NC1=O)C=CC=C2
[NH2:2][C@H:3]1[CH2:4][O:5][c:6]2[cH:7][cH:8][cH:9][cH:10][c:11]2[NH:12][C:13]1=[O:14]>>[NH2:2][C@@H:3]1[CH2:4][O:5][c:6]2[cH:7][cH:8][cH:9][cH:10][c:11]2[NH:12][C:13]1=[O:14]
N[C@H]1COc2ccccc2NC1=O
N[C@@H]1COc2ccccc2NC1=O
null
null
null
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
O=C1CCOc2ccccc2N1
null
null
[]
null
null
null
null
(R)-3-amino-2,3-dihydro-1,5-benzoxazepin-4(5H)-one hydrochloride salt was prepared from N-t-butyloxycarbonyl-D-serine by the procedures described in Itoh, et al., Chem. Pharm. Bull. 1986, 34, 1128–1147 for the preparation of (S)-3-amino-2,3-dihydro-1,5-benzoxazepin-4(5H)-one hydrochloride salt from N-t-butyloxycarbonyl...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
c1ccc2c(c1)NCCCO2
null
null
null
null
N[C@H]1COc2ccccc2NC1=O>>N[C@@H]1COc2ccccc2NC1=O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-5487c0c5805446b1b2432f0aff196960
O=C(N[C@H]1COc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1>>O=C(N[C@@H]1COc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1
ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@H]1COC2=C(NC1=O)C=CC=C2.Cl.N[C@H]1COC2=C(NC1=O)C=CC=C2.Cl.N[C@@H]1COC2=C(NC1=O)C=CC=C2>>ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@@H]1COC2=C(NC1=O)C=CC=C2
[O:1]=[C:2]([NH:3][C@H:4]1[CH2:5][O:6][c:7]2[cH:8][cH:9][cH:10][cH:11][c:12]2[NH:13][C:14]1=[O:15])[c:16]1[cH:17][c:18]2[cH:19][c:20]([Cl:21])[cH:22][cH:23][c:24]2[nH:25]1>>[O:1]=[C:2]([NH:3][C@@H:4]1[CH2:5][O:6][c:7]2[cH:8][cH:9][cH:10][cH:11][c:12]2[NH:13][C:14]1=[O:15])[c:16]1[cH:17][c:18]2[cH:19][c:20]([Cl:21])[cH:...
O=C(N[C@H]1COc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1
O=C(N[C@@H]1COc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1
null
null
null
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
O=C(N[C@@H]1COc2ccccc2NC1=O)c1cc2ccccc2[nH]1
null
null
[]
null
null
null
null
The title compound was prepared from (R)-3-amino-2,3-dihydro-1,5-benzoxazepin-4(5H)-one hydrochloride salt by the procedures described for the preparation of (S)-3-(5-chloroindole-2-carbonylamino)-2,3-dihydro-1,5-benzoxazepin-4(5H)-one (Example 20) from (S)-3-amino-2,3-dihydro-1,5-benzoxazepin-4(5H)-one hydrochloride s...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
c1ccc2c(c1)NCCCO2.c1ccc2[nH]ccc2c1
null
null
null
null
O=C(N[C@H]1COc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1>>O=C(N[C@@H]1COc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-bce1a18b501744319de4def70546e546
C[C@@H]1Oc2ccccc2NC(=O)[C@H]1NC(=O)OC(C)(C)C>>C[C@@H]1Oc2ccccc2NC(=O)[C@H]1N
C(C)(C)(C)OC(=O)N[C@H]1[C@@H](OC2=C(NC1=O)C=CC=C2)C.FC(C(=O)O)(F)F.ClCCl.O1CCCC1>>FC(C(=O)O)(F)F.N[C@H]1[C@@H](OC2=C(NC1=O)C=CC=C2)C
CC(C)(C)OC(=O)[NH:14][C@H:13]1[C@H:2]([CH3:1])[O:3][c:4]2[cH:5][cH:6][cH:7][cH:8][c:9]2[NH:10][C:11]1=[O:12]>>[CH3:1][C@@H:2]1[O:3][c:4]2[cH:5][cH:6][cH:7][cH:8][c:9]2[NH:10][C:11](=[O:12])[C@H:13]1[NH2:14]
C[C@@H]1Oc2ccccc2NC(=O)[C@H]1NC(=O)OC(C)(C)C
C[C@@H]1Oc2ccccc2NC(=O)[C@H]1N
null
null
null
Reduction
Hydrogenolysis of amides/imides/carbamates
3c33dd2a2d355ee5ba0287367e209aa147a39aa00607f0c95fb2bf1ade45d014
c5b5dffe7dd8beebdc1baa8b5b05300a9f7079e65dcfd42ade6f8a77ff09537d
O=C1CCOc2ccccc2N1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2](-[C:3]-[#8:4])-[C:5](=[O;D1;H0:6])-[#7:7]-[c:8]>>[#8:4]-[C:3]-[C:2](-[NH2;D1;+0:1])-[C:5](=[O;D1;H0:6])-[#7:7]-[c:8]
null
[]
null
null
null
null
(2S,3S)-3-amino-2-methyl-2,3-dihydro-1,5-benzoxazepin-4(5H)-one trifluoroacetate salt was prepared from (2S,3S)-3-t-butyloxycarbonylamino-2-methyl-2,3-dihydro-1,5-benzoxazepin-4(5H)-one (Rob, et al., Bioorg. & Med. Chem. Lett. 1994, 4, 1789–1794) by treatment with a solution of trifluoroacetic acid-dichloromethane-tetr...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Primary amine
null
null
c1ccc2c(c1)NCCCO2
HO-
null
null
null
C[C@@H]1Oc2ccccc2NC(=O)[C@H]1NC(=O)OC(C)(C)C>>C[C@@H]1Oc2ccccc2NC(=O)[C@H]1N
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-ef2594d9793d4786b45c3fc9f7b648ba
C[C@@H]1Oc2ccccc2NC(=O)[C@@H]1NC(=O)OC(C)(C)C>>C[C@@H]1Oc2ccccc2NC(=O)[C@@H]1N
C(C)(C)(C)OC(=O)N[C@@H]1[C@@H](OC2=C(NC1=O)C=CC=C2)C.FC(C(=O)O)(F)F.ClCCl.O1CCCC1>>FC(C(=O)O)(F)F.N[C@@H]1[C@@H](OC2=C(NC1=O)C=CC=C2)C
CC(C)(C)OC(=O)[NH:14][C@@H:13]1[C@H:2]([CH3:1])[O:3][c:4]2[cH:5][cH:6][cH:7][cH:8][c:9]2[NH:10][C:11]1=[O:12]>>[CH3:1][C@@H:2]1[O:3][c:4]2[cH:5][cH:6][cH:7][cH:8][c:9]2[NH:10][C:11](=[O:12])[C@@H:13]1[NH2:14]
C[C@@H]1Oc2ccccc2NC(=O)[C@@H]1NC(=O)OC(C)(C)C
C[C@@H]1Oc2ccccc2NC(=O)[C@@H]1N
null
null
null
Reduction
Hydrogenolysis of amides/imides/carbamates
3c33dd2a2d355ee5ba0287367e209aa147a39aa00607f0c95fb2bf1ade45d014
c5b5dffe7dd8beebdc1baa8b5b05300a9f7079e65dcfd42ade6f8a77ff09537d
O=C1CCOc2ccccc2N1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2](-[C:3]-[#8:4])-[C:5](=[O;D1;H0:6])-[#7:7]-[c:8]>>[#8:4]-[C:3]-[C:2](-[NH2;D1;+0:1])-[C:5](=[O;D1;H0:6])-[#7:7]-[c:8]
null
[]
null
null
null
null
(2S,3R)-3-amino-2-methyl-2,3-dihydro-1,5-benzoxazepin-4(5H)-one trifluoroacetate salt was prepared from (2S,3R)-3-t-butyloxycarbonylamino-2-methyl-2,3-dihydro-1,5-benzoxazepin-4(5H)-one (Robl, et al., Bioorg. & Med. Chem. Lett. 1994, 4, 1789–1794) by treatment with a solution of trifluoroacetic acid-dichloromethane-tet...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Primary amine
null
null
c1ccc2c(c1)NCCCO2
HO-
null
null
null
C[C@@H]1Oc2ccccc2NC(=O)[C@@H]1NC(=O)OC(C)(C)C>>C[C@@H]1Oc2ccccc2NC(=O)[C@@H]1N
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-659e4f7223dd4a359a81bd1f34cd5b0f
C[C@@H]1Oc2ccccc2NC(=O)[C@H]1NC(=O)c1cc2cc(Cl)ccc2[nH]1>>C[C@@H]1Oc2ccccc2NC(=O)[C@@H]1NC(=O)c1cc2cc(Cl)ccc2[nH]1
ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@H]1[C@@H](OC2=C(NC1=O)C=CC=C2)C.FC(C(=O)O)(F)F.N[C@H]1[C@@H](OC2=C(NC1=O)C=CC=C2)C.FC(C(=O)O)(F)F.N[C@@H]1[C@@H](OC2=C(NC1=O)C=CC=C2)C>>ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@@H]1[C@@H](OC2=C(NC1=O)C=CC=C2)C
[CH3:1][C@@H:2]1[O:3][c:4]2[cH:5][cH:6][cH:7][cH:8][c:9]2[NH:10][C:11](=[O:12])[C@H:13]1[NH:14][C:15](=[O:16])[c:17]1[cH:18][c:19]2[cH:20][c:21]([Cl:22])[cH:23][cH:24][c:25]2[nH:26]1>>[CH3:1][C@@H:2]1[O:3][c:4]2[cH:5][cH:6][cH:7][cH:8][c:9]2[NH:10][C:11](=[O:12])[C@@H:13]1[NH:14][C:15](=[O:16])[c:17]1[cH:18][c:19]2[cH:...
C[C@@H]1Oc2ccccc2NC(=O)[C@H]1NC(=O)c1cc2cc(Cl)ccc2[nH]1
C[C@@H]1Oc2ccccc2NC(=O)[C@@H]1NC(=O)c1cc2cc(Cl)ccc2[nH]1
null
null
null
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
O=C(N[C@@H]1COc2ccccc2NC1=O)c1cc2ccccc2[nH]1
null
null
[]
null
null
null
null
The title compound was prepared from (2S,3R)-3-amino-2-methyl-2,3-dihydro-1,5-benzoxazepin-4(5H)-one trifluoroacetate salt by the procedures described for the preparation of (2S,3S)-3-(5-chloroindole-2-carbonylamino)-2-methyl-2,3-dihydro-1,5-benzoxazepin-4(5H)-one (Example 22) from (2S,3S)-3-amino-2-methyl-2,3-dihydro-...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
c1ccc2c(c1)NCCCO2.c1ccc2[nH]ccc2c1
null
null
null
null
C[C@@H]1Oc2ccccc2NC(=O)[C@H]1NC(=O)c1cc2cc(Cl)ccc2[nH]1>>C[C@@H]1Oc2ccccc2NC(=O)[C@@H]1NC(=O)c1cc2cc(Cl)ccc2[nH]1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-d4ab1160d8704717bff53901854961c7
N[C@@H]1Cc2ccccc2CNC1=O.O=C(O)c1cc2cc(Cl)ccc2[nH]1>>O=C(N[C@@H]1Cc2ccccc2CNC1=O)c1cc2cc(Cl)ccc2[nH]1
C(C)(C)N(CC)C(C)C.ClC=1C=C2C=C(NC2=CC1)C(=O)O.ON1N=NC2=C1N=CC=C2.Cl.CN(CCCN=C=NCC)C.Cl.N[C@H]1C(NCC2=C(C1)C=CC=C2)=O>>ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@H]1C(NCC2=C(C1)C=CC=C2)=O
[NH2:3][C@@H:4]1[CH2:5][c:6]2[cH:7][cH:8][cH:9][cH:10][c:11]2[CH2:12][NH:13][C:14]1=[O:15].O[C:2](=[O:1])[c:16]1[cH:17][c:18]2[cH:19][c:20]([Cl:21])[cH:22][cH:23][c:24]2[nH:25]1>>[O:1]=[C:2]([NH:3][C@@H:4]1[CH2:5][c:6]2[cH:7][cH:8][cH:9][cH:10][c:11]2[CH2:12][NH:13][C:14]1=[O:15])[c:16]1[cH:17][c:18]2[cH:19][c:20]([Cl:...
N[C@@H]1Cc2ccccc2CNC1=O.O=C(O)c1cc2cc(Cl)ccc2[nH]1
O=C(N[C@@H]1Cc2ccccc2CNC1=O)c1cc2cc(Cl)ccc2[nH]1
null
null
O1CCCC1
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(N[C@@H]1Cc2ccccc2CNC1=O)c1cc2ccccc2[nH]1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6].[C:7]-[#7:8]-[C:9](=[O;D1;H0:10])-[C:11](-[NH2;D1;+0:12])-[C:13]>>[C:7]-[#7:8]-[C:9](=[O;D1;H0:10])-[C:11](-[NH;D2;+0:12]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6])-[C:13]
44
[{"value": 44.0, "product": "ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@H]1C(NCC2=C(C1)C=CC=C2)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
(R)-4-amino-2, 3,4,5-tetrahydro-2-benzazepin-3 (1H)-one hydrochloride salt (387 mg) (amine free base prepared in U.S. Pat. No. 5,545,735) was added to a mixture of tetrahydrofuran (40 mL), 5-chloroindole-2-carboxylic acid (356 mg), 1-hydroxy-7-azabenzotriazole (272 mg), and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimi...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccc2c(c1)CCCNC2.c1ccc2[nH]ccc2c1
HO-
O1CCCC1
null
16
N[C@@H]1Cc2ccccc2CNC1=O.O=C(O)c1cc2cc(Cl)ccc2[nH]1>O1CCCC1>O=C(N[C@@H]1Cc2ccccc2CNC1=O)c1cc2cc(Cl)ccc2[nH]1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-94d114d92fa5432ab753cd58d55d0023
C[C@@H](C(=O)O)N(C(=O)OC(C)(C)C)c1ccccc1C#N>>C[C@@H](C(=O)O)N(C(=O)OC(C)(C)C)c1ccccc1CN
C(C)(C)(C)OC(=O)N([C@@H](C)C(=O)O)C1=C(C=CC=C1)C#N>>C(C)(C)(C)OC(=O)N([C@@H](C)C(=O)O)C1=C(C=CC=C1)CN
[CH3:1][C@@H:2]([C:3](=[O:4])[OH:5])[N:6]([C:7](=[O:8])[O:9][C:10]([CH3:11])([CH3:12])[CH3:13])[c:14]1[cH:15][cH:16][cH:17][cH:18][c:19]1[C:20]#[N:21]>>[CH3:1][C@@H:2]([C:3](=[O:4])[OH:5])[N:6]([C:7](=[O:8])[O:9][C:10]([CH3:11])([CH3:12])[CH3:13])[c:14]1[cH:15][cH:16][cH:17][cH:18][c:19]1[CH2:20][NH2:21]
C[C@@H](C(=O)O)N(C(=O)OC(C)(C)C)c1ccccc1C#N
C[C@@H](C(=O)O)N(C(=O)OC(C)(C)C)c1ccccc1CN
null
[Ni]
CO
Reduction
Reduction of nitrile to amine
65bec2d9f430701d30dc9fcbe1c5418f3dfa174d67be035c50edfc71895dc9c7
e8d1bc928b94bd4f5bf4b23363ce8f88b1ce7d146ba93829e7b8ad8dbe0007a7
c1ccccc1
[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]
40
[{"value": 40.0, "product": "C(C)(C)(C)OC(=O)N([C@@H](C)C(=O)O)C1=C(C=CC=C1)CN", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
60
HOUR
A mixture of (S)—N-t-butyloxycarbonyl(2-cyanophenyl)alanine (1.0 g), Raney® Nickel (1.0 g), and methanol (20 mL) was hydrogenated in a Parr apparatus at 50 psi for 60 h at room temperature. The catalyst was filtered and rinsed with methanol (20 mL three times). The combined filtrate and rinses were evaporated under vac...
10.6084/m9.figshare.5104873.v1
null
Nitrile
Primary amine
null
null
c1ccccc1
null
[Ni].CO
null
60
C[C@@H](C(=O)O)N(C(=O)OC(C)(C)C)c1ccccc1C#N>[Ni].CO>C[C@@H](C(=O)O)N(C(=O)OC(C)(C)C)c1ccccc1CN
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-ca029937102741169ab21ba3db64bf5e
C[C@@H](C(=O)O)N(C(=O)OC(C)(C)C)c1ccccc1CN>>CC(C)(C)OC(=O)N[C@H]1Cc2ccccc2CNC1=O
C(C)(C)(C)OC(=O)N([C@@H](C)C(=O)O)C1=C(C=CC=C1)CN.CN(C=O)C.ON1N=NC2=C1N=CC=C2.Cl.CN(CCCN=C=NCC)C>>C(C)(C)(C)OC(=O)N[C@@H]1C(NCC2=C(C1)C=CC=C2)=O
O[C:19]([C@@H:9]([N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[c:11]1[cH:12][cH:13][cH:14][cH:15][c:16]1[CH2:17][NH2:18])[CH3:10])=[O:20]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][C@H:9]1[CH2:10][c:11]2[cH:12][cH:13][cH:14][cH:15][c:16]2[CH2:17][NH:18][C:19]1=[O:20]
C[C@@H](C(=O)O)N(C(=O)OC(C)(C)C)c1ccccc1CN
CC(C)(C)OC(=O)N[C@H]1Cc2ccccc2CNC1=O
null
null
ClCCl
Functional Group Interconversion
OtherReaction
5d30c0390c44183b097b5657eb2c4ee943c1eb6c4c46da809f138024ee5031ac
0db3a89fcba8d0e75060638a126c5d84ec832d585668e18e59a622c723c2f731
O=C1CCc2ccccc2CN1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[CH3;D1;+0:4])-[N;H0;D3;+0:5](-[C:6](=[O;D1;H0:7])-[#8:8]-[C:9](-[C;D1;H3:10])(-[C;D1;H3:11])-[C;D1;H3:12])-[c;H0;D3;+0:13](:[c:14]:[c:15]):[c:16](-[C:17]-[NH2;D1;+0:18]):[c:19]>>[C;D1;H3:10]-[C:9](-[C;D1;H3:11])(-[C;D1;H3:12])-[#8:8]-[C:6](=[O;D1;H0:7])-[NH;D2;+0:5]-[C:3]1-[CH2;D2...
null
[]
null
null
1
HOUR
A mixture of (S)—N-t-butyloxycarbonyl(2-aminomethylphenyl)alanine (353 mg), N,N-dimethylformamide (10 mL), dichloromethane (50 mL), 1-hydroxy-7-azabenzotriazole (252 mg), and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (180 mg) was stirred at room temperature for 1 h. The solvent was removed under vac...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Carboxylic acid.Primary amine
Carbamic ester.Secondary amide
c1ccccc1
c1ccc2c(c1)CCCNC2
c1ccc2c(c1)CCCNC2
HO-
ClCCl
null
1
C[C@@H](C(=O)O)N(C(=O)OC(C)(C)C)c1ccccc1CN>ClCCl>CC(C)(C)OC(=O)N[C@H]1Cc2ccccc2CNC1=O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-da942735b7e648a3ac69568f23773259
CC(C)(C)OC(=O)N[C@H]1Cc2ccccc2CNC1=O>>N[C@H]1Cc2ccccc2CNC1=O
C(C)(C)(C)OC(=O)N[C@@H]1C(NCC2=C(C1)C=CC=C2)=O.Cl>>Cl.N[C@@H]1C(NCC2=C(C1)C=CC=C2)=O
CC(C)(C)OC(=O)[NH:2][C@H:3]1[CH2:4][c:5]2[cH:6][cH:7][cH:8][cH:9][c:10]2[CH2:11][NH:12][C:13]1=[O:14]>>[NH2:2][C@H:3]1[CH2:4][c:5]2[cH:6][cH:7][cH:8][cH:9][c:10]2[CH2:11][NH:12][C:13]1=[O:14]
CC(C)(C)OC(=O)N[C@H]1Cc2ccccc2CNC1=O
N[C@H]1Cc2ccccc2CNC1=O
null
null
C(C)OCC
Reduction
Hydrogenolysis of amides/imides/carbamates
3c33dd2a2d355ee5ba0287367e209aa147a39aa00607f0c95fb2bf1ade45d014
c5b5dffe7dd8beebdc1baa8b5b05300a9f7079e65dcfd42ade6f8a77ff09537d
O=C1CCc2ccccc2CN1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2](-[C:3])-[C:4](=[O;D1;H0:5])-[#7:6]-[C:7]>>[C:7]-[#7:6]-[C:4](=[O;D1;H0:5])-[C:2](-[NH2;D1;+0:1])-[C:3]
null
[]
null
null
16
HOUR
(S)-4-(t-butyloxycarbonylamino)-2,3,4,5-tetrahydro-2-benzazepin-3(1H)-one (276 mg) was dissolved in 2 M hydrogen chloride in diethyl ether solution (25 mL) at room temperature. A precipitate slowly formed. After 16 h stirring the solvent was evaporated under vacuum. The residue was twice taken up in toluene (10 mL) and...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Primary amine
null
null
c1ccc2c(c1)CCCNC2
HO-
C(C)OCC
null
16
CC(C)(C)OC(=O)N[C@H]1Cc2ccccc2CNC1=O>C(C)OCC>N[C@H]1Cc2ccccc2CNC1=O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-3f80ff37dc2a4555bcb5ef06034a0b77
N[C@H]1Cc2ccccc2CNC1=O.O=C(O)c1cc2cc(Cl)ccc2[nH]1>>O=C(N[C@H]1Cc2ccccc2CNC1=O)c1cc2cc(Cl)ccc2[nH]1
Cl.N[C@@H]1C(NCC2=C(C1)C=CC=C2)=O.ClC=1C=C2C=C(NC2=CC1)C(=O)O.ON1N=NC2=C1N=CC=C2.Cl.CN(CCCN=C=NCC)C.C(C)(C)N(CC)C(C)C>>ClC=1C=C2C=C(NC2=CC1)C(=O)N[C@@H]1C(NCC2=C(C1)C=CC=C2)=O
[NH2:3][C@H:4]1[CH2:5][c:6]2[cH:7][cH:8][cH:9][cH:10][c:11]2[CH2:12][NH:13][C:14]1=[O:15].O[C:2](=[O:1])[c:16]1[cH:17][c:18]2[cH:19][c:20]([Cl:21])[cH:22][cH:23][c:24]2[nH:25]1>>[O:1]=[C:2]([NH:3][C@H:4]1[CH2:5][c:6]2[cH:7][cH:8][cH:9][cH:10][c:11]2[CH2:12][NH:13][C:14]1=[O:15])[c:16]1[cH:17][c:18]2[cH:19][c:20]([Cl:21...
N[C@H]1Cc2ccccc2CNC1=O.O=C(O)c1cc2cc(Cl)ccc2[nH]1
O=C(N[C@H]1Cc2ccccc2CNC1=O)c1cc2cc(Cl)ccc2[nH]1
null
null
O1CCCC1
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(N[C@H]1Cc2ccccc2CNC1=O)c1cc2ccccc2[nH]1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6].[C:7]-[#7:8]-[C:9](=[O;D1;H0:10])-[C:11](-[NH2;D1;+0:12])-[C:13]>>[C:7]-[#7:8]-[C:9](=[O;D1;H0:10])-[C:11](-[NH;D2;+0:12]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6])-[C:13]
null
[]
null
null
null
null
A mixture of (S)-4-amino-2,3,4,5-tetrahydro-2-benzazepin-3(1H)-one hydrochloride (all of that prepared above), tetrahydrofuran (25 mL), 5-chloroindole-2-carboxylic acid (198 mg), 1-hydroxy-7-azabenzotriazole (150 mg), and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (210 mg) was stirred at room tempera...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccc2c(c1)CCCNC2.c1ccc2[nH]ccc2c1
HO-
O1CCCC1
null
null
N[C@H]1Cc2ccccc2CNC1=O.O=C(O)c1cc2cc(Cl)ccc2[nH]1>O1CCCC1>O=C(N[C@H]1Cc2ccccc2CNC1=O)c1cc2cc(Cl)ccc2[nH]1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-0855fb1c75354af99d14871d375e7943
CC(C)(C)OC(=O)N[C@@H](CO)C(=O)O.O=[N+]([O-])c1cccnc1Cl>>CC(C)(C)OC(=O)N[C@@H](COc1ncccc1[N+](=O)[O-])C(=O)O
O.C(C)(C)(C)OC(=O)N[C@@H](CO)C(=O)O.[H-].[Na+].ClC1=NC=CC=C1[N+](=O)[O-]>>C(C)(C)(C)OC(=O)N[C@@H](COC1=NC=CC=C1[N+](=O)[O-])C(=O)O
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][C@@H:9]([CH2:10][OH:11])[C:21](=[O:22])[OH:23].Cl[c:12]1[n:13][cH:14][cH:15][cH:16][c:17]1[N+:18](=[O:19])[O-:20]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][C@@H:9]([CH2:10][O:11][c:12]1[n:13][cH:14][cH:15][cH:16][c:17]1[N+:18](=[O:19])[O-:20])[C:21](=...
CC(C)(C)OC(=O)N[C@@H](CO)C(=O)O.O=[N+]([O-])c1cccnc1Cl
CC(C)(C)OC(=O)N[C@@H](COc1ncccc1[N+](=O)[O-])C(=O)O
null
null
CN(C=O)C
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
ea617b323b892eda23f5ae30e789991ea9692064ef355a16e8ed81c16e743d2b
a4cafa7bcd156e21cca6eaac1b32e28ec8540642a31181122e6957f3d7559631
c1ccncc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](-[#7;+:5]):[c:6].[O;D1;H0:7]=[C:8](-[O;D1;H1:9])-[C:10]-[C:11]-[OH;D1;+0:12]>>[#7;+:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[O;H0;D2;+0:12]-[C:11]-[C:10]-[C:8](=[O;D1;H0:7])-[O;D1;H1:9]):[#7;a:2]:[c:3]
74.5
[{"value": 74.5, "product": "C(C)(C)(C)OC(=O)N[C@@H](COC1=NC=CC=C1[N+](=O)[O-])C(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
1
HOUR
To a stirring solution of N-t-butyloxycarbonyl-L-serine (2.26 g) in N,N-dimethylformamide (15 mL) under argon at −20° C. was slowly added sodium hydride (60% oil dispersion, 0.88 g gross weight). The resulting mixture was warmed to 0° C. for 1 h, then recooled to −20° C. before a solution of 2-chloro-3-nitropyridine (1...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol
Ether
c1ccncc1
c1ccncc1
c1ccncc1
HCl
CN(C=O)C
0
1
CC(C)(C)OC(=O)N[C@@H](CO)C(=O)O.O=[N+]([O-])c1cccnc1Cl>CN(C=O)C>CC(C)(C)OC(=O)N[C@@H](COc1ncccc1[N+](=O)[O-])C(=O)O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-5b68b01f24c048a9abcf80baf3ff1997
NC1Cc2ccccc2NC1=O.O=C(O)c1cc2ccccc2[nH]1>>O=C(NC1Cc2ccccc2NC1=O)c1cc2ccccc2[nH]1
Cl.NC1C(NC2=CC=CC=C2C1)=O.N1C(=CC2=CC=CC=C12)C(=O)O>>N1C(=CC2=CC=CC=C12)C(=O)NC1C(NC2=CC=CC=C2C1)=O
[NH2:3][CH:4]1[CH2:5][c:6]2[cH:7][cH:8][cH:9][cH:10][c:11]2[NH:12][C:13]1=[O:14].O[C:2](=[O:1])[c:15]1[cH:16][c:17]2[cH:18][cH:19][cH:20][cH:21][c:22]2[nH:23]1>>[O:1]=[C:2]([NH:3][CH:4]1[CH2:5][c:6]2[cH:7][cH:8][cH:9][cH:10][c:11]2[NH:12][C:13]1=[O:14])[c:15]1[cH:16][c:17]2[cH:18][cH:19][cH:20][cH:21][c:22]2[nH:23]1
NC1Cc2ccccc2NC1=O.O=C(O)c1cc2ccccc2[nH]1
O=C(NC1Cc2ccccc2NC1=O)c1cc2ccccc2[nH]1
null
null
null
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(NC1Cc2ccccc2NC1=O)c1cc2ccccc2[nH]1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6].[C:7]-[C:8](-[NH2;D1;+0:9])-[C:10](=[O;D1;H0:11])-[#7:12]-[c:13]>>[C:7]-[C:8](-[NH;D2;+0:9]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6])-[C:10](=[O;D1;H0:11])-[#7:12]-[c:13]
null
[]
null
null
null
null
The title compound was prepared by the methods of Example 5 using 3-amino-3,4-dihydrocarbostyril hydrochloride in place of (R)-3-amino-3,4-dihydrocarbostyril hydrochloride and indole-2-carboxylic acid in place of 5-chloroindole-2-carboxylic acid. HPLC/MS [M+H]+, 306; [M+Na]+, 328. Conditions: See reaction.notes.procedu...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccc2c(c1)CCCN2.c1ccc2[nH]ccc2c1
HO-
null
null
null
NC1Cc2ccccc2NC1=O.O=C(O)c1cc2ccccc2[nH]1>>O=C(NC1Cc2ccccc2NC1=O)c1cc2ccccc2[nH]1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-61481d47f7f540eabd244280fdc4ba8c
COC(=O)C[C@@H]1c2ccccc2NC(=O)[C@H]1N.O=C(O)c1cc2cc(Cl)ccc2[nH]1>>COC(=O)C[C@H]1c2ccccc2NC(=O)[C@@H]1NC(=O)c1cc2cc(Cl)ccc2[nH]1
FC(C(=O)O)(F)F.N[C@@H]1C(NC2=CC=CC=C2[C@H]1CC(=O)OC)=O.Cl.CN(CCCN=C=NCC)C.ON1N=NC2=C1N=CC=C2.ClC=1C=C2C=C(NC2=CC1)C(=O)O.C(C)(C)N(CC)C(C)C>>C(=O)(OC)C[C@@H]1[C@H](C(NC2=CC=CC=C12)=O)NC(=O)C=1NC2=CC=C(C=C2C1)Cl
[CH3:1][O:2][C:3](=[O:4])[CH2:5][C@@H:6]1[c:7]2[cH:8][cH:9][cH:10][cH:11][c:12]2[NH:13][C:14](=[O:15])[C@H:16]1[NH2:17].O[C:18](=[O:19])[c:20]1[cH:21][c:22]2[cH:23][c:24]([Cl:25])[cH:26][cH:27][c:28]2[nH:29]1>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][C@H:6]1[c:7]2[cH:8][cH:9][cH:10][cH:11][c:12]2[NH:13][C:14](=[O:15])[C@@H:16]...
COC(=O)C[C@@H]1c2ccccc2NC(=O)[C@H]1N.O=C(O)c1cc2cc(Cl)ccc2[nH]1
COC(=O)C[C@H]1c2ccccc2NC(=O)[C@@H]1NC(=O)c1cc2cc(Cl)ccc2[nH]1
null
null
CO.O.CN(C=O)C
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(N[C@@H]1Cc2ccccc2NC1=O)c1cc2ccccc2[nH]1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6].[C:7]-[C:8](-[NH2;D1;+0:9])-[C:10](=[O;D1;H0:11])-[#7:12]-[c:13]>>[C:7]-[C:8](-[NH;D2;+0:9]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[#7;a:5]:[c:6])-[C:10](=[O;D1;H0:11])-[#7:12]-[c:13]
56
[{"value": 56.0, "product": "C(=O)(OC)C[C@@H]1[C@H](C(NC2=CC=CC=C12)=O)NC(=O)C=1NC2=CC=C(C=C2C1)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 51.6, "product": "C(=O)(OC)C[C@@H]1[C@H](C(NC2=CC=CC=C12)=O)NC(=O)C=1NC2=CC=C(C=C2C1)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A 1 mL reaction vessel was charged with trans 3-amino-4-carbomethoxymethyl-3,4-dihydrocarbostyril trifluoroacetic acid salt (13 mg, 0.04 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (9 mg, 0.05 mmol), 1-hydroxy-7-azabenzotriazole (7 mg, 0.05 mmol), 5-chloroindole-2-carboxylic acid (8 mg, 0.04 mm...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccc2c(c1)CCCN2.c1ccc2[nH]ccc2c1
HO-
CO.O.CN(C=O)C
null
null
COC(=O)C[C@@H]1c2ccccc2NC(=O)[C@H]1N.O=C(O)c1cc2cc(Cl)ccc2[nH]1>CO.O.CN(C=O)C>COC(=O)C[C@H]1c2ccccc2NC(=O)[C@@H]1NC(=O)c1cc2cc(Cl)ccc2[nH]1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-06705e7a1e0948f294c7e03ad98290a8
COC(=O)[C@H](C)N.O=Cc1ccc(F)cc1>>COC(=O)[C@H](C)NCc1ccc(F)cc1
C(C)(=O)O[BH-](OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+].Cl.COC([C@H](C)N)=O.FC1=CC=C(C=O)C=C1.C(C)N(CC)CC>>COC([C@H](C)NCC1=CC=C(C=C1)F)=O
[CH3:1][O:2][C:3](=[O:4])[C@H:5]([CH3:6])[NH2:7].O=[CH:8][c:9]1[cH:10][cH:11][c:12]([F:13])[cH:14][cH:15]1>>[CH3:1][O:2][C:3](=[O:4])[C@H:5]([CH3:6])[NH:7][CH2:8][c:9]1[cH:10][cH:11][c:12]([F:13])[cH:14][cH:15]1
COC(=O)[C@H](C)N.O=Cc1ccc(F)cc1
COC(=O)[C@H](C)NCc1ccc(F)cc1
null
null
ClCCCl
Heteroatom Alkylation and Arylation
Reductive amination with aldehyde
422be648aea52bce28ccc8fb32ec3178aaa47bbd624f063874619362f075b5f2
7915721a3e395aed85e3c40dc4d725c571a931ac517c6a0da16f2a2b0bb5eac7
c1ccccc1
O=[CH;D2;+0:1]-[c:2](:[c:3]):[c:4].[C;D1;H3:5]-[#8:6]-[C:7](=[O;D1;H0:8])-[C:9](-[C;D1;H3:10])-[NH2;D1;+0:11]>>[C;D1;H3:5]-[#8:6]-[C:7](=[O;D1;H0:8])-[C:9](-[C;D1;H3:10])-[NH;D2;+0:11]-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4]
91
[{"value": 91.0, "product": "COC([C@H](C)NCC1=CC=C(C=C1)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
To a solution of (S)-2-amino-propionic acid methyl ester hydrochloride (25 g, 179 mmol) and 4-fluorobenzaldehyde (23 mL, 215 mmol) in 1,2-dichloroethane (200 mL) was added triethylamine (25 mL, 179 mmol). The resulting mixture was stirred for two hours at ambient temperature followed by addition of sodium triacetoxybor...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Primary amine
Secondary amine
null
null
c1ccccc1
Other
ClCCCl
null
2
COC(=O)[C@H](C)N.O=Cc1ccc(F)cc1>ClCCCl>COC(=O)[C@H](C)NCc1ccc(F)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-c3814d07017d476faad65d26565c6cf8
COC(=O)[C@H](C)NCc1ccc(F)cc1.C[C@@H](NC(=O)OC(C)(C)C)C(=O)O>>COC(=O)[C@H](C)N(Cc1ccc(F)cc1)C(=O)[C@@H](C)NC(=O)OC(C)(C)C
COC([C@H](C)NCC1=CC=C(C=C1)F)=O.C(C(C)C)OC(=O)Cl.C(C)(C)(C)OC(=O)N[C@@H](C(=O)O)C.CN1CCOCC1>>COC([C@H](C)N(CC1=CC=C(C=C1)F)C([C@@H](C)NC(=O)OC(C)(C)C)=O)=O
[CH3:1][O:2][C:3](=[O:4])[C@H:5]([CH3:6])[NH:7][CH2:8][c:9]1[cH:10][cH:11][c:12]([F:13])[cH:14][cH:15]1.O[C:16](=[O:17])[C@@H:18]([CH3:19])[NH:20][C:21](=[O:22])[O:23][C:24]([CH3:25])([CH3:26])[CH3:27]>>[CH3:1][O:2][C:3](=[O:4])[C@H:5]([CH3:6])[N:7]([CH2:8][c:9]1[cH:10][cH:11][c:12]([F:13])[cH:14][cH:15]1)[C:16](=[O:17...
COC(=O)[C@H](C)NCc1ccc(F)cc1.C[C@@H](NC(=O)OC(C)(C)C)C(=O)O
COC(=O)[C@H](C)N(Cc1ccc(F)cc1)C(=O)[C@@H](C)NC(=O)OC(C)(C)C
null
null
O1CCCC1
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
ac72df6259d5d7baee7abdbd4706ef4b4627f86ead9dc94f0cefcfcb37c21def
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C;D1;H3:4])-[#7:5]-[C:6](=[O;D1;H0:7])-[#8:8]-[C:9](-[C;D1;H3:10])(-[C;D1;H3:11])-[C;D1;H3:12].[C;D1;H3:13]-[#8:14]-[C:15](=[O;D1;H0:16])-[C:17](-[C;D1;H3:18])-[NH;D2;+0:19]-[C:20]-[c:21]>>[C;D1;H3:4]-[C:3](-[#7:5]-[C:6](=[O;D1;H0:7])-[#8:8]-[C:9](-[C;D1;H3:10])(-[C;D1;H3:11])-[C;...
69.7
[{"value": 69.7, "product": "COC([C@H](C)N(CC1=CC=C(C=C1)F)C([C@@H](C)NC(=O)OC(C)(C)C)=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
To a solution of (R)-2-tert-butoxycarbonylamino-propionic acid (37 g, 195 mmol) in dry tetrahydrofuran (250 mL) at 0° C. was added 4-methyl morpholine (21.5 mL, 195 mmol) followed by isobutylchloroformate (25.3 mL, 195 mmol). The reaction was allowed to warm to ambient temperature and stirred for two hours. This was fo...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
null
null
c1ccccc1
HO-
O1CCCC1
null
2
COC(=O)[C@H](C)NCc1ccc(F)cc1.C[C@@H](NC(=O)OC(C)(C)C)C(=O)O>O1CCCC1>COC(=O)[C@H](C)N(Cc1ccc(F)cc1)C(=O)[C@@H](C)NC(=O)OC(C)(C)C
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-c843a15b5d714641a5db49ffbd9018c2
COC(=O)[C@H](C)N(Cc1ccc(F)cc1)C(=O)[C@@H](C)NC(=O)OC(C)(C)C>>C[C@H]1NC(=O)[C@H](C)N(Cc2ccc(F)cc2)C1=O
COC([C@H](C)N(CC1=CC=C(C=C1)F)C([C@@H](C)NC(=O)OC(C)(C)C)=O)=O.FC(C(=O)O)(F)F>>FC1=CC=C(CN2C([C@H](NC([C@@H]2C)=O)C)=O)C=C1
COC(=O)[C@H:6]([CH3:7])[N:8]([CH2:9][c:10]1[cH:11][cH:12][c:13]([F:14])[cH:15][cH:16]1)[C:17]([C@@H:2]([CH3:1])[NH:3][C:4](OC(C)(C)C)=[O:5])=[O:18]>>[CH3:1][C@H:2]1[NH:3][C:4](=[O:5])[C@H:6]([CH3:7])[N:8]([CH2:9][c:10]2[cH:11][cH:12][c:13]([F:14])[cH:15][cH:16]2)[C:17]1=[O:18]
COC(=O)[C@H](C)N(Cc1ccc(F)cc1)C(=O)[C@@H](C)NC(=O)OC(C)(C)C
C[C@H]1NC(=O)[C@H](C)N(Cc2ccc(F)cc2)C1=O
null
null
ClCCl
C-C Coupling
OtherReaction
39ffc0aec208184cbe5c4ca2a02565c0e43f84f147cd00817fd9f8a86be7f3ec
068cd5629b3d99840ebb2991cb3eaa14690fdac6ebf4c6b53047fbd6cceb4255
O=C1CN(Cc2ccccc2)C(=O)CN1
C-O-C(=O)-[C@H;D3;+0:1](-[C;D1;H3:2])-[#7:3](-[C:4])-[C:5](=[O;D1;H0:6])-[C:7]-[#7:8]-[C;H0;D3;+0:9](=[O;D1;H0:10])-O-C(-C)(-C)-C>>[C:4]-[#7:3]1-[C:5](=[O;D1;H0:6])-[C:7]-[#7:8]-[C;H0;D3;+0:9](=[O;D1;H0:10])-[C@@H;D3;+0:1]-1-[C;D1;H3:2]
23
[{"value": 23.0, "product": "FC1=CC=C(CN2C([C@H](NC([C@@H]2C)=O)C)=O)C=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
To a solution of (2S)-2-[(2R)-(2-tert-butoxycarbonylamino-propionyl)-(4-fluoro-benzyl)-amino]-propionic acid methyl ester (43 g, 382 mmol) in dichloromethane (120 mL) at 0° C. was added trifluoroacetic acid (60 mL). The reaction was allowed to warm to ambient temperature and stirred for 2 hours. The reaction was cooled...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ester.Ether.Boc
Secondary amide
null
C1C[NH]CCN1
C1C[NH]CCN1.c1ccccc1
HO-
ClCCl
null
2
COC(=O)[C@H](C)N(Cc1ccc(F)cc1)C(=O)[C@@H](C)NC(=O)OC(C)(C)C>ClCCl>C[C@H]1NC(=O)[C@H](C)N(Cc2ccc(F)cc2)C1=O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-2b9d9636867a430cb92018a7cec32039
C[C@H]1NC(=O)[C@H](C)N(Cc2ccc(F)cc2)C1=O>>C[C@@H]1CN[C@@H](C)CN1Cc1ccc(F)cc1
FC1=CC=C(CN2C([C@H](NC([C@@H]2C)=O)C)=O)C=C1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>>FC1=CC=C(CN2[C@@H](CN[C@H](C2)C)C)C=C1
O=[C:3]1[C@H:2]([CH3:1])[N:8]([CH2:9][c:10]2[cH:11][cH:12][c:13]([F:14])[cH:15][cH:16]2)[C:7](=O)[C@@H:5]([CH3:6])[NH:4]1>>[CH3:1][C@@H:2]1[CH2:3][NH:4][C@@H:5]([CH3:6])[CH2:7][N:8]1[CH2:9][c:10]1[cH:11][cH:12][c:13]([F:14])[cH:15][cH:16]1
C[C@H]1NC(=O)[C@H](C)N(Cc2ccc(F)cc2)C1=O
C[C@@H]1CN[C@@H](C)CN1Cc1ccc(F)cc1
null
null
O1CCCC1
Reduction
OtherReaction
2222693cbc80ef6a16c214c8222fe58dea489881251dfa212831bf000001d833
1e111e1677c741c445104f499dde4d06874c64781551b41f18ee18795c631ec3
c1ccc(CN2CCNCC2)cc1
O=[C;H0;D3;+0:1]1-[#7:2]-[C:3](-[C;D1;H3:4])-[C;H0;D3;+0:5](=O)-[#7:6](-[C:7])-[C:8]-1-[C;D1;H3:9]>>[C:7]-[#7:6]1-[CH2;D2;+0:5]-[C:3](-[C;D1;H3:4])-[#7:2]-[CH2;D2;+0:1]-[C:8]-1-[C;D1;H3:9]
90.6
[{"value": 90.6, "product": "FC1=CC=C(CN2[C@@H](CN[C@H](C2)C)C)C=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of (3R,6S)-1-(4-fluoro-benzyl)-3,6-dimethyl-piperazine-2,5-dione (22 g, 87.9 mmol) in dry tetrahydrofuran (160 mL) at 0° C. was added a solution of lithium aluminum hydride (1M in tetrahydrofuran, 373 mL, 373 mmol) dropwise over 40 minutes. The reaction mixture was then refluxed for 4 hours, cooled to amb...
10.6084/m9.figshare.5104873.v1
null
Secondary amide.Tertiary amide
null
C1CNCC[NH]1
C1C[NH]CCN1
C1C[NH]CCN1.c1ccccc1
Other
O1CCCC1
null
null
C[C@H]1NC(=O)[C@H](C)N(Cc2ccc(F)cc2)C1=O>O1CCCC1>C[C@@H]1CN[C@@H](C)CN1Cc1ccc(F)cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-60ca7772c831497391bbb6d09424b31d
C[C@@H]1CN[C@@H](C)CN1Cc1ccc(F)cc1.Cc1ccc2c(c1)OC(=O)CC2>>Cc1ccc(CCC(=O)N2C[C@H](C)N(Cc3ccc(F)cc3)C[C@H]2C)c(O)c1
FC1=CC=C(CN2[C@@H](CN[C@H](C2)C)C)C=C1.CC1=CC=C2CCC(OC2=C1)=O>>FC1=CC=C(CN2C[C@H](N(C[C@@H]2C)C(CCC2=C(C=C(C=C2)C)O)=O)C)C=C1
[NH:10]1[CH2:11][C@@H:12]([CH3:13])[N:14]([CH2:15][c:16]2[cH:17][cH:18][c:19]([F:20])[cH:21][cH:22]2)[CH2:23][C@@H:24]1[CH3:25].[CH3:1][c:2]1[cH:3][cH:4][c:5]2[c:26]([cH:28]1)[O:27][C:8](=[O:9])[CH2:7][CH2:6]2>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([CH2:6][CH2:7][C:8](=[O:9])[N:10]2[CH2:11][C@H:12]([CH3:13])[N:14]([CH2:15][c:...
C[C@@H]1CN[C@@H](C)CN1Cc1ccc(F)cc1.Cc1ccc2c(c1)OC(=O)CC2
Cc1ccc(CCC(=O)N2C[C@H](C)N(Cc3ccc(F)cc3)C[C@H]2C)c(O)c1
null
null
C1(=CC=CC=C1)C
Acylation
OtherReaction
dc21ff2b157e54c9886fd241d9fd249bb6a60abdcf01f136b737377190871de0
f44eeb513838e5dc505e102b5199fe85d83755bec10694d688dc5fa8c8eea5db
O=C(CCc1ccccc1)N1CCN(Cc2ccccc2)CC1
[C;D1;H3:1]-[C:2]1-[C:3]-[#7:4]-[C:5]-[C:6]-[NH;D2;+0:7]-1.[O;D1;H0:8]=[C;H0;D3;+0:9]1-[C:10]-[C:11]-[c:12]:[c:13](:[c:14])-[O;H0;D2;+0:15]-1>>[C;D1;H3:1]-[C:2]1-[C:3]-[#7:4]-[C:5]-[C:6]-[N;H0;D3;+0:7]-1-[C;H0;D3;+0:9](=[O;D1;H0:8])-[C:10]-[C:11]-[c:12]:[c:13](-[OH;D1;+0:15]):[c:14]
79
[{"value": 79.0, "product": "FC1=CC=C(CN2C[C@H](N(C[C@@H]2C)C(CCC2=C(C=C(C=C2)C)O)=O)C)C=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of (2R,5S)-1-(4-fluoro-benzyl)-2,5-dimethyl-piperazine (0.25 g, 1.12 mmol) in toluene (10 mL) was added 7-methyl-chroman-2-one (0.25 g, 1.54 mmol) and the resulting solution was heated to reflux for 48 hours. The reaction was cooled, concentrated in vacuo and purified via chromatography on silica gel to g...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary amine
Tertiary amide.Aromatic alcohol
C1CNCC[NH]1.c1ccc2c(c1)CCCO2
C1C[NH]CC[NH]1
c1ccccc1.C1C[NH]CC[NH]1.c1ccccc1
null
C1(=CC=CC=C1)C
null
null
C[C@@H]1CN[C@@H](C)CN1Cc1ccc(F)cc1.Cc1ccc2c(c1)OC(=O)CC2>C1(=CC=CC=C1)C>Cc1ccc(CCC(=O)N2C[C@H](C)N(Cc3ccc(F)cc3)C[C@H]2C)c(O)c1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-7f8f1f63cfdc4540b5a25b5d637eae2a
COC(=O)CBr.Cc1ccc(CCC(=O)N2C[C@H](C)N(Cc3ccc(F)cc3)C[C@H]2C)c(O)c1>>COC(=O)COc1cc(C)ccc1CCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
COC(CBr)=O.FC1=CC=C(CN2C[C@H](N(C[C@@H]2C)C(CCC2=C(C=C(C=C2)C)O)=O)C)C=C1.[H-].[Na+]>>COC(COC1=C(C=CC(=C1)C)CCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C)=O
Br[CH2:5][C:3]([O:2][CH3:1])=[O:4].[OH:6][c:7]1[cH:8][c:9]([CH3:10])[cH:11][cH:12][c:13]1[CH2:14][CH2:15][C:16](=[O:17])[N:18]1[CH2:19][C@H:20]([CH3:21])[N:22]([CH2:23][c:24]2[cH:25][cH:26][c:27]([F:28])[cH:29][cH:30]2)[CH2:31][C@H:32]1[CH3:33]>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][O:6][c:7]1[cH:8][c:9]([CH3:10])[cH:11][cH...
COC(=O)CBr.Cc1ccc(CCC(=O)N2C[C@H](C)N(Cc3ccc(F)cc3)C[C@H]2C)c(O)c1
COC(=O)COc1cc(C)ccc1CCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
null
null
O1CCCC1
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
50d675b335c583a6ce22e1164b27a78b18b9ca447d45137820c344bcb6369217
0865de4e1853c59ac25437e36fd18b03329566cb9eff4b4f0ce70d5714692fd3
O=C(CCc1ccccc1)N1CCN(Cc2ccccc2)CC1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5].[OH;D1;+0:6]-[c:7](:[c:8]):[c:9]>>[C;D1;H3:5]-[#8:4]-[C:2](=[O;D1;H0:3])-[CH2;D2;+0:1]-[O;H0;D2;+0:6]-[c:7](:[c:8]):[c:9]
103.8
[{"value": 103.8, "product": "COC(COC1=C(C=CC(=C1)C)CCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
5
MINUTE
To a solution of 1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-3-(2-hydroxy-4-methyl-phenyl)-propan-1-one, (0.15 g, 0.38 mmol) in tetrahydrofuran (2 mL) at 0° C. was added sodium hydride (0.023 g, 0.57 mmol). The reaction was stirred for 5 minutes, then bromoacetic acid methyl ester (0.043 mL, 0.45 mmol) ...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Aromatic alcohol
Ester.Ether
null
null
c1ccccc1.C1C[NH]CC[NH]1.c1ccccc1
HBr
O1CCCC1
null
0.083333
COC(=O)CBr.Cc1ccc(CCC(=O)N2C[C@H](C)N(Cc3ccc(F)cc3)C[C@H]2C)c(O)c1>O1CCCC1>COC(=O)COc1cc(C)ccc1CCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-87154cd5bc314ab29bbd3e6f8b4b4c8f
COC(=O)COc1cc(C)ccc1CCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C>>Cc1ccc(CCC(=O)N2C[C@H](C)N(Cc3ccc(F)cc3)C[C@H]2C)c(OCC(=O)O)c1
COC(COC1=C(C=CC(=C1)C)CCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C)=O.O1CCCC1.CO.O.[OH-].[Li+]>>FC1=CC=C(CN2C[C@H](N(C[C@@H]2C)C(CCC2=C(OCC(=O)O)C=C(C=C2)C)=O)C)C=C1
C[O:31][C:29]([CH2:28][O:27][c:26]1[c:5]([CH2:6][CH2:7][C:8](=[O:9])[N:10]2[CH2:11][C@H:12]([CH3:13])[N:14]([CH2:15][c:16]3[cH:17][cH:18][c:19]([F:20])[cH:21][cH:22]3)[CH2:23][C@H:24]2[CH3:25])[cH:4][cH:3][c:2]([CH3:1])[cH:32]1)=[O:30]>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([CH2:6][CH2:7][C:8](=[O:9])[N:10]2[CH2:11][C@H:12]([...
COC(=O)COc1cc(C)ccc1CCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
Cc1ccc(CCC(=O)N2C[C@H](C)N(Cc3ccc(F)cc3)C[C@H]2C)c(OCC(=O)O)c1
null
null
O.Cl
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(CCc1ccccc1)N1CCN(Cc2ccccc2)CC1
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]
90.4
[{"value": 90.4, "product": "FC1=CC=C(CN2C[C@H](N(C[C@@H]2C)C(CCC2=C(OCC(=O)O)C=C(C=C2)C)=O)C)C=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
To a solution of (2-{3-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-3-oxo-propyl}-5-methyl-phenoxy)-acetic acid methyl ester (0.18 g, 0.40 mmol) in 2:2:1 tetrahydrofuran:methanol:water (5 mL) was added lithium hydroxide hydrate (0.026 g, 0.62 mmol) and the reaction was stirred at ambient temperature for 2 ...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.C1C[NH]CC[NH]1.c1ccccc1
Other
O.Cl
null
2
COC(=O)COc1cc(C)ccc1CCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C>O.Cl>Cc1ccc(CCC(=O)N2C[C@H](C)N(Cc3ccc(F)cc3)C[C@H]2C)c(OCC(=O)O)c1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-7c1427aeb6c74cd89a227305147d78b4
CS(N)(=O)=O.Cc1ccc(CCC(=O)N2C[C@H](C)N(Cc3ccc(F)cc3)C[C@H]2C)c(OCC(=O)O)c1>>Cc1ccc(CCC(=O)N2C[C@H](C)N(Cc3ccc(F)cc3)C[C@H]2C)c(OCC(=O)NS(C)(=O)=O)c1
FC1=CC=C(CN2C[C@H](N(C[C@@H]2C)C(CCC2=C(OCC(=O)O)C=C(C=C2)C)=O)C)C=C1.Cl.CN(CCCN=C=NCC)C.CS(=O)(=O)N.C(C)N(CC)CC>>FC1=CC=C(CN2C[C@H](N(C[C@@H]2C)C(CCC2=C(OCC(=O)NS(=O)(=O)C)C=C(C=C2)C)=O)C)C=C1
[NH2:31][S:32]([CH3:33])(=[O:34])=[O:35].O[C:29]([CH2:28][O:27][c:26]1[c:5]([CH2:6][CH2:7][C:8](=[O:9])[N:10]2[CH2:11][C@H:12]([CH3:13])[N:14]([CH2:15][c:16]3[cH:17][cH:18][c:19]([F:20])[cH:21][cH:22]3)[CH2:23][C@H:24]2[CH3:25])[cH:4][cH:3][c:2]([CH3:1])[cH:36]1)=[O:30]>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([CH2:6][CH2:7][C:...
CS(N)(=O)=O.Cc1ccc(CCC(=O)N2C[C@H](C)N(Cc3ccc(F)cc3)C[C@H]2C)c(OCC(=O)O)c1
Cc1ccc(CCC(=O)N2C[C@H](C)N(Cc3ccc(F)cc3)C[C@H]2C)c(OCC(=O)NS(C)(=O)=O)c1
null
CN(C1=CC=NC=C1)C
ClCCl.C(Cl)Cl
Acylation
Carboxylic acid with primary amine to amide
195a412a8235704efe2985cdc18467ba661e632bab7b61944399ecc813e32a09
5e4665bad9c6f58dddd98c5f95e436c640b4c0118b04efea5cd58c7d1755401d
O=C(CCc1ccccc1)N1CCN(Cc2ccccc2)CC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[#8:4].[C;D1;H3:5]-[#16:6](-[NH2;D1;+0:7])(=[O;D1;H0:8])=[O;D1;H0:9]>>[#8:4]-[C:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:7]-[#16:6](-[C;D1;H3:5])(=[O;D1;H0:8])=[O;D1;H0:9]
80.2
[{"value": 80.2, "product": "FC1=CC=C(CN2C[C@H](N(C[C@@H]2C)C(CCC2=C(OCC(=O)NS(=O)(=O)C)C=C(C=C2)C)=O)C)C=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
18
HOUR
To a solution of (2-{3-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-3-oxo-propyl}-5-methyl-phenoxy)-acetic acid (0.052 g, 0.12 mmol) in methylene chloride (1 mL) was added 4-dimethylaminopyridine (0.022 g, 0.18 mmol), (3-(dimethylamino)propyl)ethyl carbodiimide hydrochloride (0.032 g, 0.17 mmol), methanesu...
10.6084/m9.figshare.5104873.v1
null
Sulfonamide.Carboxylic acid
Sulfonamide.Secondary amide
null
null
c1ccccc1.C1C[NH]CC[NH]1.c1ccccc1
HO-
CN(C1=CC=NC=C1)C.ClCCl.C(Cl)Cl
null
18
CS(N)(=O)=O.Cc1ccc(CCC(=O)N2C[C@H](C)N(Cc3ccc(F)cc3)C[C@H]2C)c(OCC(=O)O)c1>CN(C1=CC=NC=C1)C.ClCCl.C(Cl)Cl>Cc1ccc(CCC(=O)N2C[C@H](C)N(Cc3ccc(F)cc3)C[C@H]2C)c(OCC(=O)NS(C)(=O)=O)c1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-b437499df33d48f784286683f8fd74db
COc1cc(Cl)ccc1O.O=C(O)CCl>>COc1cc(Cl)ccc1OCC(=O)O
Cl.[OH-].[Na+].ClC1=CC(=C(C=C1)O)OC.ClCC(=O)O>>ClC1=CC(=C(OCC(=O)O)C=C1)OC
[CH3:1][O:2][c:3]1[cH:4][c:5]([Cl:6])[cH:7][cH:8][c:9]1[OH:10].Cl[CH2:11][C:12](=[O:13])[OH:14]>>[CH3:1][O:2][c:3]1[cH:4][c:5]([Cl:6])[cH:7][cH:8][c:9]1[O:10][CH2:11][C:12](=[O:13])[OH:14]
COc1cc(Cl)ccc1O.O=C(O)CCl
COc1cc(Cl)ccc1OCC(=O)O
null
null
O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
c1ccccc1
Cl-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[O;D1;H1:4].[OH;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[O;D1;H0:3]=[C:2](-[O;D1;H1:4])-[CH2;D2;+0:1]-[O;H0;D2;+0:5]-[c:6](:[c:7]):[c:8]
120
[{"value": 120.0, "product": "ClC1=CC(=C(OCC(=O)O)C=C1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
95
CELSIUS
3
HOUR
To a solution of sodium hydroxide (6.6 g, 160 mmol) in water (45 mL) was added 4-chloro-2-methoxy-phenol (2.0 mL, 16 mmol) and chloroacetic acid (7.7 g, 81 mmol). The resulting mixture was heated to 95° C. and stirred for three hours. The reaction was allowed to cool to ambient temperature and slowly acidified with con...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1
HCl
O
95
3
COc1cc(Cl)ccc1O.O=C(O)CCl>O>COc1cc(Cl)ccc1OCC(=O)O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-a62f0d2dcbcb40f2a0c77212a8c65747
COc1cc(Cl)ccc1OCC(=O)O>>O=C(O)COc1ccc(Cl)cc1O
[Br-].ClC1=CC(=C(OCC(=O)O)C=C1)OC>>ClC1=CC(=C(OCC(=O)O)C=C1)O
C[O:13][c:12]1[c:6]([O:5][CH2:4][C:2](=[O:1])[OH:3])[cH:7][cH:8][c:9]([Cl:10])[cH:11]1>>[O:1]=[C:2]([OH:3])[CH2:4][O:5][c:6]1[cH:7][cH:8][c:9]([Cl:10])[cH:11][c:12]1[OH:13]
COc1cc(Cl)ccc1OCC(=O)O
O=C(O)COc1ccc(Cl)cc1O
null
null
O
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccccc1
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
To a solution of 48% aqueous hyrdrogen bromide (20 mL) was added (4-chloro-2-methoxy-phenoxy)-acetic acid (2.1 g, 9.7 mmol). The resulting mixture was heated to reflux overnight. The mixture was cooled to ambient temperature, diluted with water and extracted with diethyl ether. The organic layer was dried over magnesiu...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccccc1
Other
O
null
null
COc1cc(Cl)ccc1OCC(=O)O>O>O=C(O)COc1ccc(Cl)cc1O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-3fa15cbc844647a681a1b88e23376cc0
C[C@@H]1CN[C@@H](C)CN1Cc1ccc(F)cc1.O=C1COc2ccc(Cl)cc2O1>>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1O
ClC=1C=CC2=C(OC(CO2)=O)C1.FC1=CC=C(CN2[C@@H](CN[C@H](C2)C)C)C=C1>>ClC1=CC(=C(OCC(=O)N2[C@@H](CN([C@H](C2)C)CC2=CC=C(C=C2)F)C)C=C1)O
[CH3:1][C@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)[C@H:13]([CH3:14])[CH2:15][NH:16]1.[C:17]1(=[O:18])[CH2:19][O:20][c:21]2[cH:22][cH:23][c:24]([Cl:25])[cH:26][c:27]2[O:28]1>>[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)[C@@H:13]([CH3:14])[CH2:15][N:1...
C[C@@H]1CN[C@@H](C)CN1Cc1ccc(F)cc1.O=C1COc2ccc(Cl)cc2O1
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1O
null
null
C1(=CC=CC=C1)C
Acylation
OtherReaction
6c0900bd46f51c9090197774b1f18e79f46c457766aa8aebe292b16c1b938f4f
f44eeb513838e5dc505e102b5199fe85d83755bec10694d688dc5fa8c8eea5db
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
[C;D1;H3:1]-[C:2]1-[C:3]-[#7:4]-[C:5]-[C:6]-[NH;D2;+0:7]-1.[O;D1;H0:8]=[C;H0;D3;+0:9]1-[C:10]-[#8:11]-[c:12]:[c:13](:[c:14])-[O;H0;D2;+0:15]-1>>[C;D1;H3:1]-[C:2]1-[C:3]-[#7:4]-[C:5]-[C:6]-[N;H0;D3;+0:7]-1-[C;H0;D3;+0:9](=[O;D1;H0:8])-[C:10]-[#8:11]-[c:12]:[c:13](-[OH;D1;+0:15]):[c:14]
63.3
[{"value": 63.3, "product": "ClC1=CC(=C(OCC(=O)N2[C@@H](CN([C@H](C2)C)CC2=CC=C(C=C2)F)C)C=C1)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
95
CELSIUS
null
null
To a solution of 7-chloro-benzo[1,4]dioxin-2-one (0.48 g, 2.6 mmol) in toluene (5 mL) was added 1-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazine (0.59 g, 2.6 mmol). The resulting mixture was heated to 95° C. overnight. The reaction was cooled to ambient temperature and concentrated in vacuo. Chromatography on silica...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary amine
Tertiary amide.Aromatic alcohol
C1CNCC[NH]1.c1ccc2c(c1)OCCO2
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1
null
C1(=CC=CC=C1)C
95
null
C[C@@H]1CN[C@@H](C)CN1Cc1ccc(F)cc1.O=C1COc2ccc(Cl)cc2O1>C1(=CC=CC=C1)C>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-828f525a56584702a50c7b8b62725b8b
COC(=O)CBr.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1O>>COC(=O)COc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
ClC1=CC(=C(OCC(=O)N2[C@@H](CN([C@H](C2)C)CC2=CC=C(C=C2)F)C)C=C1)O.COC(CBr)=O.C([O-])([O-])=O.[Cs+].[Cs+]>>COC(COC1=C(C=CC(=C1)Cl)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C)=O
Br[CH2:5][C:3]([O:2][CH3:1])=[O:4].[OH:6][c:7]1[cH:8][c:9]([Cl:10])[cH:11][cH:12][c:13]1[O:14][CH2:15][C:16](=[O:17])[N:18]1[CH2:19][C@H:20]([CH3:21])[N:22]([CH2:23][c:24]2[cH:25][cH:26][c:27]([F:28])[cH:29][cH:30]2)[CH2:31][C@H:32]1[CH3:33]>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][O:6][c:7]1[cH:8][c:9]([Cl:10])[cH:11][cH:12]...
COC(=O)CBr.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1O
COC(=O)COc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
null
null
O1CCOCC1
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
50d675b335c583a6ce22e1164b27a78b18b9ca447d45137820c344bcb6369217
0865de4e1853c59ac25437e36fd18b03329566cb9eff4b4f0ce70d5714692fd3
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5].[OH;D1;+0:6]-[c:7](:[c:8]):[c:9]>>[C;D1;H3:5]-[#8:4]-[C:2](=[O;D1;H0:3])-[CH2;D2;+0:1]-[O;H0;D2;+0:6]-[c:7](:[c:8]):[c:9]
169.8
[{"value": 169.8, "product": "COC(COC1=C(C=CC(=C1)Cl)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
To a solution of 2-(4-chloro-2-hydroxy-phenoxy)-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone (0.30 g, 0.75 mmol) and bromo-acetic acid methyl ester (0.14 mL, 1.5 mmol) in dioxane (3 mL) was added cesium carbonate (0.50 g, 1.5 mmol). The resulting mixture was stirred at ambient temperature overni...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Aromatic alcohol
Ester.Ether
null
null
c1ccccc1.C1C[NH]CC[NH]1.c1ccccc1
HBr
O1CCOCC1
null
8
COC(=O)CBr.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1O>O1CCOCC1>COC(=O)COc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-0ad60219dd484f4eafc9f52d082067ec
COC(=O)COc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C>>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1OCC(=O)O
Cl.COC(COC1=C(C=CC(=C1)Cl)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C)=O.O.[OH-].[Li+]>>ClC=1C=CC(=C(OCC(=O)O)C1)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C
C[O:32][C:30]([CH2:29][O:28][c:27]1[c:21]([O:20][CH2:19][C:17]([N:16]2[C@H:2]([CH3:1])[CH2:3][N:4]([CH2:5][c:6]3[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]3)[C@@H:13]([CH3:14])[CH2:15]2)=[O:18])[cH:22][cH:23][c:24]([Cl:25])[cH:26]1)=[O:31]>>[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)...
COC(=O)COc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1OCC(=O)O
null
null
CO.O.O1CCCC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
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]
74.8
[{"value": 74.8, "product": "ClC=1C=CC(=C(OCC(=O)O)C1)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
To a solution of (5-chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-phenoxy)-acetic acid methyl ester (0.21 g, 0.46 mmol) in methanol (2 mL), tetrahydrofuran (2 mL) and water (1 mL) was added lithium hydroxide monohydrate (0.039 g, 0.93 mmol). The resulting mixture was stirred at amb...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1
Other
CO.O.O1CCCC1
null
3
COC(=O)COc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C>CO.O.O1CCCC1>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1OCC(=O)O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-f44ef485b6494d718fea161cc4781aaa
CS(N)(=O)=O.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1OCC(=O)O>>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1OCC(=O)NS(C)(=O)=O
ClC=1C=CC(=C(OCC(=O)O)C1)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C.Cl.CN(CCCN=C=NCC)C.CS(=O)(=O)N.C(C)N(CC)CC>>ClC=1C=CC(=C(OCC(=O)NS(=O)(=O)C)C1)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C
[NH2:32][S:33]([CH3:34])(=[O:35])=[O:36].O[C:30]([CH2:29][O:28][c:27]1[c:21]([O:20][CH2:19][C:17]([N:16]2[C@H:2]([CH3:1])[CH2:3][N:4]([CH2:5][c:6]3[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]3)[C@@H:13]([CH3:14])[CH2:15]2)=[O:18])[cH:22][cH:23][c:24]([Cl:25])[cH:26]1)=[O:31]>>[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7]...
CS(N)(=O)=O.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1OCC(=O)O
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1OCC(=O)NS(C)(=O)=O
null
CN(C1=CC=NC=C1)C
ClCCl.C(Cl)Cl
Acylation
Carboxylic acid with primary amine to amide
195a412a8235704efe2985cdc18467ba661e632bab7b61944399ecc813e32a09
5e4665bad9c6f58dddd98c5f95e436c640b4c0118b04efea5cd58c7d1755401d
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[#8:4].[C;D1;H3:5]-[#16:6](-[NH2;D1;+0:7])(=[O;D1;H0:8])=[O;D1;H0:9]>>[#8:4]-[C:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:7]-[#16:6](-[C;D1;H3:5])(=[O;D1;H0:8])=[O;D1;H0:9]
null
[]
null
null
3
DAY
To a solution of (5-chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-phenoxy)-acetic acid (0.051 g, 0.10 mmol) in methylene chloride (1 mL) was added 4-dimethylaminopyridine (0.022 g, 0.18 mmol), (3-(dimethylamino)propyl)ethyl carbodiimide hydrochloride (0.033 g, 0.17 mmol), methanesu...
10.6084/m9.figshare.5104873.v1
null
Sulfonamide.Carboxylic acid
Sulfonamide.Secondary amide
null
null
C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1
HO-
CN(C1=CC=NC=C1)C.ClCCl.C(Cl)Cl
null
72
CS(N)(=O)=O.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1OCC(=O)O>CN(C1=CC=NC=C1)C.ClCCl.C(Cl)Cl>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1OCC(=O)NS(C)(=O)=O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-9b2b8380db7e41eda5472024bba50d5f
CCOC(=O)[C@H](C)O.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1O>>CCOC(=O)C(C)Oc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
ClC1=CC(=C(OCC(=O)N2[C@@H](CN([C@H](C2)C)CC2=CC=C(C=C2)F)C)C=C1)O.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C(C)OC([C@H](C)O)=O.C(C)OC(=O)N=NC(=O)OCC>>C(C)OC(C(C)OC1=C(C=CC(=C1)Cl)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C)=O
O[C@H:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[CH3:7].[OH:8][c:9]1[cH:10][c:11]([Cl:12])[cH:13][cH:14][c:15]1[O:16][CH2:17][C:18](=[O:19])[N:20]1[CH2:21][C@H:22]([CH3:23])[N:24]([CH2:25][c:26]2[cH:27][cH:28][c:29]([F:30])[cH:31][cH:32]2)[CH2:33][C@H:34]1[CH3:35]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]([CH3:7])[O:8][c:9]1[c...
CCOC(=O)[C@H](C)O.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1O
CCOC(=O)C(C)Oc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
null
null
O1CCCC1
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
dcfcc873dea6ee5e165c0ecd29b721f7fe5378b92b644a66f7b493dd677cb7f9
23ac5fc1d8cc7460c5f165241138db5f1d60f846b59bf6c4b239ddd29d58ddda
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
O-[C@@H;D3;+0:1](-[C;D1;H3:2])-[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])-[CH;D3;+0:1](-[C;D1;H3:2])-[O;H0;D2;+0:7]-[c:8](:[c:9]):[c:10]
85.5
[{"value": 85.5, "product": "C(C)OC(C(C)OC1=C(C=CC(=C1)Cl)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
To a solution of 2-(4-chloro-2-hydroxy-phenoxy)-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone (0.076 g, 0.18 mmol), triphenylphosphine (0.076 g, 0.29 mmol) and (2S)-2-hydroxy-propionic acid ethyl ester (0.036 g, 0.31 mmol) in tetrahydrofuran (1 mL) was added diethyl-azodicarboxylate (0.049 g, 0.2...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary alcohol.Aromatic alcohol
Ester.Ether
null
null
c1ccccc1.C1C[NH]CC[NH]1.c1ccccc1
HO-
O1CCCC1
null
8
CCOC(=O)[C@H](C)O.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1O>O1CCCC1>CCOC(=O)C(C)Oc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-1df5b5df44fb43f082eaff3a52802315
CCOC(=O)C(C)Oc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C>>CC(Oc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C)C(=O)O
Cl.C(C)OC(C(C)OC1=C(C=CC(=C1)Cl)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C)=O.O.[OH-].[Li+]>>ClC=1C=CC(=C(OC(C(=O)O)C)C1)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C
CC[O:33][C:31]([CH:2]([CH3:1])[O:3][c:4]1[cH:5][c:6]([Cl:7])[cH:8][cH:9][c:10]1[O:11][CH2:12][C:13](=[O:14])[N:15]1[CH2:16][C@H:17]([CH3:18])[N:19]([CH2:20][c:21]2[cH:22][cH:23][c:24]([F:25])[cH:26][cH:27]2)[CH2:28][C@H:29]1[CH3:30])=[O:32]>>[CH3:1][CH:2]([O:3][c:4]1[cH:5][c:6]([Cl:7])[cH:8][cH:9][c:10]1[O:11][CH2:12][...
CCOC(=O)C(C)Oc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
CC(Oc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C)C(=O)O
null
null
CO.O.O1CCCC1
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
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]
91.9
[{"value": 91.9, "product": "ClC=1C=CC(=C(OC(C(=O)O)C)C1)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
To a solution of 2-(5-chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-phenoxy)-propionic acid ethyl ester (0.075 g, 0.15 mmol) in methanol (0.4 mL), tetrahydrofuran (0.4 mL) and water (0.2 mL) was added lithium hydroxide monohydrate (0.010 g, 0.24 mmol). The resulting mixture was sti...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.C1C[NH]CC[NH]1.c1ccccc1
Other
CO.O.O1CCCC1
null
3
CCOC(=O)C(C)Oc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C>CO.O.O1CCCC1>CC(Oc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C)C(=O)O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-44dafea2b06842acb7dacd01a2391aa6
CCO.O=C(O)CCC(=O)c1cc(Cl)ccc1O>>CCOC(=O)CCC(=O)c1cc(Cl)ccc1O
ClC=1C=CC(=C(C1)C(CCC(=O)O)=O)O.Cl.C(C)O>>C(C)OC(CCC(=O)C1=C(C=CC(=C1)Cl)O)=O
[CH3:1][CH2:2][OH:3].O[C:4](=[O:5])[CH2:6][CH2:7][C:8](=[O:9])[c:10]1[cH:11][c:12]([Cl:13])[cH:14][cH:15][c:16]1[OH:17]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][CH2:7][C:8](=[O:9])[c:10]1[cH:11][c:12]([Cl:13])[cH:14][cH:15][c:16]1[OH:17]
CCO.O=C(O)CCC(=O)c1cc(Cl)ccc1O
CCOC(=O)CCC(=O)c1cc(Cl)ccc1O
null
null
null
Protection
Esterification of Carboxylic Acids
070670f68a20c1021da94fabee54def4688122fb721af5f52cd5a03630845d0e
0d8a72b7375d91aa7263e766e03a3cb7c4fa91e27abcd590409ff03b98eed690
c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[C:4]-[C:5]=[O;D1;H0:6].[C;D1;H3:7]-[C:8]-[OH;D1;+0:9]>>[C;D1;H3:7]-[C:8]-[O;H0;D2;+0:9]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[C:4]-[C:5]=[O;D1;H0:6]
null
[]
null
null
null
null
A solution of 4-(5-chloro-2-hydroxy-phenyl)-4-oxo-butyric acid (0.25 g, 1.09 mmol) in ethanol (10 mL) saturated with hydrogen chloride (g) was stirred at ambient temperature for 12 hours. The reaction was concentrated in vacuo, dissolved in diethyl ether and washed with saturated aqueous sodium bicarbonate. The organic...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary alcohol
Ester
null
null
c1ccccc1
HO-
null
null
null
CCO.O=C(O)CCC(=O)c1cc(Cl)ccc1O>>CCOC(=O)CCC(=O)c1cc(Cl)ccc1O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-fe8e31829e854627b42103dff1a859eb
CCOC(=O)CCC(=O)c1cc(Cl)ccc1O.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)CCl>>CCOC(=O)CCC(=O)c1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
ClCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C.C(C)OC(CCC(=O)C1=C(C=CC(=C1)Cl)O)=O.C1CNC2=NCCCN2C1>>C(C)OC(CCC(=O)C1=C(C=CC(=C1)Cl)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C)=O
[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][CH2:7][C:8](=[O:9])[c:10]1[cH:11][c:12]([Cl:13])[cH:14][cH:15][c:16]1[OH:17].Cl[CH2:18][C:19](=[O:20])[N:21]1[CH2:22][C@H:23]([CH3:24])[N:25]([CH2:26][c:27]2[cH:28][cH:29][c:30]([F:31])[cH:32][cH:33]2)[CH2:34][C@H:35]1[CH3:36]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][CH2:7][C:8](...
CCOC(=O)CCC(=O)c1cc(Cl)ccc1O.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)CCl
CCOC(=O)CCC(=O)c1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
null
null
C(C)#N
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
Cl-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#7:4](-[C:5])-[C:6].[O;D1;H0:7]=[C:8]-[c:9]:[c:10](-[OH;D1;+0:11]):[c:12]>>[C:5]-[#7:4](-[C:2](=[O;D1;H0:3])-[CH2;D2;+0:1]-[O;H0;D2;+0:11]-[c:10](:[c:12]):[c:9]-[C:8]=[O;D1;H0:7])-[C:6]
45
[{"value": 45.0, "product": "C(C)OC(CCC(=O)C1=C(C=CC(=C1)Cl)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
12
HOUR
A solution of 2-chloro-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone (0.11 g, 0.36 mmol), 4-(5-chloro-2-hydroxy-phenyl)-4-oxo-butyric acid ethyl ester (0.11 g, 0.43 mmol) and 1,5,7-triazabicyclo[4,4,0]dec-5-ene bound to polystyrene crosslinked with 2% DVB (0.21 g, 0.54 mmol) in acetonitrile (1.8 ...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.C1C[NH]CC[NH]1.c1ccccc1
HCl
C(C)#N
null
12
CCOC(=O)CCC(=O)c1cc(Cl)ccc1O.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)CCl>C(C)#N>CCOC(=O)CCC(=O)c1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-a03833925d5e4fcc95b698c04ab760a1
CCOC(=O)CCC(=O)c1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C>>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1C(=O)CCC(=O)O
C(C)OC(CCC(=O)C1=C(C=CC(=C1)Cl)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C)=O.O1CCCC1.CO.O.[OH-].[Li+]>>ClC=1C=CC(=C(C1)C(CCC(=O)O)=O)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C
CC[O:34][C:32]([CH2:31][CH2:30][C:28]([c:27]1[c:21]([O:20][CH2:19][C:17]([N:16]2[C@H:2]([CH3:1])[CH2:3][N:4]([CH2:5][c:6]3[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]3)[C@@H:13]([CH3:14])[CH2:15]2)=[O:18])[cH:22][cH:23][c:24]([Cl:25])[cH:26]1)=[O:29])=[O:33]>>[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10...
CCOC(=O)CCC(=O)c1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1C(=O)CCC(=O)O
null
null
O
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
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]
91.7
[{"value": 91.7, "product": "ClC=1C=CC(=C(C1)C(CCC(=O)O)=O)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
12
HOUR
To a solution of 4-(5-chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-phenyl)-4-oxo-butyric acid ethyl ester (0.082 g, 0.16 mmol) in 2:2:1 tetrahydrofuran:methanol:water(1.5 mL) was added lithium hydroxide monohydrate (0.34 g, 0.79 mmol). The resulting solution was stirred 12 hours a...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1
Other
O
null
12
CCOC(=O)CCC(=O)c1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C>O>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1C(=O)CCC(=O)O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-47c853a443844d0ebba44d6152144a8d
C[C@@H]1CNCCN1.Fc1ccc(CCl)cc1>>C[C@@H]1CN(Cc2ccc(F)cc2)CCN1
C[C@H]1NCCNC1.FC1=CC=C(CCl)C=C1.C(O)([O-])=O.[Na+]>>FC1=CC=C(CN2C[C@H](NCC2)C)C=C1
[CH3:1][C@@H:2]1[CH2:3][NH:4][CH2:13][CH2:14][NH:15]1.Cl[CH2:5][c:6]1[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]1>>[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)[CH2:13][CH2:14][NH:15]1
C[C@@H]1CNCCN1.Fc1ccc(CCl)cc1
C[C@@H]1CN(Cc2ccc(F)cc2)CCN1
null
null
C(C)O
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
f302e0798768754bbc60184db743cc667f2eb421e32357dcb3b8d027a535a203
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
c1ccc(CN2CCNCC2)cc1
Cl-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[#7:5]1-[C:6]-[C:7]-[NH;D2;+0:8]-[C:9]-[C:10]-1>>[c:3]:[c:2](-[CH2;D2;+0:1]-[N;H0;D3;+0:8]1-[C:7]-[C:6]-[#7:5]-[C:10]-[C:9]-1):[c:4]
53.3
[{"value": 53.3, "product": "FC1=CC=C(CN2C[C@H](NCC2)C)C=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of (2R)-2-methyl-piperizine (4.5 g, 45 mmol) in ethanol (80 mL) was added 4-fluorobenzyl chloride (5.38 mL, 45.0 mmol) and sodium hydrogen carbonate (11.3 g, 135 mmol). The reaction was refluxed overnight, cooled and concentrated. The remaining residue was diluted with dichloromethane and washed with wate...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CNCCN1
C1CNCC[NH]1
C1CNCC[NH]1.c1ccccc1
HCl
C(C)O
null
null
C[C@@H]1CNCCN1.Fc1ccc(CCl)cc1>C(C)O>C[C@@H]1CN(Cc2ccc(F)cc2)CCN1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-03d958e6728f4420bdfbc1d54303f87c
C[C@@H]1CN(Cc2ccc(F)cc2)CCN1.O=C(Cl)CCl>>C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)CCl
ClCC(=O)Cl.FC1=CC=C(CN2C[C@H](NCC2)C)C=C1.C(C)N(CC)CC>>ClCC(=O)N1[C@@H](CN(CC1)CC1=CC=C(C=C1)F)C
[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)[CH2:13][CH2:14][NH:15]1.Cl[C:16](=[O:17])[CH2:18][Cl:19]>>[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)[CH2:13][CH2:14][N:15]1[C:16](=[O:17])[CH2:18][Cl:19]
C[C@@H]1CN(Cc2ccc(F)cc2)CCN1.O=C(Cl)CCl
C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)CCl
null
null
ClCCl
Acylation
N-alkylation of secondary amines with alkyl halides
6dd420fad17fb719b6bd840e8952a8d7b2fb24721f86f8b8f9c697a36eb97ec3
96cb0a2fed10552c5770a45a2d6523b47ac3e38928b4a9c698d8577451182dcd
c1ccc(CN2CCNCC2)cc1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[Cl;D1;H0:4].[C;D1;H3:5]-[C:6]1-[C:7]-[#7:8]-[C:9]-[C:10]-[NH;D2;+0:11]-1>>[C;D1;H3:5]-[C:6]1-[C:7]-[#7:8]-[C:9]-[C:10]-[N;H0;D3;+0:11]-1-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[Cl;D1;H0:4]
null
[]
0
CELSIUS
2
HOUR
To a solution of (3R)-1-(4-fluoro-benzyl)-3-methyl-piperazine (3 g, 14.4 mmol) in dichloromethane (40 mL) was added triethylamine (2.0 mL, 14.4 mmol). The reaction was cooled to 0° C. and chloroacetyl chloride was added (1.1 mL, 14.4 mmol). The reaction was allowed to warm to ambient temperature and stirred for 2 hours...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Secondary amine
Tertiary amide
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1.c1ccccc1
HCl
ClCCl
0
2
C[C@@H]1CN(Cc2ccc(F)cc2)CCN1.O=C(Cl)CCl>ClCCl>C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)CCl
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-12b92824c8e24178912e292742904661
C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)CCl.O=[N+]([O-])c1cc(Cl)ccc1O>>C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1[N+](=O)[O-]
ClCC(=O)N1[C@@H](CN(CC1)CC1=CC=C(C=C1)F)C.ClC1=CC(=C(C=C1)O)[N+](=O)[O-].C([O-])([O-])=O.[K+].[K+].[I-].[K+]>>ClC1=CC(=C(OCC(=O)N2[C@@H](CN(CC2)CC2=CC=C(C=C2)F)C)C=C1)[N+](=O)[O-]
Cl[CH2:18][C:16]([N:15]1[C@H:2]([CH3:1])[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)[CH2:13][CH2:14]1)=[O:17].[OH:19][c:20]1[cH:21][cH:22][c:23]([Cl:24])[cH:25][c:26]1[N+:27](=[O:28])[O-:29]>>[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)[CH2:13][CH2:14][N:15]...
C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)CCl.O=[N+]([O-])c1cc(Cl)ccc1O
C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1[N+](=O)[O-]
null
null
CC(CC)=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
Cl-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#7:4](-[C:5])-[C:6].[OH;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[C:5]-[#7:4](-[C:2](=[O;D1;H0:3])-[CH2;D2;+0:1]-[O;H0;D2;+0:7]-[c:8](:[c:9]):[c:10])-[C:6]
94.8
[{"value": 94.8, "product": "ClC1=CC(=C(OCC(=O)N2[C@@H](CN(CC2)CC2=CC=C(C=C2)F)C)C=C1)[N+](=O)[O-]", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of 2-chloro-1-[4-(4-fluoro-benzyl)-(2R)-2-methyl-piperazin-1-yl]-ethanone (0.40 g, 1.4 mmol) in 2-butanone (14 mL) was added 4-chloro-2-nitro-phenol (0.25 g, 1.4 mmol), potassium carbonate (0.39 g, 2.8 mmol) and potassium iodide (233 mg, 1.4 mmol). The reaction was refluxed overnight, cooled and concentra...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1
HCl
CC(CC)=O
null
null
C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)CCl.O=[N+]([O-])c1cc(Cl)ccc1O>CC(CC)=O>C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1[N+](=O)[O-]
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-72a368a4f648413cbbab05cee7b6819b
C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1[N+](=O)[O-]>>C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1N
ClC1=CC(=C(OCC(=O)N2[C@@H](CN(CC2)CC2=CC=C(C=C2)F)C)C=C1)[N+](=O)[O-].[H][H]>>NC1=C(OCC(=O)N2[C@@H](CN(CC2)CC2=CC=C(C=C2)F)C)C=CC(=C1)Cl
O=[N+:27]([O-])[c:26]1[c:20]([O:19][CH2:18][C:16]([N:15]2[C@H:2]([CH3:1])[CH2:3][N:4]([CH2:5][c:6]3[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]3)[CH2:13][CH2:14]2)=[O:17])[cH:21][cH:22][c:23]([Cl:24])[cH:25]1>>[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)[CH2:13][CH2:14][N:15]1[C:16](=[...
C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1[N+](=O)[O-]
C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1N
null
[Pt](=O)=O
C(C)O
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
82.4
[{"value": 82.4, "product": "NC1=C(OCC(=O)N2[C@@H](CN(CC2)CC2=CC=C(C=C2)F)C)C=CC(=C1)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of 2-(4-chloro-2-nitro-phenoxy)-1-[4-(4-fluoro-benzyl)-(2R)-2-methyl-piperazin-1-yl]-ethanone (0.55 g, 1.3 mmol) in ethanol (25 mL) was added platinum dioxide on carbon (0.50 g, 5% on carbon). The reaction was subject to 35 psi hydrogen gas for 20 minutes. The reaction was then filtered through celite and...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1
Other
[Pt](=O)=O.C(C)O
null
null
C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1[N+](=O)[O-]>[Pt](=O)=O.C(C)O>C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1N
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-cfd19eb5d2bc4c8bbfbf484c02e6d7bb
C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1N.O=C(Cl)Oc1ccc([N+](=O)[O-])cc1>>C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1NC(=O)Oc1ccc([N+](=O)[O-])cc1
NC1=C(OCC(=O)N2[C@@H](CN(CC2)CC2=CC=C(C=C2)F)C)C=CC(=C1)Cl.N1=CC=CC=C1.ClC(=O)OC1=CC=C(C=C1)[N+](=O)[O-]>>[N+](=O)([O-])C1=CC=C(C=C1)OC(NC1=C(C=CC(=C1)Cl)OCC(=O)N1[C@@H](CN(CC1)CC1=CC=C(C=C1)F)C)=O
[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)[CH2:13][CH2:14][N:15]1[C:16](=[O:17])[CH2:18][O:19][c:20]1[cH:21][cH:22][c:23]([Cl:24])[cH:25][c:26]1[NH2:27].Cl[C:28](=[O:29])[O:30][c:31]1[cH:32][cH:33][c:34]([N+:35](=[O:36])[O-:37])[cH:38][cH:39]1>>[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:...
C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1N.O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1NC(=O)Oc1ccc([N+](=O)[O-])cc1
null
null
ClCCl
Protection
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
038720aa61a7efa0f2a9ee6f2e0adf63a9ffdc2be4697c11a6215baef34f97b2
205f353513ce9506ab61831799da8fb73ec2ef5cfa927664496d3ce72c438860
O=C(Nc1ccccc1OCC(=O)N1CCN(Cc2ccccc2)CC1)Oc1ccccc1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[c:4].[NH2;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[#8:3]-[c:4])-[NH;D2;+0:5]-[c:6](:[c:7]):[c:8]
99.7
[{"value": 99.7, "product": "[N+](=O)([O-])C1=CC=C(C=C1)OC(NC1=C(C=CC(=C1)Cl)OCC(=O)N1[C@@H](CN(CC1)CC1=CC=C(C=C1)F)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
To a solution of 2-(2-amino-4-chloro-phenoxy)-1-[4-(4-fluoro-benzyl)-(2R)-2-methyl-piperazin-1-yl]-ethanone (0.14 g, 0.36 mmol) in dichloromethane (5 mL) was added pyridine (0.032 mL, 0.39 mmol) and 4-nitrophenyl chloroformate (0.079 g, 0.39 mmol). The reaction was stirred at ambient temperature for one hour and concen...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Ether.Primary amine
Carbamic ester
null
null
C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1.c1ccccc1
HCl
ClCCl
null
1
C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1N.O=C(Cl)Oc1ccc([N+](=O)[O-])cc1>ClCCl>C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1NC(=O)Oc1ccc([N+](=O)[O-])cc1
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-7f71fd0844e740eab34efa62eff663d6
COC(=O)CCN.C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1NC(=O)Oc1ccc([N+](=O)[O-])cc1>>COC(=O)CCNC(=O)Nc1cc(Cl)ccc1OCC(=O)N1CCN(Cc2ccc(F)cc2)C[C@H]1C
[N+](=O)([O-])C1=CC=C(C=C1)OC(NC1=C(C=CC(=C1)Cl)OCC(=O)N1[C@@H](CN(CC1)CC1=CC=C(C=C1)F)C)=O.Cl.COC(CCN)=O.C(C)N(CC)CC>>COC(CCNC(=O)NC1=C(C=CC(=C1)Cl)OCC(=O)N1[C@@H](CN(CC1)CC1=CC=C(C=C1)F)C)=O
[CH3:1][O:2][C:3](=[O:4])[CH2:5][CH2:6][NH2:7].O=[N+]([O-])c1ccc(O[C:8](=[O:9])[NH:10][c:11]2[cH:12][c:13]([Cl:14])[cH:15][cH:16][c:17]2[O:18][CH2:19][C:20](=[O:21])[N:22]2[CH2:23][CH2:24][N:25]([CH2:26][c:27]3[cH:28][cH:29][c:30]([F:31])[cH:32][cH:33]3)[CH2:34][C@H:35]2[CH3:36])cc1>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][CH...
COC(=O)CCN.C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1NC(=O)Oc1ccc([N+](=O)[O-])cc1
COC(=O)CCNC(=O)Nc1cc(Cl)ccc1OCC(=O)N1CCN(Cc2ccc(F)cc2)C[C@H]1C
null
null
CO
Acylation
OtherReaction
dd3b9a4695237168f6d34c716b0d8ecc0b7dab5f3656c298943f9410474c8d9b
5fa2a2a7e6cfabf5985397b87c657557cf5ccf660b3e3b63891b8b721891cd49
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
O=[N+](-[O-])-c1:c:c:c(-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#7:3]-[c:4]):c:c:1.[#8:5]-[C:6](=[O;D1;H0:7])-[C:8]-[C:9]-[NH2;D1;+0:10]>>[#8:5]-[C:6](=[O;D1;H0:7])-[C:8]-[C:9]-[NH;D2;+0:10]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#7:3]-[c:4]
80
[{"value": 80.0, "product": "COC(CCNC(=O)NC1=C(C=CC(=C1)Cl)OCC(=O)N1[C@@H](CN(CC1)CC1=CC=C(C=C1)F)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
To a solution of (5-chloro-2-{2-[4-(4-fluoro-benzyl)-(2R)-2-methyl-piperazin-1-yl]-2-oxo-ethoxy}-phenyl)-carbamic acid 4-nitro-phenyl ester (0.10 g, 0.18 mmol) in methanol was added β-alanine methyl ester hydrochloride (0.038 g, 0.27 mmol) and triethylamine (0.038 mL, 0.27 mmol). The reaction was stirred at ambient tem...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Nitro group.Primary amine
Urea
c1ccccc1
null
c1ccccc1.C1C[NH]CC[NH]1.c1ccccc1
HO-
CO
null
8
COC(=O)CCN.C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1NC(=O)Oc1ccc([N+](=O)[O-])cc1>CO>COC(=O)CCNC(=O)Nc1cc(Cl)ccc1OCC(=O)N1CCN(Cc2ccc(F)cc2)C[C@H]1C
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-f75693f6867e4644b7b4bb511c63c3fc
COC(=O)CCNC(=O)Nc1cc(Cl)ccc1OCC(=O)N1CCN(Cc2ccc(F)cc2)C[C@H]1C>>C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1NC(=O)NCCC(=O)O
COC(CCNC(=O)NC1=C(C=CC(=C1)Cl)OCC(=O)N1[C@@H](CN(CC1)CC1=CC=C(C=C1)F)C)=O.O.[OH-].[Li+]>>ClC=1C=CC(=C(C1)NC(NCCC(=O)O)=O)OCC(=O)N1[C@@H](CN(CC1)CC1=CC=C(C=C1)F)C
C[O:35][C:33]([CH2:32][CH2:31][NH:30][C:28]([NH:27][c:26]1[c:20]([O:19][CH2:18][C:16]([N:15]2[C@H:2]([CH3:1])[CH2:3][N:4]([CH2:5][c:6]3[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]3)[CH2:13][CH2:14]2)=[O:17])[cH:21][cH:22][c:23]([Cl:24])[cH:25]1)=[O:29])=[O:34]>>[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:...
COC(=O)CCNC(=O)Nc1cc(Cl)ccc1OCC(=O)N1CCN(Cc2ccc(F)cc2)C[C@H]1C
C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1NC(=O)NCCC(=O)O
null
null
CO.O.O1CCCC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
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 a solution of 3-[3-(5-chloro-2-{2-[4-(4-fluoro-benzyl)-(2R)-2-methyl-piperazin-1-yl]-2-oxo-ethoxy}-phenyl)-ureido]-propionic acid methyl ester (0.057 g, 0.11 mmol) in tetrahydrofuran (3 mL), methanol (3 mL) and water (1 mL) was added lithium hydroxide monohydrate (0.023 g, 0.55 mmol). The reaction was stirred at amb...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1
Other
CO.O.O1CCCC1
null
8
COC(=O)CCNC(=O)Nc1cc(Cl)ccc1OCC(=O)N1CCN(Cc2ccc(F)cc2)C[C@H]1C>CO.O.O1CCCC1>C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1NC(=O)NCCC(=O)O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-560be2081f054067815e1cc2c2faf8c2
C[C@@H]1CN[C@@H](C)CN1Cc1ccc(F)cc1.O=C(Cl)CCl>>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)CCl
ClCC(=O)Cl.FC1=CC=C(CN2[C@@H](CN[C@H](C2)C)C)C=C1.C(C)N(CC)CC>>ClCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C
[CH3:1][C@@H:2]1[CH2:3][NH:16][C@@H:13]([CH3:14])[CH2:15][N:4]1[CH2:5][c:6]1[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]1.Cl[C:17](=[O:18])[CH2:19][Cl:20]>>[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)[C@@H:13]([CH3:14])[CH2:15][N:16]1[C:17](=[O:18])[CH2:19][Cl:20]
C[C@@H]1CN[C@@H](C)CN1Cc1ccc(F)cc1.O=C(Cl)CCl
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)CCl
null
null
ClCCl
Acylation
N-alkylation of secondary amines with alkyl halides
949c19544298d3876f7b0458b2280abace43b4774b9d92cfdfa0edf7e77056ba
33bbcee2d30fd19070312c9da89cbcd21bc5c4bdf302b8e5117d0cbfbe912965
c1ccc(CN2CCNCC2)cc1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[Cl;D1;H0:4].[C;D1;H3:5]-[C@H;D3;+0:6]1-[CH2;D2;+0:7]-[N;H0;D3;+0:8](-[C:9]-[c:10])-[C@H;D3;+0:11](-[C;D1;H3:12])-[CH2;D2;+0:13]-[NH;D2;+0:14]-1>>[C;D1;H3:5]-[C@H;D3;+0:6]1-[CH2;D2;+0:7]-[N;H0;D3;+0:14](-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[Cl;D1;H0:4])-[C@H;D3;+0:11](-[C;D1;H3:12])...
84.9
[{"value": 84.9, "product": "ClCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
To a solution of (2R,5S)-1-(4-fluoro-benzyl)-2,5-dimethyl-piperazine (2.5 g, 11.2 mmol) in dry dichloromethane (11 mL) at 0° C. was added triethylamine (1.57 mL, 11.2 mmol) followed by chloroacetyl chloride (0.86 mL, 11.2 mmol). The resulting reaction mixture was stirred for 30 minutes. The reaction was then filtered t...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Secondary amine.Tertiary amine
Tertiary amide.Tertiary amine
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1.c1ccccc1
HCl
ClCCl
null
0.5
C[C@@H]1CN[C@@H](C)CN1Cc1ccc(F)cc1.O=C(Cl)CCl>ClCCl>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)CCl
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-25061445411d408e8604d629580259c9
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)CCl.O=[N+]([O-])c1cc(Cl)ccc1O>>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1[N+](=O)[O-]
ClCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C.[N+](=O)([O-])C1=C(C=CC(=C1)Cl)O.C([O-])([O-])=O.[K+].[K+].[I-].[K+]>>ClC1=CC(=C(OCC(=O)N2[C@@H](CN([C@H](C2)C)CC2=CC=C(C=C2)F)C)C=C1)[N+](=O)[O-]
Cl[CH2:19][C:17]([N:16]1[C@H:2]([CH3:1])[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)[C@@H:13]([CH3:14])[CH2:15]1)=[O:18].[OH:20][c:21]1[cH:22][cH:23][c:24]([Cl:25])[cH:26][c:27]1[N+:28](=[O:29])[O-:30]>>[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)[C@@H:13]([...
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)CCl.O=[N+]([O-])c1cc(Cl)ccc1O
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1[N+](=O)[O-]
null
null
CC(CC)=O.O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
Cl-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#7:4](-[C:5])-[C:6].[OH;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[C:5]-[#7:4](-[C:2](=[O;D1;H0:3])-[CH2;D2;+0:1]-[O;H0;D2;+0:7]-[c:8](:[c:9]):[c:10])-[C:6]
92.5
[{"value": 92.5, "product": "ClC1=CC(=C(OCC(=O)N2[C@@H](CN([C@H](C2)C)CC2=CC=C(C=C2)F)C)C=C1)[N+](=O)[O-]", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of 2-chloro-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone (1.0 g, 3.35 mmol) in butanone (35 mL) was added 2-nitro-4-chlorophenol (0.64 g, 3.69 mmol), potassium carbonate (0.93 g, 6.7mmol) and potassium iodide (0.56 g, 3.35 mmol). The reaction mixture was heated at reflux overnight....
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1
HCl
CC(CC)=O.O
null
null
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)CCl.O=[N+]([O-])c1cc(Cl)ccc1O>CC(CC)=O.O>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1[N+](=O)[O-]
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-b2050dd585794dadb81d98c2170cc5a9
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1[N+](=O)[O-]>>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1N
ClC1=CC(=C(OCC(=O)N2[C@@H](CN([C@H](C2)C)CC2=CC=C(C=C2)F)C)C=C1)[N+](=O)[O-].[H][H]>>NC1=C(OCC(=O)N2[C@@H](CN([C@H](C2)C)CC2=CC=C(C=C2)F)C)C=CC(=C1)Cl
O=[N+:28]([O-])[c:27]1[c:21]([O:20][CH2:19][C:17]([N:16]2[C@H:2]([CH3:1])[CH2:3][N:4]([CH2:5][c:6]3[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]3)[C@@H:13]([CH3:14])[CH2:15]2)=[O:18])[cH:22][cH:23][c:24]([Cl:25])[cH:26]1>>[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)[C@@H:13]([CH3:14])[C...
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1[N+](=O)[O-]
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1N
null
[Pt]
C(C)O
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
69.3
[{"value": 69.3, "product": "NC1=C(OCC(=O)N2[C@@H](CN([C@H](C2)C)CC2=CC=C(C=C2)F)C)C=CC(=C1)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of 2-(4-chloro-2-nitro-phenoxy)-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone (2.2 g, 5.05 mmol) in ethanol (50 mL) in a par bottle was added 5% platinum on carbon (2.2 g). The reaction mixture was subjected to hydrogen gas (35 psi) for 30 minutes. The reaction mixture was filtered ...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1
Other
[Pt].C(C)O
null
null
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1[N+](=O)[O-]>[Pt].C(C)O>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1N
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-51ce9bb9875247e18ea225cd6ad21a82
CCOC(=O)CS(=O)(=O)Cl.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1N>>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1NS(=O)(=O)CC(=O)O
O.[OH-].[Li+].NC1=C(OCC(=O)N2[C@@H](CN([C@H](C2)C)CC2=CC=C(C=C2)F)C)C=CC(=C1)Cl.C([O-])([O-])=O.[K+].[K+].C(C)OC(CS(=O)(=O)Cl)=O.CN(C)C1=NC=CC=C1>>ClC=1C=CC(=C(C1)NS(=O)(=O)CC(=O)O)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C
CC[O:35][C:33]([CH2:32][S:29](Cl)(=[O:30])=[O:31])=[O:34].[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)[C@@H:13]([CH3:14])[CH2:15][N:16]1[C:17](=[O:18])[CH2:19][O:20][c:21]1[cH:22][cH:23][c:24]([Cl:25])[cH:26][c:27]1[NH2:28]>>[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c...
CCOC(=O)CS(=O)(=O)Cl.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1N
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1NS(=O)(=O)CC(=O)O
null
null
CN(C=O)C.O.C(C)(=O)OCC
Acylation
OtherReaction
cbfd6f28b9d0b9d94f7e4648596955340b078b671cf962c5f2f1350eb0523981
856cd572bbc6c063d7e2e7d418946e4ec910f62888e2087856bb7fd393157377
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[C:4]-[S;H0;D4;+0:5](-Cl)(=[O;D1;H0:6])=[O;D1;H0:7].[NH2;D1;+0:8]-[c:9](:[c:10]):[c:11]>>[O;D1;H0:6]=[S;H0;D4;+0:5](=[O;D1;H0:7])(-[C:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1])-[NH;D2;+0:8]-[c:9](:[c:10]):[c:11]
null
[]
null
null
null
null
To a solution of 2-(2-amino-4-chloro-phenoxy)-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone (0.030 g, 0.074 mmol) in dimethylformamide (0.5 ml) was added potassium carbonate (0.030 g, 0.239 mmol), chlorosulfonyl-acetic acid ethyl ester (0.02 g, 0.12 mmol) (for preparation, see: Helv. Chim. Acta.,...
10.6084/m9.figshare.5104873.v1
null
Ester.Primary amine.Sulfonyl halide
Sulfonamide.Carboxylic acid
null
null
C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1
HCl
CN(C=O)C.O.C(C)(=O)OCC
null
null
CCOC(=O)CS(=O)(=O)Cl.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1N>CN(C=O)C.O.C(C)(=O)OCC>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1NS(=O)(=O)CC(=O)O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-505cb70f068b4b7f89454fbc2fbe49c7
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)CCl.O=Cc1cc(Cl)ccc1O>>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1C=O
ClCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C.ClC1=CC=C(C(C=O)=C1)O.C([O-])([O-])=O.[K+].[K+].[I-].[K+]>>ClC=1C=CC(=C(C=O)C1)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C
Cl[CH2:19][C:17]([N:16]1[C@H:2]([CH3:1])[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)[C@@H:13]([CH3:14])[CH2:15]1)=[O:18].[OH:20][c:21]1[cH:22][cH:23][c:24]([Cl:25])[cH:26][c:27]1[CH:28]=[O:29]>>[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)[C@@H:13]([CH3:14])[...
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)CCl.O=Cc1cc(Cl)ccc1O
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1C=O
null
null
CN(C=O)C.[Cl-].[Na+].O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
Cl-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#7:4](-[C:5])-[C:6].[O;D1;H0:7]=[C:8]-[c:9]:[c:10](-[OH;D1;+0:11]):[c:12]>>[C:5]-[#7:4](-[C:2](=[O;D1;H0:3])-[CH2;D2;+0:1]-[O;H0;D2;+0:11]-[c:10](:[c:12]):[c:9]-[C:8]=[O;D1;H0:7])-[C:6]
84.5
[{"value": 84.5, "product": "ClC=1C=CC(=C(C=O)C1)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
null
null
To a solution of 2-chloro-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone (2.87 g, 9.6 mmol) in dimethylformamide (20 mL) was added 5-chlorosalicylaldehyde (1.65 g, 10.5 mmol), potassium carbonate (2.64 g, 19.2 mmol) and potassium iodide (1.59 g, 9.6 mmol). The resulting mixture was heated to 100° ...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1
HCl
CN(C=O)C.[Cl-].[Na+].O
100
null
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)CCl.O=Cc1cc(Cl)ccc1O>CN(C=O)C.[Cl-].[Na+].O>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1C=O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-bc7c522e78254b1bac83549a81ef66f7
COC(=O)CCN.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1C=O>>COC(=O)CCNCc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
C(#N)[BH3-].[Na+].ClC=1C=CC(=C(C=O)C1)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C.Cl.COC(CCN)=O>>COC(CCNCC1=C(C=CC(=C1)Cl)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C)=O
[CH3:1][O:2][C:3](=[O:4])[CH2:5][CH2:6][NH2:7].O=[CH:8][c:9]1[cH:10][c:11]([Cl:12])[cH:13][cH:14][c:15]1[O:16][CH2:17][C:18](=[O:19])[N:20]1[CH2:21][C@H:22]([CH3:23])[N:24]([CH2:25][c:26]2[cH:27][cH:28][c:29]([F:30])[cH:31][cH:32]2)[CH2:33][C@H:34]1[CH3:35]>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][CH2:6][NH:7][CH2:8][c:9]1[cH...
COC(=O)CCN.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1C=O
COC(=O)CCNCc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
null
null
C(C)(=O)O.CO.C(C)(=O)OCC.C(C)N(CC)CC
Heteroatom Alkylation and Arylation
Reductive amination with aldehyde
422be648aea52bce28ccc8fb32ec3178aaa47bbd624f063874619362f075b5f2
7915721a3e395aed85e3c40dc4d725c571a931ac517c6a0da16f2a2b0bb5eac7
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
O=[CH;D2;+0:1]-[c:2](:[c:3]):[c:4].[#8:5]-[C:6](=[O;D1;H0:7])-[C:8]-[C:9]-[NH2;D1;+0:10]>>[#8:5]-[C:6](=[O;D1;H0:7])-[C:8]-[C:9]-[NH;D2;+0:10]-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4]
38.4
[{"value": 38.4, "product": "COC(CCNCC1=C(C=CC(=C1)Cl)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
To a solution of 5-chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-benzaldehyde (0.075 g, 0.18 mmol) in methanol (2 mL) was added 3-amino-propionic acid methyl ester hydrochloride salt (0.063 g, 0.45 mmol) and the pH of the solution was adjusted to 5–6 with triethylamine and acetic a...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Primary amine
Secondary amine
null
null
c1ccccc1.C1C[NH]CC[NH]1.c1ccccc1
Other
C(C)(=O)O.CO.C(C)(=O)OCC.C(C)N(CC)CC
null
1
COC(=O)CCN.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1C=O>C(C)(=O)O.CO.C(C)(=O)OCC.C(C)N(CC)CC>COC(=O)CCNCc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-622432d3bf8e4e35b4337c9306449914
COC(=O)CCNCc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C>>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CNCCC(=O)O
COC(CCNCC1=C(C=CC(=C1)Cl)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C)=O.O.[OH-].[Li+]>>ClC=1C=CC(=C(CNCCC(=O)O)C1)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C
C[O:34][C:32]([CH2:31][CH2:30][NH:29][CH2:28][c:27]1[c:21]([O:20][CH2:19][C:17]([N:16]2[C@H:2]([CH3:1])[CH2:3][N:4]([CH2:5][c:6]3[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]3)[C@@H:13]([CH3:14])[CH2:15]2)=[O:18])[cH:22][cH:23][c:24]([Cl:25])[cH:26]1)=[O:33]>>[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10]...
COC(=O)CCNCc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CNCCC(=O)O
null
null
CO.O.O1CCCC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
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 a solution of 3-(5-chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-benzylamino)-propionic acid methyl ester (0.035 g, 0.069 mmol) in tetrahydrofuran (0.2 mL), methanol (0.2 mL) and water (0.1 mL) was added lithium hydroxide monohydrate (0.015 g, 0.35 mmol). The reaction mixture wa...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1
Other
CO.O.O1CCCC1
null
8
COC(=O)CCNCc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C>CO.O.O1CCCC1>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CNCCC(=O)O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-e670c84d8b25493984d67a7d7e5b877b
NC(=O)c1cccc(CCl)c1C(N)=O.Oc1ccc(Cl)cc1>>O=C1c2ccccc2C(=O)N1Cc1cc(Cl)ccc1O
ClC1=CC=C(C=C1)O.ClCC1=C(C(C(=O)N)=CC=C1)C(=O)N.CO>>ClC=1C=CC(=C(CN2C(C3=CC=CC=C3C2=O)=O)C1)O
N[C:9]([c:8]1[c:3]([C:2](=[O:1])[NH2:11])[c:4]([CH2:12]Cl)[cH:5][cH:6][cH:7]1)=[O:10].[cH:13]1[cH:14][c:15]([Cl:16])[cH:17][cH:18][c:19]1[OH:20]>>[O:1]=[C:2]1[c:3]2[cH:4][cH:5][cH:6][cH:7][c:8]2[C:9](=[O:10])[N:11]1[CH2:12][c:13]1[cH:14][c:15]([Cl:16])[cH:17][cH:18][c:19]1[OH:20]
NC(=O)c1cccc(CCl)c1C(N)=O.Oc1ccc(Cl)cc1
O=C1c2ccccc2C(=O)N1Cc1cc(Cl)ccc1O
null
[Cl-].[Zn+2].[Cl-]
null
Acylation
OtherReaction
73e4de8720adaa306cfce637e1b8579a9dd4dd28c86d9933455a9545c9033513
d409ff325fafc88481d814a49cb90e56150b5ec0f94fa64b291dbf1c8c89c364
O=C1c2ccccc2C(=O)N1Cc1ccccc1
Cl-[CH2;D2;+0:1]-[c;H0;D3;+0:2]1:[c:3]:[c:4]:[c:5]:[c:6](-[C;H0;D3;+0:7](-N)=[O;D1;H0:8]):[c:9]:1-[C:10](-[NH2;D1;+0:11])=[O;D1;H0:12].[O;D1;H1:13]-[c:14](:[c:15]):[cH;D2;+0:16]:[c:17]:[c:18]>>[O;D1;H0:8]=[C;H0;D3;+0:7]1-[N;H0;D3;+0:11](-[CH2;D2;+0:1]-[c;H0;D3;+0:16](:[c:17]:[c:18]):[c:14](-[O;D1;H1:13]):[c:15])-[C:10]...
null
[]
90
CELSIUS
48
HOUR
To 4-chlorophenol (2.0 g, 15.5 mmol) and chloromethylphthalamide (2.62 g, 13.4 mmol) was added zinc chloride (3 mL, 0.5 M in tetrahydrofuran, 1.5 mmol). The reaction was stirred at 90° C. for 48 hours. After cooling the reaction was diluted with methanol (15 mL) and brought to reflux. After 30 minutes the hot suspensio...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Primary amide.Primary amide
Substituted dicarboximide
c1ccccc1.c1ccccc1
c1ccc2c(c1)C[NH]C2.c1ccccc1
c1ccc2c(c1)C[NH]C2.c1ccccc1
HCl
[Cl-].[Zn+2].[Cl-]
90
48
NC(=O)c1cccc(CCl)c1C(N)=O.Oc1ccc(Cl)cc1>[Cl-].[Zn+2].[Cl-]>O=C1c2ccccc2C(=O)N1Cc1cc(Cl)ccc1O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-48c9e93d53b0453aa0a8c08da1bd324d
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)CCl.O=C1c2ccccc2C(=O)N1Cc1cc(Cl)ccc1O>>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CN1C(=O)c2ccccc2C1=O
ClCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C.[I-].[K+].ClC=1C=CC(=C(CN2C(C3=CC=CC=C3C2=O)=O)C1)O.C([O-])([O-])=O.[K+].[K+]>>ClC=1C=CC(=C(CN2C(C3=CC=CC=C3C2=O)=O)C1)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C
Cl[CH2:19][C:17]([N:16]1[C@H:2]([CH3:1])[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)[C@@H:13]([CH3:14])[CH2:15]1)=[O:18].[OH:20][c:21]1[cH:22][cH:23][c:24]([Cl:25])[cH:26][c:27]1[CH2:28][N:29]1[C:30](=[O:31])[c:32]2[cH:33][cH:34][cH:35][cH:36][c:37]2[C:38]1=[O:39]>>[CH3:1][C@@H:2]1[CH2:3][N:4]([C...
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)CCl.O=C1c2ccccc2C(=O)N1Cc1cc(Cl)ccc1O
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CN1C(=O)c2ccccc2C1=O
null
null
O.CN(C=O)C
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
O=C(COc1ccccc1CN1C(=O)c2ccccc2C1=O)N1CCN(Cc2ccccc2)CC1
Cl-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#7:4](-[C:5])-[C:6].[OH;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[C:5]-[#7:4](-[C:2](=[O;D1;H0:3])-[CH2;D2;+0:1]-[O;H0;D2;+0:7]-[c:8](:[c:9]):[c:10])-[C:6]
63.3
[{"value": 63.3, "product": "ClC=1C=CC(=C(CN2C(C3=CC=CC=C3C2=O)=O)C1)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
70
CELSIUS
null
null
To a solution of 2-chloro-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone (0.75 g, 2.50 mmol) in dry dimethylformamide (25 mL) was added potassium iodide (0.40 g, 2.39 mmol), 2-(5-chloro-2-hydroxy-benzyl)-isoindole-1,3-dione (0.80 g, 2.76 mmol) and potassium carbonate (0.70 g, 5.10 mmol). The resul...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1.c1ccc2c(c1)C[NH]C2
HCl
O.CN(C=O)C
70
null
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)CCl.O=C1c2ccccc2C(=O)N1Cc1cc(Cl)ccc1O>O.CN(C=O)C>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CN1C(=O)c2ccccc2C1=O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-3e772f25c01b4b32b32b3bd235b01aab
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CN1C(=O)c2ccccc2C1=O>>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CN
ClC=1C=CC(=C(CN2C(C3=CC=CC=C3C2=O)=O)C1)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C.NN>>NCC1=C(OCC(=O)N2[C@@H](CN([C@H](C2)C)CC2=CC=C(C=C2)F)C)C=CC(=C1)Cl
O=C1c2ccccc2C(=O)[N:29]1[CH2:28][c:27]1[c:21]([O:20][CH2:19][C:17]([N:16]2[C@H:2]([CH3:1])[CH2:3][N:4]([CH2:5][c:6]3[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]3)[C@@H:13]([CH3:14])[CH2:15]2)=[O:18])[cH:22][cH:23][c:24]([Cl:25])[cH:26]1>>[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)[C@@...
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CN1C(=O)c2ccccc2C1=O
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CN
null
null
C(C)O
Reduction
Phthalimide deprotection
d9f63cee80ef758bd939ff2a10772447b3092f1576180488281833a98eb1691a
dbfe4201a9328005dfaec4c3f363ddbb4ef3c9b825f648735dc97b2b57396333
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
O=C1-[N;H0;D3;+0:1](-[C:2]-[c:3])-C(=O)-c2:c:c:c:c:c:2-1>>[NH2;D1;+0:1]-[C:2]-[c:3]
null
[]
null
null
17
HOUR
To 2-(5-chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-benzyl)-isoindole-1,3-dione (0.87 g, 1.59 mmol) in ethanol (20 mL) was added 35% hydrazine (3 mL, 33.1 mmol). After 17 hours, the reaction was filtered and concentrated to a tan solid. This solid was triturated with methylene ch...
10.6084/m9.figshare.5104873.v1
null
Substituted dicarboximide
Primary amine
c1ccc2c(c1)C[NH]C2
null
C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1
HO-
C(C)O
null
17
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CN1C(=O)c2ccccc2C1=O>C(C)O>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CN
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-23074664ee454d3abe3137f8c295aaf7
CCOC(=O)C(C)S(=O)(=O)Cl.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CN>>CC(C(=O)O)S(=O)(=O)NCc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
C(C)OC(C(C)S(=O)(=O)Cl)=O.NCC1=C(OCC(=O)N2[C@@H](CN([C@H](C2)C)CC2=CC=C(C=C2)F)C)C=CC(=C1)Cl.C(C)N(CC)CC.CN(C)C1=NC=CC=C1>>ClC=1C=CC(=C(CNS(=O)(=O)C(C(=O)O)C)C1)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C
CC[O:5][C:3]([CH:2]([CH3:1])[S:6](Cl)(=[O:7])=[O:8])=[O:4].[NH2:9][CH2:10][c:11]1[cH:12][c:13]([Cl:14])[cH:15][cH:16][c:17]1[O:18][CH2:19][C:20](=[O:21])[N:22]1[CH2:23][C@H:24]([CH3:25])[N:26]([CH2:27][c:28]2[cH:29][cH:30][c:31]([F:32])[cH:33][cH:34]2)[CH2:35][C@H:36]1[CH3:37]>>[CH3:1][CH:2]([C:3](=[O:4])[OH:5])[S:6](=...
CCOC(=O)C(C)S(=O)(=O)Cl.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CN
CC(C(=O)O)S(=O)(=O)NCc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
null
null
C(C)(=O)OCC.O1CCCC1
Miscellaneous
OtherReaction
4d74724bc142da1113df2b4e9399f96e02619849034a54fbdd3d6c71934c1f8a
f29ac8585382f8298a9dbb9cc996a0739a952f5223b9c6de8b120b7811c408d9
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[C:4](-[C;D1;H3:5])-[S;H0;D4;+0:6](-Cl)(=[O;D1;H0:7])=[O;D1;H0:8].[NH2;D1;+0:9]-[C:10]-[c:11]>>[C;D1;H3:5]-[C:4](-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1])-[S;H0;D4;+0:6](=[O;D1;H0:7])(=[O;D1;H0:8])-[NH;D2;+0:9]-[C:10]-[c:11]
null
[]
null
null
null
null
To a solution of 2-(2-aminomethyl-4-chloro-phenoxy)-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone (0.05 g, 0.119 mmol) in tetrahydrofuran (1 ml) at −40° C. was added triethylamine (0.021 ml, 0.151 mmol), catalytic dimethylaminopyridine and finally a solution of 2-chlorosulfonyl-propionic acid eth...
10.6084/m9.figshare.5104873.v1
null
Ester.Primary amine.Sulfonyl halide
Sulfonamide.Carboxylic acid
null
null
c1ccccc1.C1C[NH]CC[NH]1.c1ccccc1
HCl
C(C)(=O)OCC.O1CCCC1
null
null
CCOC(=O)C(C)S(=O)(=O)Cl.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CN>C(C)(=O)OCC.O1CCCC1>CC(C(=O)O)S(=O)(=O)NCc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-a56750f9d5d440e2bf22ef0d9a46e092
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1C=O>>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CO
[OH-].[Na+].Cl.ClC=1C=CC(=C(C=O)C1)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C.[BH4-].[Na+]>>ClC1=CC(=C(OCC(=O)N2[C@@H](CN([C@H](C2)C)CC2=CC=C(C=C2)F)C)C=C1)CO
[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)[C@@H:13]([CH3:14])[CH2:15][N:16]1[C:17](=[O:18])[CH2:19][O:20][c:21]1[cH:22][cH:23][c:24]([Cl:25])[cH:26][c:27]1[CH:28]=[O:29]>>[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)[C@@H:13]([CH3:14])[CH2:1...
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1C=O
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CO
null
null
CO
Reduction
Reduction of aldehydes and ketones to alcohols
e7895795cd3f75445716c94697823c5929dcd4b5344525875fe75d36bca2f9d7
21bb81d5469aaaca71ab12c186bea4016451717fad8780cf288858a7d8fbc55a
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
[O;H0;D1;+0:1]=[CH;D2;+0:2]-[c:3](:[c:4]):[c:5]>>[OH;D1;+0:1]-[CH2;D2;+0:2]-[c:3](:[c:4]):[c:5]
98.7
[{"value": 98.7, "product": "ClC1=CC(=C(OCC(=O)N2[C@@H](CN([C@H](C2)C)CC2=CC=C(C=C2)F)C)C=C1)CO", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of 5-chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-benzaldehyde (0.99 g, 2.36 mmol) in dry methanol (25 mL) was added sodium borohydride (0.19 g, 4.92 mmol). After 1 hour the reaction was acidified to pH 2 by the addition of 1N hydrochloric acid. After 5 minutes the r...
10.6084/m9.figshare.5104873.v1
null
Aldehyde
Primary alcohol
null
null
C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1
null
CO
null
null
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1C=O>CO>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CO
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-97b235d71bf44205a4006c9047c4a223
CC(C)(C)OC(=O)CBr.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CO>>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1COCC(=O)OC(C)(C)C
[H-].[Na+].ClC1=CC(=C(OCC(=O)N2[C@@H](CN([C@H](C2)C)CC2=CC=C(C=C2)F)C)C=C1)CO.BrCC(=O)OC(C)(C)C>>C(C)(C)(C)OC(COCC1=C(C=CC(=C1)Cl)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C)=O
Br[CH2:30][C:31](=[O:32])[O:33][C:34]([CH3:35])([CH3:36])[CH3:37].[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]2)[C@@H:13]([CH3:14])[CH2:15][N:16]1[C:17](=[O:18])[CH2:19][O:20][c:21]1[cH:22][cH:23][c:24]([Cl:25])[cH:26][c:27]1[CH2:28][OH:29]>>[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]...
CC(C)(C)OC(=O)CBr.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CO
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1COCC(=O)OC(C)(C)C
null
null
O1CCCC1
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
4541d644834c1bca555c4310180b1edadd2271c26488a32c314314a2e4f9c76f
1858e49e1dc71f5ec31a1f9e719a3d52cdbfbbd98e3e0f8a48e0f56789173453
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C:5](-[C;D1;H3:6])(-[C;D1;H3:7])-[C;D1;H3:8].[OH;D1;+0:9]-[C:10]-[c:11]>>[C;D1;H3:6]-[C:5](-[C;D1;H3:7])(-[C;D1;H3:8])-[#8:4]-[C:2](=[O;D1;H0:3])-[CH2;D2;+0:1]-[O;H0;D2;+0:9]-[C:10]-[c:11]
65.4
[{"value": 65.4, "product": "C(C)(C)(C)OC(COCC1=C(C=CC(=C1)Cl)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a 0° C. solution of sodium hydride (0.025 g, 60% dispersion, 1.0 mmol) in tetrahydrofuran (2 mL) was added a solution of 2-(4-chloro-2-hydroxymethyl-phenoxy)-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone (0.17 g, 0.40 mmol) and tert-butyl bromoacetate (0.23 g, 3.0 mmol) in tetrahydrofuran (2 m...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Primary alcohol
Ester.Ether
null
null
C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1
HBr
O1CCCC1
null
null
CC(C)(C)OC(=O)CBr.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CO>O1CCCC1>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1COCC(=O)OC(C)(C)C
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-cc2428fcedcd452c91dbdc8ef927468e
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1COCC(=O)OC(C)(C)C>>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1COCC(=O)O
Cl.C(C)(C)(C)OC(COCC1=C(C=CC(=C1)Cl)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C)=O.FC(C(=O)O)(F)F>>ClC=1C=CC(=C(COCC(=O)O)C1)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C
CC(C)(C)[O:33][C:31]([CH2:30][O:29][CH2:28][c:27]1[c:21]([O:20][CH2:19][C:17]([N:16]2[C@H:2]([CH3:1])[CH2:3][N:4]([CH2:5][c:6]3[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]3)[C@@H:13]([CH3:14])[CH2:15]2)=[O:18])[cH:22][cH:23][c:24]([Cl:25])[cH:26]1)=[O:32]>>[CH3:1][C@@H:2]1[CH2:3][N:4]([CH2:5][c:6]2[cH:7][cH:8][c:9]([F:10])[...
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1COCC(=O)OC(C)(C)C
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1COCC(=O)O
null
null
ClCCl
Deprotection
Deprotection of carboxylic acid
152e5537e48c95b4a3e767536b0f9f68d1308e5f484070828ab5ed951805157a
7f019d4cfe9b3036d0a2d3a3209aa0e1fcb05418ebee15a4be5e125d315d5f01
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
C-C(-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
8
HOUR
To a solution of (5-chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-benzyloxy)-acetic acid tert-butyl ester (0.14 g, 0.25 mmol) in dichloromethane (5.0 mL) was added trifluoroacetic acid (0.5 mL). The resulting mixture was stirred at ambient temperature overnight, diluted with dichlo...
10.6084/m9.figshare.5104873.v1
null
Ester.Boc
Carboxylic acid
null
null
C1C[NH]CC[NH]1.c1ccccc1.c1ccccc1
Other
ClCCl
null
8
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1COCC(=O)OC(C)(C)C>ClCCl>C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1COCC(=O)O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-19342639db9b4a3ba8c49da68878b3f5
CS(N)(=O)=O.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1COCC(=O)O>>CC(=O)C(OCc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C)S(N)(=O)=O
ClC=1C=CC(=C(COCC(=O)O)C1)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C.C1(CCCCC1)N=C=NC1CCCCC1.CS(=O)(=O)N>>ClC=1C=CC(=C(COC(S(=O)(=O)N)C(C)=O)C1)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C
[CH3:1][S:34]([NH2:35])(=[O:36])=[O:37].O[C:2](=[O:3])[CH2:4][O:5][CH2:6][c:7]1[cH:8][c:9]([Cl:10])[cH:11][cH:12][c:13]1[O:14][CH2:15][C:16](=[O:17])[N:18]1[CH2:19][C@H:20]([CH3:21])[N:22]([CH2:23][c:24]2[cH:25][cH:26][c:27]([F:28])[cH:29][cH:30]2)[CH2:31][C@H:32]1[CH3:33]>>[CH3:1][C:2](=[O:3])[CH:4]([O:5][CH2:6][c:7]1...
CS(N)(=O)=O.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1COCC(=O)O
CC(=O)C(OCc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C)S(N)(=O)=O
null
CN(C1=CC=NC=C1)C
ClCCl
C-C Coupling
OtherReaction
ef4c24c8618fb05ddb9f753c03d5ae07a6f763c9b659b2d73d681b8edc5ed76d
297ed2948e8a04d00e87d7fa50440f162f825b8d3e3b2ae92283e866a3596c29
O=C(COc1ccccc1)N1CCN(Cc2ccccc2)CC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[CH2;D2;+0:3]-[#8:4]-[C:5].[CH3;D1;+0:6]-[S;H0;D4;+0:7](-[N;D1;H2:8])(=[O;D1;H0:9])=[O;D1;H0:10]>>[C:5]-[#8:4]-[CH;D3;+0:3](-[C;H0;D3;+0:1](-[CH3;D1;+0:6])=[O;D1;H0:2])-[S;H0;D4;+0:7](-[N;D1;H2:8])(=[O;D1;H0:9])=[O;D1;H0:10]
36.8
[{"value": 36.8, "product": "ClC=1C=CC(=C(COC(S(=O)(=O)N)C(C)=O)C1)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
20
MINUTE
To a solution of (5-chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-benzyloxy)-acetic acid (0.11 g, 0.22 mmol) in dichloromethane (10 mL) was added 4-dimethylaminopyridine (0.04 g, 0.33 mmol) and 1,3-dicyclohexylcarbodiimide (0.049 g, 0.24 mmol). The resulting reaction mixture was st...
10.6084/m9.figshare.5104873.v1
null
Sulfonamide.Carboxylic acid.Ether
Sulfonamide.Ketone
null
null
c1ccccc1.C1C[NH]CC[NH]1.c1ccccc1
HO-
CN(C1=CC=NC=C1)C.ClCCl
null
0.333333
CS(N)(=O)=O.C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1COCC(=O)O>CN(C1=CC=NC=C1)C.ClCCl>CC(=O)C(OCc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C)S(N)(=O)=O
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-3c0eb05c8a254cc7ada9c39c6c9c73e0
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CO.Cc1ccccc1S(=O)(=O)N=C=O>>Cc1ccccc1S(=O)(=O)NC(=O)OCc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
C=1(C(=CC=CC1)S(=O)(=O)N=C=O)C.ClC1=CC(=C(OCC(=O)N2[C@@H](CN([C@H](C2)C)CC2=CC=C(C=C2)F)C)C=C1)CO.C(C)N(CC)CC>>ClC=1C=CC(=C(COC(NS(=O)(=O)C2=C(C=CC=C2)C)=O)C1)OCC(=O)N1[C@@H](CN([C@H](C1)C)CC1=CC=C(C=C1)F)C
[OH:14][CH2:15][c:16]1[cH:17][c:18]([Cl:19])[cH:20][cH:21][c:22]1[O:23][CH2:24][C:25](=[O:26])[N:27]1[CH2:28][C@H:29]([CH3:30])[N:31]([CH2:32][c:33]2[cH:34][cH:35][c:36]([F:37])[cH:38][cH:39]2)[CH2:40][C@H:41]1[CH3:42].[CH3:1][c:2]1[cH:3][cH:4][cH:5][cH:6][c:7]1[S:8](=[O:9])(=[O:10])[N:11]=[C:12]=[O:13]>>[CH3:1][c:2]1[...
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CO.Cc1ccccc1S(=O)(=O)N=C=O
Cc1ccccc1S(=O)(=O)NC(=O)OCc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
null
CN(C1=CC=NC=C1)C
C1(=CC=CC=C1)C
Protection
OtherReaction
5903472f7fde872c0e2c01c89ed6188579dca0b618d750fc8f4727ce6f8df9e4
9b07b5c64086b5fa83ceb215f711b596c3e070d0d9c870e61dc7f6592ff6725e
O=C(NS(=O)(=O)c1ccccc1)OCc1ccccc1OCC(=O)N1CCN(Cc2ccccc2)CC1
[O;D1;H0:1]=[#16:2](=[O;D1;H0:3])(-[c:4])-[N;H0;D2;+0:5]=[C;H0;D2;+0:6]=[O;D1;H0:7].[OH;D1;+0:8]-[C:9]-[c:10]>>[O;D1;H0:1]=[#16:2](=[O;D1;H0:3])(-[c:4])-[NH;D2;+0:5]-[C;H0;D3;+0:6](=[O;D1;H0:7])-[O;H0;D2;+0:8]-[C:9]-[c:10]
null
[]
55
CELSIUS
null
null
To a solution of 2-(4-chloro-2-hydroxymethyl-phenoxy)-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone (0.050 g, 0.12 mmol) in dry toluene (2 mL) was added triethylamine (0.05 mL, 0.36 mmol) followed by o-toluenesulfonylisocyanate (0.05 mL, 0.36 mmol) and catalytic 4-dimethylaminopyridine. After 23 ...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol
Sulfonamide.Carbamic ester
null
null
c1ccccc1.c1ccccc1.C1C[NH]CC[NH]1.c1ccccc1
null
CN(C1=CC=NC=C1)C.C1(=CC=CC=C1)C
55
null
C[C@@H]1CN(Cc2ccc(F)cc2)[C@@H](C)CN1C(=O)COc1ccc(Cl)cc1CO.Cc1ccccc1S(=O)(=O)N=C=O>CN(C1=CC=NC=C1)C.C1(=CC=CC=C1)C>Cc1ccccc1S(=O)(=O)NC(=O)OCc1cc(Cl)ccc1OCC(=O)N1C[C@H](C)N(Cc2ccc(F)cc2)C[C@H]1C
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
ord-cf5034813b064e95bf4b078c69cd9ad9
COC(=O)c1cc(Cl)ccc1OC>>COc1ccc(Cl)cc1CO
COC(C1=C(C=CC(=C1)Cl)OC)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>>ClC=1C=CC(=C(C1)CO)OC
CO[C:10]([c:9]1[c:3]([O:2][CH3:1])[cH:4][cH:5][c:6]([Cl:7])[cH:8]1)=[O:11]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([Cl:7])[cH:8][c:9]1[CH2:10][OH:11]
COC(=O)c1cc(Cl)ccc1OC
COc1ccc(Cl)cc1CO
null
null
C1CCOC1
Reduction
Reduction of ester to primary alcohol
21d61543c6ec8a8cebe1b3ef55ef3dd20acbf79a4f1c12a7fb51e32be7a3248a
1fbcd628a0426673c5d10aa49a977cd2d1ae02a8cdf57bbb10d94aa03a94e937
c1ccccc1
C-O-[C;H0;D3;+0:1](=[O;H0;D1;+0:2])-[c:3](:[c:4]):[c:5]>>[OH;D1;+0:2]-[CH2;D2;+0:1]-[c:3](:[c:4]):[c:5]
999.5
[{"value": 999.5, "product": "ClC=1C=CC(=C(C1)CO)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
null
null
To a solution of 5-chloro-2-methoxy-benzoic acid methyl ester (20 g, 9.97 mmol) in THF (100 mL) at 0° C. was added dropwise a solution of lithium aluminum hydride (210 mL, 210 mmol, 1M soln. in THF). The solution was then warmed to reflux for 2 hours. The reaction was cooled to 0° C. and carefully quenched by the addit...
10.6084/m9.figshare.5104873.v1
null
Ester
Primary alcohol
null
null
c1ccccc1
Other
C1CCOC1
0
null
COC(=O)c1cc(Cl)ccc1OC>C1CCOC1>COc1ccc(Cl)cc1CO