dataset_id
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-c31cb9b44c404c10ba3aa533aa079e2b
ord-f03ed9c7507f4091b2c9ef9cde7be8c9
COc1ccc(-c2ncn(CCC(C)(C)NCC(O)c3ccc(OCc4ccccc4)c(CO)c3)n2)cc1>>COc1ccc(-c2ncn(CCC(C)(C)NCC(O)c3ccc(O)c(CO)c3)n2)cc1
C(C1=CC=CC=C1)OC1=C(C=C(C=C1)C(CNC(CCN1N=C(N=C1)C1=CC=C(C=C1)OC)(C)C)O)CO>>OC(CNC(CCN1N=C(N=C1)C1=CC=C(C=C1)OC)(C)C)C1=CC(=C(C=C1)O)CO
c1ccc(C[O:24][c:23]2[cH:22][cH:21][c:20]([CH:18]([CH2:17][NH:16][C:13]([CH2:12][CH2:11][n:10]3[cH:9][n:8][c:7](-[c:6]4[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:31][cH:30]4)[n:29]3)([CH3:14])[CH3:15])[OH:19])[cH:28][c:25]2[CH2:26][OH:27])cc1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6](-[c:7]2[n:8][cH:9][n:10]([CH2:11][CH2:12][C:13]([...
COc1ccc(-c2ncn(CCC(C)(C)NCC(O)c3ccc(OCc4ccccc4)c(CO)c3)n2)cc1
COc1ccc(-c2ncn(CCC(C)(C)NCC(O)c3ccc(O)c(CO)c3)n2)cc1
null
[Pd]
O1CCCC1.CO
Deprotection
Hydroxyl benzyl deprotection
36869d1fe85185a14d9eb30bf05178c600a9b6eca277ffaf3803578c30e0bf5d
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc(CCNCCCn2cnc(-c3ccccc3)n2)cc1
[c:1]:[c:2](-[O;H0;D2;+0:3]-C-c1:c:c:c:c:c:1):[c:4]>>[OH;D1;+0:3]-[c:2](:[c:1]):[c:4]
null
[]
null
null
null
null
3.8 g of 1-(4-benzyloxy-3-hydroxymethyl-phenyl)-2-{3-[3-(4-methoxy-phenyl)-[1,2,4]triazol-1-yl]-1,1-dimethyl-propylamino}-ethanol are hydrogenated with 0.6 g of palladium on charcoal (5%) as catalyst in 75 mL methanol and 75 mL tetrahydrofuran. Then the catalyst is suction filtered and the filtrate is evaporated down. ...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
c1ccccc1
null
c1ccccc1.c1nnc[nH]1.c1ccccc1
Other
[Pd].O1CCCC1.CO
null
null
COc1ccc(-c2ncn(CCC(C)(C)NCC(O)c3ccc(OCc4ccccc4)c(CO)c3)n2)cc1>[Pd].O1CCCC1.CO>COc1ccc(-c2ncn(CCC(C)(C)NCC(O)c3ccc(O)c(CO)c3)n2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e9eb6ee0f02c4baba66eefb6b40f809a
CC(C)(N)CCn1cncn1.CCOC(O)C(=O)c1ccc(OCc2ccccc2)c(C(=O)OC)c1>>COC(=O)c1cc(C(O)CNC(C)(C)CCn2cncn2)ccc1OCc1ccccc1
C(C(=O)O)(=O)O.C(C1=CC=CC=C1)OC1=C(C(=O)OC)C=C(C=C1)C(C(O)OCC)=O.CC(CCN1N=CN=C1)(C)N>>C(C1=CC=CC=C1)OC1=C(C(=O)OC)C=C(C=C1)C(CNC(CCN1N=CN=C1)(C)C)O
[NH2:11][C:12]([CH3:13])([CH3:14])[CH2:15][CH2:16][n:17]1[cH:18][n:19][cH:20][n:21]1.CCO[CH:10](O)[C:8]([c:7]1[cH:6][c:5]([C:3]([O:2][CH3:1])=[O:4])[c:24]([O:25][CH2:26][c:27]2[cH:28][cH:29][cH:30][cH:31][cH:32]2)[cH:23][cH:22]1)=[O:9]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][c:7]([CH:8]([OH:9])[CH2:10][NH:11][C:12]([CH3...
CC(C)(N)CCn1cncn1.CCOC(O)C(=O)c1ccc(OCc2ccccc2)c(C(=O)OC)c1
COC(=O)c1cc(C(O)CNC(C)(C)CCn2cncn2)ccc1OCc1ccccc1
null
null
C(C)O
Heteroatom Alkylation and Arylation
OtherReaction
1fdebd18d8e186352a5054d1639a246066c291a759c2941bdb27defc05ab0b96
270f718637e505454980bf4a24a04f3a3a166f4d4160855797b4e1923ac25b66
c1ccc(COc2ccc(CCNCCCn3cncn3)cc2)cc1
C-C-O-[CH;D3;+0:1](-O)-[C;H0;D3;+0:2](=[O;H0;D1;+0:3])-[c:4](:[c:5]):[c:6].[C:7]-[C:8](-[C;D1;H3:9])(-[C;D1;H3:10])-[NH2;D1;+0:11]>>[C:7]-[C:8](-[C;D1;H3:9])(-[C;D1;H3:10])-[NH;D2;+0:11]-[CH2;D2;+0:1]-[CH;D3;+0:2](-[OH;D1;+0:3])-[c:4](:[c:5]):[c:6]
null
[]
null
null
null
null
9.5 g of methyl 2-benzyloxy-5-(2-ethoxy-2-hydroxy-acetyl)-benzoate and 3.1 g of 1,1-dimethyl-3-[1,2,4]triazol-1-yl-propylamine are reacted and worked up analogously to the method described for Example 2a. The crude product is dissolved in 100 mL 95% ethanol and combined with an ethanolic solution of 1.8 g of oxalic aci...
10.6084/m9.figshare.5104873.v1
null
Ketone.Ether.Secondary alcohol.Primary amine
Secondary alcohol.Secondary amine
null
null
c1ccccc1.c1nc[nH]n1.c1ccccc1
HO-
C(C)O
null
null
CC(C)(N)CCn1cncn1.CCOC(O)C(=O)c1ccc(OCc2ccccc2)c(C(=O)OC)c1>C(C)O>COC(=O)c1cc(C(O)CNC(C)(C)CCn2cncn2)ccc1OCc1ccccc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-6a530b77776841f8a59965f50e2d8619
COC(=O)c1cc(C(O)CNC(C)(C)CCn2cncn2)ccc1OCc1ccccc1>>CC(C)(CCn1cncn1)NCC(O)c1ccc(OCc2ccccc2)c(CO)c1
C(C1=CC=CC=C1)OC1=C(C(=O)OC)C=C(C=C1)C(CNC(CCN1N=CN=C1)(C)C)O.[Cl-].[Ca+2].[Cl-].[BH4-].[Na+]>>C(C1=CC=CC=C1)OC1=C(C=C(C=C1)C(CNC(CCN1N=CN=C1)(C)C)O)CO
CO[C:28]([c:27]1[c:18]([O:19][CH2:20][c:21]2[cH:22][cH:23][cH:24][cH:25][cH:26]2)[cH:17][cH:16][c:15]([CH:13]([CH2:12][NH:11][C:2]([CH3:1])([CH3:3])[CH2:4][CH2:5][n:6]2[cH:7][n:8][cH:9][n:10]2)[OH:14])[cH:30]1)=[O:29]>>[CH3:1][C:2]([CH3:3])([CH2:4][CH2:5][n:6]1[cH:7][n:8][cH:9][n:10]1)[NH:11][CH2:12][CH:13]([OH:14])[c:...
COC(=O)c1cc(C(O)CNC(C)(C)CCn2cncn2)ccc1OCc1ccccc1
CC(C)(CCn1cncn1)NCC(O)c1ccc(OCc2ccccc2)c(CO)c1
null
null
null
Reduction
Reduction of ester to primary alcohol
21d61543c6ec8a8cebe1b3ef55ef3dd20acbf79a4f1c12a7fb51e32be7a3248a
1fbcd628a0426673c5d10aa49a977cd2d1ae02a8cdf57bbb10d94aa03a94e937
c1ccc(COc2ccc(CCNCCCn3cncn3)cc2)cc1
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]
null
[]
null
null
null
null
7.6 g of methyl 2-benzyloxy-5-[2-[1,1-dimethyl-3-[1,2,4]triazol-1-yl-propylamino]-1-hydroxy-ethyl]-benzoate are reduced in an ethanolic calcium chloride solution with sodium borohydride as described for Example 1c. The product is obtained as a colourless oil after purification by column chromatography (CHCl3/MeOH/NH3=9...
10.6084/m9.figshare.5104873.v1
null
Ester
Primary alcohol
null
null
c1nc[nH]n1.c1ccccc1.c1ccccc1
Other
null
null
null
COC(=O)c1cc(C(O)CNC(C)(C)CCn2cncn2)ccc1OCc1ccccc1>>CC(C)(CCn1cncn1)NCC(O)c1ccc(OCc2ccccc2)c(CO)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f373ea10a6a84604b61c0f16d566114d
CC(C)(CCn1cncn1)NCC(O)c1ccc(OCc2ccccc2)c(CO)c1>>CC(C)(CCn1cncn1)NCC(O)c1ccc(O)c(CO)c1
C(C1=CC=CC=C1)OC1=C(C=C(C=C1)C(CNC(CCN1N=CN=C1)(C)C)O)CO>>CC(CCN1N=CN=C1)(C)NCC(O)C1=CC(=C(C=C1)O)CO
c1ccc(C[O:19][c:18]2[cH:17][cH:16][c:15]([CH:13]([CH2:12][NH:11][C:2]([CH3:1])([CH3:3])[CH2:4][CH2:5][n:6]3[cH:7][n:8][cH:9][n:10]3)[OH:14])[cH:23][c:20]2[CH2:21][OH:22])cc1>>[CH3:1][C:2]([CH3:3])([CH2:4][CH2:5][n:6]1[cH:7][n:8][cH:9][n:10]1)[NH:11][CH2:12][CH:13]([OH:14])[c:15]1[cH:16][cH:17][c:18]([OH:19])[c:20]([CH2...
CC(C)(CCn1cncn1)NCC(O)c1ccc(OCc2ccccc2)c(CO)c1
CC(C)(CCn1cncn1)NCC(O)c1ccc(O)c(CO)c1
null
[Pd]
CO
Deprotection
Hydroxyl benzyl deprotection
36869d1fe85185a14d9eb30bf05178c600a9b6eca277ffaf3803578c30e0bf5d
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc(CCNCCCn2cncn2)cc1
[c:1]:[c:2](-[O;H0;D2;+0:3]-C-c1:c:c:c:c:c:1):[c:4]>>[OH;D1;+0:3]-[c:2](:[c:1]):[c:4]
null
[]
null
null
null
null
The debenzylation of 6 g of 1-(4-benzyloxy-3-hydroxymethyl-phenyl)-2-(1,1-dimethyl-3-[1,2,4]triazol-1-yl-propylamino)-ethanol is carried out hydrogenolytically with 1 g of palladium on charcoal (5%) in 100 mL methanol. After the catalyst has been removed by suction filtering and the filtrate has been evaporated down th...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
c1ccccc1
null
c1nc[nH]n1.c1ccccc1
Other
[Pd].CO
null
null
CC(C)(CCn1cncn1)NCC(O)c1ccc(OCc2ccccc2)c(CO)c1>[Pd].CO>CC(C)(CCn1cncn1)NCC(O)c1ccc(O)c(CO)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d01719cb473e41ad981816ef2ffe3e85
CCOC(C)=N.Cc1ccc(C(=O)NN)cc1>>CC(=N)N(N)C(=O)c1ccc(C)cc1
[Na].Cl.C(C)OC(C)=N.CC1=CC=C(C(=O)NN)C=C1>>N=C(C)N(N)C(C1=CC=C(C=C1)C)=O
CCO[C:2]([CH3:1])=[NH:3].[NH:4]([NH2:5])[C:6](=[O:7])[c:8]1[cH:9][cH:10][c:11]([CH3:12])[cH:13][cH:14]1>>[CH3:1][C:2](=[NH:3])[N:4]([NH2:5])[C:6](=[O:7])[c:8]1[cH:9][cH:10][c:11]([CH3:12])[cH:13][cH:14]1
CCOC(C)=N.Cc1ccc(C(=O)NN)cc1
CC(=N)N(N)C(=O)c1ccc(C)cc1
null
null
C(C)O
Heteroatom Alkylation and Arylation
OtherReaction
fe324327bc33cfeacb108bab3ce14a06c4d02f9539f3b00ba33ac2a2ce6b4dcb
261d643341ab1545270a23dc6e2baca2b5f0751e834201694e9fa9a615f13907
c1ccccc1
C-C-O-[C;H0;D3;+0:1](-[C;D1;H3:2])=[N;D1;H1:3].[N;D1;H2:4]-[NH;D2;+0:5]-[C:6](=[O;D1;H0:7])-[c:8]>>[C;D1;H3:2]-[C;H0;D3;+0:1](=[N;D1;H1:3])-[N;H0;D3;+0:5](-[N;D1;H2:4])-[C:6](=[O;D1;H0:7])-[c:8]
15.7
[{"value": 15.7, "product": "N=C(C)N(N)C(C1=CC=C(C=C1)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
1.65 g (72 mmol) of sodium are dissolved in 80 mL ethanol. 8.89 g (72 mmol) of ethylacetimidate hydrochloride in 160 mL ethanol are added at ambient temperature and the precipitated sodium chloride is filtered off. The filtrate is combined with 6.00 g (40 mmol) 4-methyl-benzoic acid hydrazide and stirred overnight. The...
10.6084/m9.figshare.5104873.v1
null
Acylhydrazine.Ether
Acylhydrazine
null
null
c1ccccc1
HO-
C(C)O
null
8
CCOC(C)=N.Cc1ccc(C(=O)NN)cc1>C(C)O>CC(=N)N(N)C(=O)c1ccc(C)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a9735160f2dc458d91fffa7416777b23
CC(C)(CCCl)NC(=O)OC(C)(C)C.Cc1ccc(-c2n[nH]c(C)n2)cc1>>Cc1ccc(-c2nc(C)n(CCC(C)(C)NC(=O)OC(C)(C)C)n2)cc1
O.[H-].[Na+].CC1=NC(=NN1)C1=CC=C(C=C1)C.ClCCC(C)(C)NC(OC(C)(C)C)=O>>CC(CCN1N=C(N=C1C)C1=CC=C(C=C1)C)(C)NC(OC(C)(C)C)=O
Cl[CH2:11][CH2:12][C:13]([CH3:14])([CH3:15])[NH:16][C:17](=[O:18])[O:19][C:20]([CH3:21])([CH3:22])[CH3:23].[CH3:1][c:2]1[cH:3][cH:4][c:5](-[c:6]2[n:7][c:8]([CH3:9])[nH:10][n:24]2)[cH:25][cH:26]1>>[CH3:1][c:2]1[cH:3][cH:4][c:5](-[c:6]2[n:7][c:8]([CH3:9])[n:10]([CH2:11][CH2:12][C:13]([CH3:14])([CH3:15])[NH:16][C:17](=[O:...
CC(C)(CCCl)NC(=O)OC(C)(C)C.Cc1ccc(-c2n[nH]c(C)n2)cc1
Cc1ccc(-c2nc(C)n(CCC(C)(C)NC(=O)OC(C)(C)C)n2)cc1
null
[I-].C(CCC)[N+](CCCC)(CCCC)CCCC
C(C)(=O)OCC.CN1CCCN(C1=O)C
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
8bef00eaa42d3c717b13b9e6e5eb0aaa548aa02b0e5b8a7323f70bc5d1c7c865
2e1e5fd9557b69cb528f6b2ffd179c67ef24ecb1a2c3994e1cdf0efe7ae19e9c
c1ccc(-c2nc[nH]n2)cc1
Cl-[CH2;D2;+0:1]-[C:2]-[C:3].[C;D1;H3:4]-[c:5]1:[#7;a:6]:[c:7](-[c:8]):[#7;a:9]:[nH;D2;+0:10]:1>>[C:3]-[C:2]-[CH2;D2;+0:1]-[n;H0;D3;+0:10]1:[#7;a:9]:[c:7](-[c:8]):[#7;a:6]:[c:5]:1-[C;D1;H3:4]
null
[]
null
null
1
HOUR
1.35 g (34 mmol, 60%) sodium hydride are added to a solution of 4.87 g (28 mmol) of 5-methyl-3-p-tolyl-[1,2,4]triazole in 40 mL DMPU at 0° C. The reaction mixture is heated to ambient temperature and then stirred for one hour. 9.35 g (42 mmol) of tert.butyl (3-chloro-1,1-dimethyl-propyl)-carbamate and 1.87 g (5 mmol) o...
10.6084/m9.figshare.5104873.v1
null
Primary halide
null
c1nnc[nH]1
c1nnc[nH]1
c1ccccc1.c1nnc[nH]1
HCl
[I-].C(CCC)[N+](CCCC)(CCCC)CCCC.C(C)(=O)OCC.CN1CCCN(C1=O)C
null
1
CC(C)(CCCl)NC(=O)OC(C)(C)C.Cc1ccc(-c2n[nH]c(C)n2)cc1>[I-].C(CCC)[N+](CCCC)(CCCC)CCCC.C(C)(=O)OCC.CN1CCCN(C1=O)C>Cc1ccc(-c2nc(C)n(CCC(C)(C)NC(=O)OC(C)(C)C)n2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b09313c7b74d4df39d251089e8546b43
Cc1ccc(-c2nc(C)n(CCC(C)(C)NC(=O)OC(C)(C)C)n2)cc1>>Cc1ccc(-c2nc(C)n(CCC(C)(C)N)n2)cc1
FC(C(=O)O)(F)F.CC(CCN1N=C(N=C1C)C1=CC=C(C=C1)C)(C)NC(OC(C)(C)C)=O>>CC(CCN1N=C(N=C1C)C1=CC=C(C=C1)C)(C)N
CC(C)(C)OC(=O)[NH:16][C:13]([CH2:12][CH2:11][n:10]1[c:8]([CH3:9])[n:7][c:6](-[c:5]2[cH:4][cH:3][c:2]([CH3:1])[cH:19][cH:18]2)[n:17]1)([CH3:14])[CH3:15]>>[CH3:1][c:2]1[cH:3][cH:4][c:5](-[c:6]2[n:7][c:8]([CH3:9])[n:10]([CH2:11][CH2:12][C:13]([CH3:14])([CH3:15])[NH2:16])[n:17]2)[cH:18][cH:19]1
Cc1ccc(-c2nc(C)n(CCC(C)(C)NC(=O)OC(C)(C)C)n2)cc1
Cc1ccc(-c2nc(C)n(CCC(C)(C)N)n2)cc1
null
null
ClCCl
Reduction
Hydrogenolysis of amides/imides/carbamates
3c33dd2a2d355ee5ba0287367e209aa147a39aa00607f0c95fb2bf1ade45d014
c5b5dffe7dd8beebdc1baa8b5b05300a9f7079e65dcfd42ade6f8a77ff09537d
c1ccc(-c2nc[nH]n2)cc1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2](-[C:3])(-[C;D1;H3:4])-[C;D1;H3:5]>>[C:3]-[C:2](-[C;D1;H3:4])(-[C;D1;H3:5])-[NH2;D1;+0:1]
null
[]
null
null
8
HOUR
A total of 11 mL trifluoroacetic acid are added dropwise to a solution of 2.97 g (8.3 mmol) of tert.butyl [1,1-dimethyl-3-(5-methyl-3-p-tolyl-[1,2,4]triazol-1-yl)-propyl]-carbamate in 80 mL dichloromethane and the mixture is stirred overnight at ambient temperature. The solvent is distilled off and the residue is combi...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Primary amine
null
null
c1ccccc1.c1nnc[nH]1
HO-
ClCCl
null
8
Cc1ccc(-c2nc(C)n(CCC(C)(C)NC(=O)OC(C)(C)C)n2)cc1>ClCCl>Cc1ccc(-c2nc(C)n(CCC(C)(C)N)n2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b2cc11185257469d8d38bfba1120cb56
CC(C)(CCCl)NC(=O)OC(C)(C)C.Cc1nc(-c2ccc(F)cc2)n[nH]1>>Cc1nc(-c2ccc(F)cc2)nn1CCC(C)(C)NC(=O)OC(C)(C)C
ClCCC(C)(C)NC(OC(C)(C)C)=O.[H-].[Na+].FC1=CC=C(C=C1)C1=NNC(=N1)C>>FC1=CC=C(C=C1)C1=NN(C(=N1)C)CCC(C)(C)NC(OC(C)(C)C)=O
Cl[CH2:14][CH2:15][C:16]([CH3:17])([CH3:18])[NH:19][C:20](=[O:21])[O:22][C:23]([CH3:24])([CH3:25])[CH3:26].[CH3:1][c:2]1[n:3][c:4](-[c:5]2[cH:6][cH:7][c:8]([F:9])[cH:10][cH:11]2)[n:12][nH:13]1>>[CH3:1][c:2]1[n:3][c:4](-[c:5]2[cH:6][cH:7][c:8]([F:9])[cH:10][cH:11]2)[n:12][n:13]1[CH2:14][CH2:15][C:16]([CH3:17])([CH3:18])...
CC(C)(CCCl)NC(=O)OC(C)(C)C.Cc1nc(-c2ccc(F)cc2)n[nH]1
Cc1nc(-c2ccc(F)cc2)nn1CCC(C)(C)NC(=O)OC(C)(C)C
null
[I-].C(CCC)[N+](CCCC)(CCCC)CCCC
CN1CCCN(C1=O)C
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
8bef00eaa42d3c717b13b9e6e5eb0aaa548aa02b0e5b8a7323f70bc5d1c7c865
2e1e5fd9557b69cb528f6b2ffd179c67ef24ecb1a2c3994e1cdf0efe7ae19e9c
c1ccc(-c2nc[nH]n2)cc1
Cl-[CH2;D2;+0:1]-[C:2]-[C:3].[C;D1;H3:4]-[c:5]1:[#7;a:6]:[c:7](-[c:8]):[#7;a:9]:[nH;D2;+0:10]:1>>[C:3]-[C:2]-[CH2;D2;+0:1]-[n;H0;D3;+0:10]1:[#7;a:9]:[c:7](-[c:8]):[#7;a:6]:[c:5]:1-[C;D1;H3:4]
null
[]
null
null
null
null
5.88 g (33 mmol) of 3-(4-fluoro-phenyl)-5-methyl-[1,2,4]triazole are dissolved in 40 mL DMPU and reacted with 11.04 g (50 mmol) of tert.butyl (3-chloro-1,1-dimethyl-propyl)-carbamate, 1.59 g (40 mmol, 60%) of sodium hydride and 2.21 g (6 mmol) of tetrabutylammonium iodide in the manner described in P-1-c). Conditions: ...
10.6084/m9.figshare.5104873.v1
null
Primary halide
null
c1nnc[nH]1
c1nnc[nH]1
c1nnc[nH]1.c1ccccc1
HCl
[I-].C(CCC)[N+](CCCC)(CCCC)CCCC.CN1CCCN(C1=O)C
null
null
CC(C)(CCCl)NC(=O)OC(C)(C)C.Cc1nc(-c2ccc(F)cc2)n[nH]1>[I-].C(CCC)[N+](CCCC)(CCCC)CCCC.CN1CCCN(C1=O)C>Cc1nc(-c2ccc(F)cc2)nn1CCC(C)(C)NC(=O)OC(C)(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-be8785509a74442a8b9d8d877d506d40
CC(C)(CCCl)NC(=O)OC(C)(C)C.Cc1nc(-c2cc(F)cc(F)c2)n[nH]1>>Cc1nc(-c2cc(F)cc(F)c2)nn1CCC(C)(C)NC(=O)OC(C)(C)C
FC=1C=C(C=C(C1)F)C1=NNC(=N1)C.[H-].[Na+].ClCCC(C)(C)NC(OC(C)(C)C)=O>>FC=1C=C(C=C(C1)F)C1=NN(C(=N1)C)CCC(C)(C)NC(OC(C)(C)C)=O
Cl[CH2:15][CH2:16][C:17]([CH3:18])([CH3:19])[NH:20][C:21](=[O:22])[O:23][C:24]([CH3:25])([CH3:26])[CH3:27].[CH3:1][c:2]1[n:3][c:4](-[c:5]2[cH:6][c:7]([F:8])[cH:9][c:10]([F:11])[cH:12]2)[n:13][nH:14]1>>[CH3:1][c:2]1[n:3][c:4](-[c:5]2[cH:6][c:7]([F:8])[cH:9][c:10]([F:11])[cH:12]2)[n:13][n:14]1[CH2:15][CH2:16][C:17]([CH3:...
CC(C)(CCCl)NC(=O)OC(C)(C)C.Cc1nc(-c2cc(F)cc(F)c2)n[nH]1
Cc1nc(-c2cc(F)cc(F)c2)nn1CCC(C)(C)NC(=O)OC(C)(C)C
null
[I-].C(CCC)[N+](CCCC)(CCCC)CCCC
CN1CCCN(C1=O)C
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
8bef00eaa42d3c717b13b9e6e5eb0aaa548aa02b0e5b8a7323f70bc5d1c7c865
2e1e5fd9557b69cb528f6b2ffd179c67ef24ecb1a2c3994e1cdf0efe7ae19e9c
c1ccc(-c2nc[nH]n2)cc1
Cl-[CH2;D2;+0:1]-[C:2]-[C:3].[C;D1;H3:4]-[c:5]1:[#7;a:6]:[c:7](-[c:8]):[#7;a:9]:[nH;D2;+0:10]:1>>[C:3]-[C:2]-[CH2;D2;+0:1]-[n;H0;D3;+0:10]1:[#7;a:9]:[c:7](-[c:8]):[#7;a:6]:[c:5]:1-[C;D1;H3:4]
null
[]
null
null
null
null
3.74 g (19 mmol) of 3-(3,5-difluoro-phenyl)-5-methyl-[1,2,4]triazole in 25 mL DMPU are reacted with 0.92 g (23 mmol, 60%) of sodium hydride, 6.37 g (29 mmol) of tert.butyl (3-chloro-1,1-dimethyl-propyl)-carbamate and 1.27 g (3.5 mmol) of tetrabutylammonium iodide analogously to P-1-c). Oil. Conditions: See reaction.not...
10.6084/m9.figshare.5104873.v1
null
Primary halide
null
c1nnc[nH]1
c1nnc[nH]1
c1nnc[nH]1.c1ccccc1
HCl
[I-].C(CCC)[N+](CCCC)(CCCC)CCCC.CN1CCCN(C1=O)C
null
null
CC(C)(CCCl)NC(=O)OC(C)(C)C.Cc1nc(-c2cc(F)cc(F)c2)n[nH]1>[I-].C(CCC)[N+](CCCC)(CCCC)CCCC.CN1CCCN(C1=O)C>Cc1nc(-c2cc(F)cc(F)c2)nn1CCC(C)(C)NC(=O)OC(C)(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-00c1178714e54103bd2c468d0d4bb1bd
CCC(=N)N.COc1ccc(C(=O)NN)cc1>>CCC(=N)N(N)C(=O)c1ccc(OC)cc1
Cl.C(CC)(=N)N.COC1=CC=C(C(=O)NN)C=C1>>N=C(CC)N(N)C(C1=CC=C(C=C1)OC)=O
N[C:3]([CH2:2][CH3:1])=[NH:4].[NH:5]([NH2:6])[C:7](=[O:8])[c:9]1[cH:10][cH:11][c:12]([O:13][CH3:14])[cH:15][cH:16]1>>[CH3:1][CH2:2][C:3](=[NH:4])[N:5]([NH2:6])[C:7](=[O:8])[c:9]1[cH:10][cH:11][c:12]([O:13][CH3:14])[cH:15][cH:16]1
CCC(=N)N.COc1ccc(C(=O)NN)cc1
CCC(=N)N(N)C(=O)c1ccc(OC)cc1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
881186226d68555da074f393b7f41ec9b9a8312187844874bad4ad0ff35d9a64
29975e1d65e16090ba2ff7b9d7c27d2b9cd4263bd4cf95c313c0d29e9a47bc8f
c1ccccc1
N-[C;H0;D3;+0:1](=[N;D1;H1:2])-[C:3]-[C;D1;H3:4].[N;D1;H2:5]-[NH;D2;+0:6]-[C:7](=[O;D1;H0:8])-[c:9]>>[C;D1;H3:4]-[C:3]-[C;H0;D3;+0:1](=[N;D1;H1:2])-[N;H0;D3;+0:6](-[N;D1;H2:5])-[C:7](=[O;D1;H0:8])-[c:9]
null
[]
null
null
null
null
Prepared from 4.90 g (45 mmol) of propioamidine hydrochloride and 5.00 g (30 mmol) of 4-methoxy-benzoic acid hydrazide analogously to the method described in P-1-a). After the ethanol has been distilled off 10.0 g of crude product are obtained which are reacted without any further purification. Conditions: See reaction...
10.6084/m9.figshare.5104873.v1
null
Acylhydrazine.Primary amine
Acylhydrazine
null
null
c1ccccc1
Other
null
null
null
CCC(=N)N.COc1ccc(C(=O)NN)cc1>>CCC(=N)N(N)C(=O)c1ccc(OC)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5e6f2fd3a3bf42e88505fcf3d36a1220
CCOC(O)C(=O)c1ccc(OCc2ccccc2)c(C(=O)OC)c1.Cc1ccc(-c2nc(C)n(CCC(C)(C)N)n2)cc1>>Cc1ccc(-c2nc(C)n(CCC(C)(C)NCC(O)c3ccc(O)c(CO)c3)n2)cc1
C(C1=CC=CC=C1)OC1=C(C(=O)OC)C=C(C=C1)C(C(O)OCC)=O.CC(CCN1N=C(N=C1C)C1=CC=C(C=C1)C)(C)N>>CC(CCN1N=C(N=C1C)C1=CC=C(C=C1)C)(C)NCC(O)C1=CC(=C(C=C1)O)CO
CCO[CH:17](O)[C:18](=[O:19])[c:20]1[cH:21][cH:22][c:23]([O:24]Cc2ccccc2)[c:25]([C:26](OC)=[O:27])[cH:28]1.[CH3:1][c:2]1[cH:3][cH:4][c:5](-[c:6]2[n:7][c:8]([CH3:9])[n:10]([CH2:11][CH2:12][C:13]([CH3:14])([CH3:15])[NH2:16])[n:29]2)[cH:30][cH:31]1>>[CH3:1][c:2]1[cH:3][cH:4][c:5](-[c:6]2[n:7][c:8]([CH3:9])[n:10]([CH2:11][C...
CCOC(O)C(=O)c1ccc(OCc2ccccc2)c(C(=O)OC)c1.Cc1ccc(-c2nc(C)n(CCC(C)(C)N)n2)cc1
Cc1ccc(-c2nc(C)n(CCC(C)(C)NCC(O)c3ccc(O)c(CO)c3)n2)cc1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
34f8f4a6788d6c681d3e1d1d0ca8cdb0b22b34660b85a60626fbfbee66b0a978
4448e1ae18d5453e19796a86532c96366da07d8e645a2eff499c2e2676c0517a
c1ccc(CCNCCCn2cnc(-c3ccccc3)n2)cc1
C-C-O-[CH;D3;+0:1](-O)-[C;H0;D3;+0:2](=[O;H0;D1;+0:3])-[c:4]1:[c:5]:[c:6]:[c:7](-[O;H0;D2;+0:8]-C-c2:c:c:c:c:c:2):[c:9](-[C;H0;D3;+0:10](=[O;H0;D1;+0:11])-O-C):[c:12]:1.[C:13]-[C:14](-[C;D1;H3:15])(-[C;D1;H3:16])-[NH2;D1;+0:17]>>[C:13]-[C:14](-[C;D1;H3:15])(-[C;D1;H3:16])-[NH;D2;+0:17]-[CH2;D2;+0:1]-[CH;D3;+0:2](-[OH;D...
null
[]
null
null
null
null
The compound is prepared analogously to the general working method A from 241 mg (0.7 mmol) of methyl 2-benzyloxy-5-(2-ethoxy-2-hydroxy-acetyl)-benzoate and 181 mg (0.7 mmol) of 1,1-dimethyl-3-(5-methyl-3-p-tolyl-[1,2,4]triazol-1-yl)-propylamine. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Ketone.Ester.Ether.Ether.Secondary alcohol.Primary amine
Primary alcohol.Secondary alcohol.Aromatic alcohol.Secondary amine
c1ccccc1
null
c1ccccc1.c1nnc[nH]1.c1ccccc1
HO-
null
null
null
CCOC(O)C(=O)c1ccc(OCc2ccccc2)c(C(=O)OC)c1.Cc1ccc(-c2nc(C)n(CCC(C)(C)N)n2)cc1>>Cc1ccc(-c2nc(C)n(CCC(C)(C)NCC(O)c3ccc(O)c(CO)c3)n2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-06dc23e17530430893a7bcabb9eda233
CCOC(O)C(=O)c1ccc(OCc2ccccc2)c(C(=O)OC)c1.Cc1nc(-c2cc(F)cc(F)c2)nn1CCC(C)(C)N>>Cc1nc(-c2cc(F)cc(F)c2)nn1CCC(C)(C)NCC(O)c1ccc(O)c(CO)c1
C(C1=CC=CC=C1)OC1=C(C(=O)OC)C=C(C=C1)C(C(O)OCC)=O.FC=1C=C(C=C(C1)F)C1=NN(C(=N1)C)CCC(C)(C)N>>FC=1C=C(C=C(C1)F)C1=NN(C(=N1)C)CCC(C)(C)NCC(O)C1=CC(=C(C=C1)O)CO
CCO[CH:21](O)[C:22](=[O:23])[c:24]1[cH:25][cH:26][c:27]([O:28]Cc2ccccc2)[c:29]([C:30](OC)=[O:31])[cH:32]1.[CH3:1][c:2]1[n:3][c:4](-[c:5]2[cH:6][c:7]([F:8])[cH:9][c:10]([F:11])[cH:12]2)[n:13][n:14]1[CH2:15][CH2:16][C:17]([CH3:18])([CH3:19])[NH2:20]>>[CH3:1][c:2]1[n:3][c:4](-[c:5]2[cH:6][c:7]([F:8])[cH:9][c:10]([F:11])[c...
CCOC(O)C(=O)c1ccc(OCc2ccccc2)c(C(=O)OC)c1.Cc1nc(-c2cc(F)cc(F)c2)nn1CCC(C)(C)N
Cc1nc(-c2cc(F)cc(F)c2)nn1CCC(C)(C)NCC(O)c1ccc(O)c(CO)c1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
34f8f4a6788d6c681d3e1d1d0ca8cdb0b22b34660b85a60626fbfbee66b0a978
4448e1ae18d5453e19796a86532c96366da07d8e645a2eff499c2e2676c0517a
c1ccc(CCNCCCn2cnc(-c3ccccc3)n2)cc1
C-C-O-[CH;D3;+0:1](-O)-[C;H0;D3;+0:2](=[O;H0;D1;+0:3])-[c:4]1:[c:5]:[c:6]:[c:7](-[O;H0;D2;+0:8]-C-c2:c:c:c:c:c:2):[c:9](-[C;H0;D3;+0:10](=[O;H0;D1;+0:11])-O-C):[c:12]:1.[C:13]-[C:14](-[C;D1;H3:15])(-[C;D1;H3:16])-[NH2;D1;+0:17]>>[C:13]-[C:14](-[C;D1;H3:15])(-[C;D1;H3:16])-[NH;D2;+0:17]-[CH2;D2;+0:1]-[CH;D3;+0:2](-[OH;D...
null
[]
null
null
null
null
The compound is obtained according to general working method A from 121 mg (0.35 mmol) of methyl 2-benzyloxy-5-(2-ethoxy-2-hydroxy-acetyl)-benzoate and 98 mg (0.35 mmol) of 3-[3-(3,5-difluoro-phenyl)-5-methyl-[1,2,4]triazol-1-yl]-1,1-dimethyl-propylamine. Yield: 9 mg (6%); mass spectroscopy [M+H]+=447. Conditions: See ...
10.6084/m9.figshare.5104873.v1
null
Ketone.Ester.Ether.Ether.Secondary alcohol.Primary amine
Primary alcohol.Secondary alcohol.Aromatic alcohol.Secondary amine
c1ccccc1
null
c1nnc[nH]1.c1ccccc1.c1ccccc1
HO-
null
null
null
CCOC(O)C(=O)c1ccc(OCc2ccccc2)c(C(=O)OC)c1.Cc1nc(-c2cc(F)cc(F)c2)nn1CCC(C)(C)N>>Cc1nc(-c2cc(F)cc(F)c2)nn1CCC(C)(C)NCC(O)c1ccc(O)c(CO)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e5d952dab2484b08a7aa51cb7c6ebfd4
CCOC(O)C(=O)c1ccc(OCc2ccccc2)c(C(=O)OC)c1.Cc1nc(-c2ccc(F)cc2)nn1CCC(C)(C)N>>Cc1nc(-c2ccc(F)cc2)nn1CCC(C)(C)NCC(O)c1ccc(O)c(CO)c1
C(C1=CC=CC=C1)OC1=C(C(=O)OC)C=C(C=C1)C(C(O)OCC)=O.FC1=CC=C(C=C1)C1=NN(C(=N1)C)CCC(C)(C)N>>FC1=CC=C(C=C1)C1=NN(C(=N1)C)CCC(C)(C)NCC(O)C1=CC(=C(C=C1)O)CO
CCO[CH:20](O)[C:21](=[O:22])[c:23]1[cH:24][cH:25][c:26]([O:27]Cc2ccccc2)[c:28]([C:29](OC)=[O:30])[cH:31]1.[CH3:1][c:2]1[n:3][c:4](-[c:5]2[cH:6][cH:7][c:8]([F:9])[cH:10][cH:11]2)[n:12][n:13]1[CH2:14][CH2:15][C:16]([CH3:17])([CH3:18])[NH2:19]>>[CH3:1][c:2]1[n:3][c:4](-[c:5]2[cH:6][cH:7][c:8]([F:9])[cH:10][cH:11]2)[n:12][...
CCOC(O)C(=O)c1ccc(OCc2ccccc2)c(C(=O)OC)c1.Cc1nc(-c2ccc(F)cc2)nn1CCC(C)(C)N
Cc1nc(-c2ccc(F)cc2)nn1CCC(C)(C)NCC(O)c1ccc(O)c(CO)c1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
34f8f4a6788d6c681d3e1d1d0ca8cdb0b22b34660b85a60626fbfbee66b0a978
4448e1ae18d5453e19796a86532c96366da07d8e645a2eff499c2e2676c0517a
c1ccc(CCNCCCn2cnc(-c3ccccc3)n2)cc1
C-C-O-[CH;D3;+0:1](-O)-[C;H0;D3;+0:2](=[O;H0;D1;+0:3])-[c:4]1:[c:5]:[c:6]:[c:7](-[O;H0;D2;+0:8]-C-c2:c:c:c:c:c:2):[c:9](-[C;H0;D3;+0:10](=[O;H0;D1;+0:11])-O-C):[c:12]:1.[C:13]-[C:14](-[C;D1;H3:15])(-[C;D1;H3:16])-[NH2;D1;+0:17]>>[C:13]-[C:14](-[C;D1;H3:15])(-[C;D1;H3:16])-[NH;D2;+0:17]-[CH2;D2;+0:1]-[CH;D3;+0:2](-[OH;D...
null
[]
null
null
null
null
Prepared according to general working method A from 344 mg (1 mmol) of methyl 2-benzyloxy-5-(2-ethoxy-2-hydroxy-acetyl)-benzoate and 262 mg (1 mmol) of 3-[3-(4-fluoro-phenyl)-5-methyl-[1,2,4]triazol-1-yl]-1,1-dimethyl-propylamine. Conditions: See reaction.notes.procedure_details. Workup: Prepared
10.6084/m9.figshare.5104873.v1
null
Ketone.Ester.Ether.Ether.Secondary alcohol.Primary amine
Primary alcohol.Secondary alcohol.Aromatic alcohol.Secondary amine
c1ccccc1
null
c1nnc[nH]1.c1ccccc1.c1ccccc1
HO-
null
null
null
CCOC(O)C(=O)c1ccc(OCc2ccccc2)c(C(=O)OC)c1.Cc1nc(-c2ccc(F)cc2)nn1CCC(C)(C)N>>Cc1nc(-c2ccc(F)cc2)nn1CCC(C)(C)NCC(O)c1ccc(O)c(CO)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-0846c3af3db74fb580a9cab8a8c1a031
CC(O)CN.O=C(Cl)OCc1ccccc1>>CC(O)CNC(=O)OCc1ccccc1
NCC(C)O.ClC(=O)OCC1=CC=CC=C1.C([O-])([O-])=O.[Na+].[Na+]>>C(C1=CC=CC=C1)OC(=O)NCC(C)O
[CH3:1][CH:2]([OH:3])[CH2:4][NH2:5].Cl[C:6](=[O:7])[O:8][CH2:9][c:10]1[cH:11][cH:12][cH:13][cH:14][cH:15]1>>[CH3:1][CH:2]([OH:3])[CH2:4][NH:5][C:6](=[O:7])[O:8][CH2:9][c:10]1[cH:11][cH:12][cH:13][cH:14][cH:15]1
CC(O)CN.O=C(Cl)OCc1ccccc1
CC(O)CNC(=O)OCc1ccccc1
null
null
O
Protection
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
038720aa61a7efa0f2a9ee6f2e0adf63a9ffdc2be4697c11a6215baef34f97b2
205f353513ce9506ab61831799da8fb73ec2ef5cfa927664496d3ce72c438860
c1ccccc1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[C:4].[C:5]-[C:6]-[NH2;D1;+0:7]>>[C:5]-[C:6]-[NH;D2;+0:7]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[C:4]
100
[{"value": 100.0, "product": "C(C1=CC=CC=C1)OC(=O)NCC(C)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 99.8, "product": "C(C1=CC=CC=C1)OC(=O)NCC(C)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
3
HOUR
A mixture of 1-amino-2-propanol (1) (4.6 g, 61.8 mmol), benzyl chloroformate (11.5 g, 67.6 mmol), and sodium carbonate (7.16 g, 67.7 mmol) in water (50 mL) was stirred at 0° C. for 3 h. Water (50 mL) was added to the reaction mixture, the product was extracted with CH2Cl2 (3×20 mL), dried over Na2SO4 and concentrated. ...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Ether.Primary amine
Carbamic ester
null
null
c1ccccc1
HCl
O
0
3
CC(O)CN.O=C(Cl)OCc1ccccc1>O>CC(O)CNC(=O)OCc1ccccc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-94190286fc6e4421925b30e93ae48177
CC(O)CNC(=O)OCc1ccccc1>>CC(=O)CNC(=O)OCc1ccccc1
CCN(CC)CC.C(C1=CC=CC=C1)OC(=O)NCC(C)O.C(C(=O)Cl)(=O)Cl.CS(=O)C>>C(C1=CC=CC=C1)OC(=O)NCC(C)=O
[CH3:1][CH:2]([OH:3])[CH2:4][NH:5][C:6](=[O:7])[O:8][CH2:9][c:10]1[cH:11][cH:12][cH:13][cH:14][cH:15]1>>[CH3:1][C:2](=[O:3])[CH2:4][NH:5][C:6](=[O:7])[O:8][CH2:9][c:10]1[cH:11][cH:12][cH:13][cH:14][cH:15]1
CC(O)CNC(=O)OCc1ccccc1
CC(=O)CNC(=O)OCc1ccccc1
null
null
C(Cl)Cl
Oxidation
Oxidation or Dehydrogenation of Alcohols to Aldehydes and Ketones
c7c20d2959ac48847b03cc1265962cf99a8ec8a85900c087dabb30077298c66c
767cfd93f5821ebb9e1e72addd9cb404b20b0c821d246ae6b87a5776b74a455b
c1ccccc1
[C;D1;H3:1]-[CH;D3;+0:2](-[OH;D1;+0:3])-[C:4]-[#7:5]-[C:6]=[O;D1;H0:7]>>[C;D1;H3:1]-[C;H0;D3;+0:2](=[O;H0;D1;+0:3])-[C:4]-[#7:5]-[C:6]=[O;D1;H0:7]
81
[{"value": 81.0, "product": "C(C1=CC=CC=C1)OC(=O)NCC(C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 79.6, "product": "C(C1=CC=CC=C1)OC(=O)NCC(C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-78
CELSIUS
20
MINUTE
To a solution of oxalyl chloride (37 mL, 2 M solution in CH2Cl2, 74 mmol) in CH2Cl2 (60 mL) at −78° C. under argon was added DMSO (7.8 g, 100 mmol). The mixture was stirred at −78° C. for 20 min, and to this mixture was added a solution of 1-benzyloxycarbonylamino-2-propanol (2) (12.9 g, 61.8 mmol) in CH2Cl2 (40 mL). T...
10.6084/m9.figshare.5104873.v1
null
Secondary alcohol
Ketone
null
null
c1ccccc1
null
C(Cl)Cl
-78
0.333333
CC(O)CNC(=O)OCc1ccccc1>C(Cl)Cl>CC(=O)CNC(=O)OCc1ccccc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-67649b5714094ab7943abcf6ed07b1b7
CC(=O)CN.O=C(O)C(Cc1ccc(OCc2ccccc2)cc1)N1C(=O)c2ccccc2C1=O>>CC(=O)CNC(=O)C(Cc1ccc(OCc2ccccc2)cc1)N1C(=O)c2ccccc2C1=O
Cl.NCC(C)=O.C(C1=CC=CC=C1)OC1=CC=C(C=C1)CC(C(=O)O)N1C(C2=CC=CC=C2C1=O)=O.C=1C=CC2=C(C1)N=NN2O.CCN=C=NCCCN(C)C.CCN(CC)CC>>C(C1=CC=CC=C1)OC1=CC=C(C=C1)CC(C(=O)NCC(C)=O)N1C(C2=CC=CC=C2C1=O)=O
[CH3:1][C:2](=[O:3])[CH2:4][NH2:5].O[C:6](=[O:7])[CH:8]([CH2:9][c:10]1[cH:11][cH:12][c:13]([O:14][CH2:15][c:16]2[cH:17][cH:18][cH:19][cH:20][cH:21]2)[cH:22][cH:23]1)[N:24]1[C:25](=[O:26])[c:27]2[cH:28][cH:29][cH:30][cH:31][c:32]2[C:33]1=[O:34]>>[CH3:1][C:2](=[O:3])[CH2:4][NH:5][C:6](=[O:7])[CH:8]([CH2:9][c:10]1[cH:11][...
CC(=O)CN.O=C(O)C(Cc1ccc(OCc2ccccc2)cc1)N1C(=O)c2ccccc2C1=O
CC(=O)CNC(=O)C(Cc1ccc(OCc2ccccc2)cc1)N1C(=O)c2ccccc2C1=O
null
null
O.CN(C)C=O
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C1c2ccccc2C(=O)N1CCc1ccc(OCc2ccccc2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])-[#7:5](-[C:6]=[O;D1;H0:7])-[C:8]=[O;D1;H0:9].[C;D1;H3:10]-[C:11](=[O;D1;H0:12])-[C:13]-[NH2;D1;+0:14]>>[C:4]-[C:3](-[#7:5](-[C:6]=[O;D1;H0:7])-[C:8]=[O;D1;H0:9])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:14]-[C:13]-[C:11](-[C;D1;H3:10])=[O;D1;H0:12]
88
[{"value": 88.0, "product": "C(C1=CC=CC=C1)OC1=CC=C(C=C1)CC(C(=O)NCC(C)=O)N1C(C2=CC=CC=C2C1=O)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 87.6, "product": "C(C1=CC=CC=C1)OC1=CC=C(C=C1)CC(C(=O)NCC(C)=O)N1C(C2=CC=CC=C2C1=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
0.5
HOUR
A mixture of 3-(4-benzyloxy-phenyl)-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-propionic acid (500 mg, 1.25 mmol), HOBt (180 mg, 2.5 mmol), and EDCI (480 mg, 2.5 mmol) in DMF (3 mL) was stirred at 0° C. for 0.5 h. To this mixture was added 1-amino-2-propanone hydrochloride (4) (272 mg, 2.5 mmol) followed by Et3N (550 □L, ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccccc1.c1ccc2c(c1)C[NH]C2
HO-
O.CN(C)C=O
0
0.5
CC(=O)CN.O=C(O)C(Cc1ccc(OCc2ccccc2)cc1)N1C(=O)c2ccccc2C1=O>O.CN(C)C=O>CC(=O)CNC(=O)C(Cc1ccc(OCc2ccccc2)cc1)N1C(=O)c2ccccc2C1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d2f816afef8946e591b0b16b2214f1a5
CC(=O)CNC(=O)C(Cc1ccc(OCc2ccccc2)cc1)N1C(=O)c2ccccc2C1=O>>CC(=O)Oc1ccc(CC(c2ncc(C)o2)N2C(=O)c3ccccc3C2=O)cc1
C(C)(=O)[O-].[Na+].C(C1=CC=CC=C1)OC1=CC=C(C=C1)CC(C(=O)NCC(C)=O)N1C(C2=CC=CC=C2C1=O)=O.S(O)(O)(=O)=O>>O=C1N(C(C2=CC=CC=C12)=O)C(CC1=CC=C(C=C1)OC(C)=O)C=1OC(=CN1)C
O=[C:14]([CH2:13][NH:12][C:11]([CH:10]([CH2:9][c:8]1[cH:7][cH:6][c:5]([O:4]Cc2ccccc2)[cH:29][cH:28]1)[N:17]1[C:18](=[O:19])[c:20]2[cH:21][cH:22][cH:23][cH:24][c:25]2[C:26]1=[O:27])=[O:16])[CH3:15]>>[CH3:1][C:2](=[O:3])[O:4][c:5]1[cH:6][cH:7][c:8]([CH2:9][CH:10]([c:11]2[n:12][cH:13][c:14]([CH3:15])[o:16]2)[N:17]2[C:18](...
CC(=O)CNC(=O)C(Cc1ccc(OCc2ccccc2)cc1)N1C(=O)c2ccccc2C1=O
CC(=O)Oc1ccc(CC(c2ncc(C)o2)N2C(=O)c3ccccc3C2=O)cc1
null
null
C(C)(=O)OC(C)=O
Reduction
OtherReaction
c7bc602c79cc0d343fab98c3a176bdd6786ca2e12fbca669ada54bed1717a521
97e2ecf86f40b2e93e098f38aa85ca1db95baab3228abb0fdcc72152492d8f10
O=C1c2ccccc2C(=O)N1C(Cc1ccccc1)c1ncco1
O=[C;H0;D3;+0:1](-[C;D1;H3:2])-[CH2;D2;+0:3]-[NH;D2;+0:4]-[C;H0;D3;+0:5](=[O;H0;D1;+0:6])-[C:7](-[C:8])-[#7:9](-[C:10]=[O;D1;H0:11])-[C:12]=[O;D1;H0:13].[c:14]:[c:15](-[O;H0;D2;+0:16]-C-c1:c:c:c:c:c:1):[c:17]>>[C;D1;H3:18]-[C:19](=[O;D1;H0:20])-[O;H0;D2;+0:16]-[c:15](:[c:14]):[c:17].[C:8]-[C:7](-[#7:9](-[C:10]=[O;D1;H0...
56
[{"value": 56.0, "product": "O=C1N(C(C2=CC=CC=C12)=O)C(CC1=CC=C(C=C1)OC(C)=O)C=1OC(=CN1)C", "details": "PERCENTYIELD", "is_desired": false}]
57.5
CELSIUS
2
HOUR
To a solution of 3-(4-Benzyloxy-phenyl)-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-N-(2-oxo-propyl)-propionamide (5) (220 mg, 0.5 mmol) in acetic anhydride (2 mL) at room temperature was added concentrated sulfuric acid (0.2 mL). The mixture was stirred at 55-60° C. for 2 h, then sodium acetate (200 mg) was added, and the...
10.6084/m9.figshare.5104873.v1
null
Ketone.Ether.Secondary amide
Ester
c1ccccc1
c1cocn1
c1ccccc1.c1cocn1.c1ccc2c(c1)C[NH]C2
HO-
C(C)(=O)OC(C)=O
57.5
2
CC(=O)CNC(=O)C(Cc1ccc(OCc2ccccc2)cc1)N1C(=O)c2ccccc2C1=O>C(C)(=O)OC(C)=O>CC(=O)Oc1ccc(CC(c2ncc(C)o2)N2C(=O)c3ccccc3C2=O)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2b99da6e97b8436a8959456d82cfddc4
CC(O)CN.Cc1ccccc1.O=C1OC(=O)c2ccccc21>>CC(O)CNC(=O)OCc1ccccc1
NCC(C)O.C1(C=2C(C(=O)O1)=CC=CC2)=O.C(C)N(CC)CC.C1(=CC=CC=C1)C>>C(C1=CC=CC=C1)OC(=O)NCC(C)O
[CH3:1][CH:2]([OH:3])[CH2:4][NH2:5].[CH3:9][c:10]1[cH:11][cH:12][cH:13][cH:14][cH:15]1.O=C1c2ccccc2[C:6](=[O:7])[O:8]1>>[CH3:1][CH:2]([OH:3])[CH2:4][NH:5][C:6](=[O:7])[O:8][CH2:9][c:10]1[cH:11][cH:12][cH:13][cH:14][cH:15]1
CC(O)CN.Cc1ccccc1.O=C1OC(=O)c2ccccc21
CC(O)CNC(=O)OCc1ccccc1
null
null
O
Protection
OtherReaction
f7c969f78f0ccd827c55ebd06a1de19d35b3212f4ea0cbd9b6f08cc094d1e863
d9c1951fa6bdd53d2581c243a75e964e0e16f6982143c2014721802f893c561b
c1ccccc1
O=C1-[O;H0;D2;+0:1]-[C;H0;D3;+0:2](=[O;D1;H0:3])-c2:c:c:c:c:c:2-1.[CH3;D1;+0:4]-[c:5](:[c:6]):[c:7].[C:8]-[C:9]-[NH2;D1;+0:10]>>[C:8]-[C:9]-[NH;D2;+0:10]-[C;H0;D3;+0:2](=[O;D1;H0:3])-[O;H0;D2;+0:1]-[CH2;D2;+0:4]-[c:5](:[c:6]):[c:7]
142.1
[{"value": 142.1, "product": "C(C1=CC=CC=C1)OC(=O)NCC(C)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a round bottom flask equipped with Dean-Stark trap was added (1) (2 g, 7.4 mmol), phthalic anhydride (1.1 g, 7.4 mmol), triethylamine (0.1 mL) and toluene (50 mL). The reaction mixture was heated to reflux and water produced was collected. After refluxing for 2 hours, the solvent was removed. The residue was acidifi...
10.6084/m9.figshare.5104873.v1
null
Anhydride.Ester.Ester.Primary amine
Carbamic ester.Ether
c1ccc2c(c1)COC2
null
c1ccccc1
HO-
O
null
null
CC(O)CN.Cc1ccccc1.O=C1OC(=O)c2ccccc21>O>CC(O)CNC(=O)OCc1ccccc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9224b47530c142a5b1621a88637ebdc4
CC(=O)c1cc(N)ccc1Cl.CS(=O)(=O)Cl>>CC(=O)c1cc(NS(C)(=O)=O)ccc1Cl
NC=1C=CC(=C(C1)C(C)=O)Cl.CS(=O)(=O)Cl.O>>C(C)(=O)C=1C=C(C=CC1Cl)NS(=O)(=O)C
[CH3:1][C:2](=[O:3])[c:4]1[cH:5][c:6]([NH2:7])[cH:12][cH:13][c:14]1[Cl:15].Cl[S:8]([CH3:9])(=[O:10])=[O:11]>>[CH3:1][C:2](=[O:3])[c:4]1[cH:5][c:6]([NH:7][S:8]([CH3:9])(=[O:10])=[O:11])[cH:12][cH:13][c:14]1[Cl:15]
CC(=O)c1cc(N)ccc1Cl.CS(=O)(=O)Cl
CC(=O)c1cc(NS(C)(=O)=O)ccc1Cl
null
null
C1(=CC=CC=C1)C
Acylation
Sulfonamide synthesis (Schotten-Baumann) primary amine
4c44ef6d7646f6ef25dd125d2c32c713d8dcae7c603407faa5f0fb810631670e
8fce8115d8a725afa92eb3910ded29d4c852e5133eba78a425054f41f7142603
c1ccccc1
Cl-[S;H0;D4;+0:1](-[C;D1;H3:2])(=[O;D1;H0:3])=[O;D1;H0:4].[NH2;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[C;D1;H3:2]-[S;H0;D4;+0:1](=[O;D1;H0:3])(=[O;D1;H0:4])-[NH;D2;+0:5]-[c:6](:[c:7]):[c:8]
null
[]
null
null
50
MINUTE
1-(5-Amino-2-chlorophenyl)ethanone (411 mg; synthesized by the process reported by Radziejewski et al., Heterocycles, vol. 26, pp. 1227-1238, 1987) was dissolved in toluene (5 mL), and pyridine(235 μL) and methanesulfonyl chloride (225 μL) were added. The resulting mixture was stirred at room temperature for 50 minutes...
10.6084/m9.figshare.5104873.v1
null
Primary amine.Sulfonyl halide
Sulfonamide
null
null
c1ccccc1
HCl
C1(=CC=CC=C1)C
null
0.833333
CC(=O)c1cc(N)ccc1Cl.CS(=O)(=O)Cl>C1(=CC=CC=C1)C>CC(=O)c1cc(NS(C)(=O)=O)ccc1Cl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-88f3058c955b41cdbf67bba058084b87
BrBr.CC(=O)c1cc(NS(C)(=O)=O)ccc1Cl>>CS(=O)(=O)Nc1ccc(Cl)c(C(=O)CBr)c1
C(C)(=O)C=1C=C(C=CC1Cl)NS(=O)(=O)C.BrBr>>BrCC(=O)C=1C=C(C=CC1Cl)NS(=O)(=O)C
Br[Br:15].[CH3:1][S:2](=[O:3])(=[O:4])[NH:5][c:6]1[cH:7][cH:8][c:9]([Cl:10])[c:11]([C:12](=[O:13])[CH3:14])[cH:16]1>>[CH3:1][S:2](=[O:3])(=[O:4])[NH:5][c:6]1[cH:7][cH:8][c:9]([Cl:10])[c:11]([C:12](=[O:13])[CH2:14][Br:15])[cH:16]1
BrBr.CC(=O)c1cc(NS(C)(=O)=O)ccc1Cl
CS(=O)(=O)Nc1ccc(Cl)c(C(=O)CBr)c1
null
null
O1CCOCC1
Functional Group Interconversion
Bromination
97ca6720945af5a02c450d33ec56e946521050f9771c27f9cfcb85f3477593f6
cb3e14519230141aa015a4cf9c960def3e60f01997e61621f62506924bfa15de
c1ccccc1
Br-[Br;H0;D1;+0:1].[CH3;D1;+0:2]-[C:3](=[O;D1;H0:4])-[c:5]>>[Br;H0;D1;+0:1]-[CH2;D2;+0:2]-[C:3](=[O;D1;H0:4])-[c:5]
null
[]
null
null
1
HOUR
N-(3-acetyl-4-chlorophenyl)methanesulfonamide (300 mg) was dissolved in dioxane (5 mL), and bromine (77 μL) was added dropwise with ice-cooling. After stirring at room temperature for 1 hour, the solvent was distilled off under reduced pressure. The residue was washed with a water/ethanol mixture (1:1) and then dried u...
10.6084/m9.figshare.5104873.v1
null
Ketone
Primary halide
null
null
c1ccccc1
HBr
O1CCOCC1
null
1
BrBr.CC(=O)c1cc(NS(C)(=O)=O)ccc1Cl>O1CCOCC1>CS(=O)(=O)Nc1ccc(Cl)c(C(=O)CBr)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d8616594c0d04ca5a9f372657f02e4e1
CS(=O)(=O)Cl.Nc1cc(C(=O)c2ccccc2)cc([N+](=O)[O-])c1>>CC(=O)c1cc(NS(C)(=O)=O)cc([N+](=O)[O-])c1
O.NC=1C=C(C(=O)C2=CC=CC=C2)C=C(C1)[N+](=O)[O-].CS(=O)(=O)Cl.CS(=O)(=O)Cl>>C(C)(=O)C=1C=C(C=C(C1)[N+](=O)[O-])NS(=O)(=O)C
Cl[S:8]([CH3:9])(=[O:10])=[O:11].c1cc[c:1]([C:2](=[O:3])[c:4]2[cH:5][c:6]([NH2:7])[cH:12][c:13]([N+:14](=[O:15])[O-:16])[cH:17]2)cc1>>[CH3:1][C:2](=[O:3])[c:4]1[cH:5][c:6]([NH:7][S:8]([CH3:9])(=[O:10])=[O:11])[cH:12][c:13]([N+:14](=[O:15])[O-:16])[cH:17]1
CS(=O)(=O)Cl.Nc1cc(C(=O)c2ccccc2)cc([N+](=O)[O-])c1
CC(=O)c1cc(NS(C)(=O)=O)cc([N+](=O)[O-])c1
null
null
N1=CC=CC=C1
Acylation
OtherReaction
86cfa56c5c936672a8e8d7b1baae400b2d2392c6c11f99c71b83851b67486cc6
f84ee06fcaf2219fbd11c25e4c02a711528f4b8b23209196daa28d2a0a918e34
c1ccccc1
Cl-[S;H0;D4;+0:1](-[C;D1;H3:2])(=[O;D1;H0:3])=[O;D1;H0:4].[NH2;D1;+0:5]-[c:6](:[c:7]):[c:8]:[c:9]-[C:10](=[O;D1;H0:11])-[c;H0;D3;+0:12]1:c:c:c:c:c:1>>[C;D1;H3:2]-[S;H0;D4;+0:1](=[O;D1;H0:3])(=[O;D1;H0:4])-[NH;D2;+0:5]-[c:6](:[c:7]):[c:8]:[c:9]-[C:10](-[CH3;D1;+0:12])=[O;D1;H0:11]
null
[]
50
CELSIUS
2
HOUR
3-Amino-5-nitrobenzophenone (4 g; synthesized by the process reported by Berend et al., J. Prakt. Chem., vol. 69, p. 471 (1904)) was dissolved in pyridine (40 mL), and the temperature was maintained at 50° C. Methanesulfonyl chloride (1.9 mL) was added, followed by stirring for 2 hours. Additional methanesulfonyl chlor...
10.6084/m9.figshare.5104873.v1
null
Ketone.Primary amine.Sulfonyl halide
Sulfonamide.Ketone
c1ccccc1
null
c1ccccc1
HCl
N1=CC=CC=C1
50
2
CS(=O)(=O)Cl.Nc1cc(C(=O)c2ccccc2)cc([N+](=O)[O-])c1>N1=CC=CC=C1>CC(=O)c1cc(NS(C)(=O)=O)cc([N+](=O)[O-])c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-167ee1b3ddf04ba79ea3dfdb6e0c7ce9
BrBr.CC(=O)c1cc(Cl)cc(NS(C)(=O)=O)c1>>CS(=O)(=O)Nc1cc(Cl)cc(C(=O)CBr)c1
C(C)(=O)C=1C=C(C=C(C1)Cl)NS(=O)(=O)C.BrBr.O>>BrCC(=O)C=1C=C(C=C(C1)Cl)NS(=O)(=O)C
Br[Br:15].[CH3:1][S:2](=[O:3])(=[O:4])[NH:5][c:6]1[cH:7][c:8]([Cl:9])[cH:10][c:11]([C:12](=[O:13])[CH3:14])[cH:16]1>>[CH3:1][S:2](=[O:3])(=[O:4])[NH:5][c:6]1[cH:7][c:8]([Cl:9])[cH:10][c:11]([C:12](=[O:13])[CH2:14][Br:15])[cH:16]1
BrBr.CC(=O)c1cc(Cl)cc(NS(C)(=O)=O)c1
CS(=O)(=O)Nc1cc(Cl)cc(C(=O)CBr)c1
null
null
O1CCOCC1
Functional Group Interconversion
Bromination
97ca6720945af5a02c450d33ec56e946521050f9771c27f9cfcb85f3477593f6
cb3e14519230141aa015a4cf9c960def3e60f01997e61621f62506924bfa15de
c1ccccc1
Br-[Br;H0;D1;+0:1].[CH3;D1;+0:2]-[C:3](=[O;D1;H0:4])-[c:5]>>[Br;H0;D1;+0:1]-[CH2;D2;+0:2]-[C:3](=[O;D1;H0:4])-[c:5]
null
[]
50
CELSIUS
30
MINUTE
N-(3-acetyl-5-chlorophenyl)methanesulfonamide (500 mg) was dissolved in dioxane (10 mL). The temperature was maintained at 50° C. and bromine (0.11 mL) was added. After stirring for 30 minutes, water (50 mL) was added to the mixture, and the mixture was extracted with ethyl acetate (50 mL). The ethyl acetate layer was ...
10.6084/m9.figshare.5104873.v1
null
Ketone
Primary halide
null
null
c1ccccc1
HBr
O1CCOCC1
50
0.5
BrBr.CC(=O)c1cc(Cl)cc(NS(C)(=O)=O)c1>O1CCOCC1>CS(=O)(=O)Nc1cc(Cl)cc(C(=O)CBr)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1cb77ff985ea48bbb3a08fd858b47c30
CCOC(=O)c1[nH]c2cc(OC)ccc2c1C>>CCOC(=O)c1[nH]c2cc(O)ccc2c1C
CC1=C(NC2=CC(=CC=C12)OC)C(=O)OCC.B(Br)(Br)Br.O>>CC1=C(NC2=CC(=CC=C12)O)C(=O)OCC
C[O:11][c:10]1[cH:9][c:8]2[nH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:15]([CH3:16])[c:14]2[cH:13][cH:12]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[nH:7][c:8]2[cH:9][c:10]([OH:11])[cH:12][cH:13][c:14]2[c:15]1[CH3:16]
CCOC(=O)c1[nH]c2cc(OC)ccc2c1C
CCOC(=O)c1[nH]c2cc(O)ccc2c1C
null
null
C(Cl)Cl
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2[nH]ccc2c1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]:[c:2](-[OH;D1;+0:1]):[c:3]
null
[]
null
null
40
MINUTE
Ethyl 3-methyl-6-methoxy-1H-indole-2-carboxylate (1.00 g; synthesized according to the disclosures in the literature (Gan et al., J. Org. Chem., vol. 62, pp. 9298-9304, 1997)) was dissolved in methylene chloride (dehydrated, 13 mL), and boron tribromide (1 M/methylene chloride, 17.2 mL) was added dropwise under ice-coo...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccc2[nH]ccc2c1
Other
C(Cl)Cl
null
0.666667
CCOC(=O)c1[nH]c2cc(OC)ccc2c1C>C(Cl)Cl>CCOC(=O)c1[nH]c2cc(O)ccc2c1C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c1db8e4ae1b249e1809a6b8b9ce4932b
COCCN.O=C/C=C/c1ccccc1.O=Cc1ccc(C=CC(=O)O)cc1>>COCCN(CC=Cc1ccccc1)Cc1ccc(C=CC(=O)O)cc1
C(=O)C1=CC=C(C=CC(=O)O)C=C1.C(\C=C\C1=CC=CC=C1)=O.[BH-](OC(=O)C)(OC(=O)C)OC(=O)C.[Na+].C(C)(C)N=C=NC(C)C.COCCN.[BH-](OC(=O)C)(OC(=O)C)OC(=O)C.[Na+]>>COCCN(CC=CC1=CC=CC=C1)CC1=CC=C(C=C1)C=CC(=O)O
[CH3:1][O:2][CH2:3][CH2:4][NH2:5].O=[CH:6]/[CH:7]=[CH:8]/[c:9]1[cH:10][cH:11][cH:12][cH:13][cH:14]1.O=[CH:15][c:16]1[cH:17][cH:18][c:19]([CH:20]=[CH:21][C:22](=[O:23])[OH:24])[cH:25][cH:26]1>>[CH3:1][O:2][CH2:3][CH2:4][N:5]([CH2:6][CH:7]=[CH:8][c:9]1[cH:10][cH:11][cH:12][cH:13][cH:14]1)[CH2:15][c:16]1[cH:17][cH:18][c:1...
COCCN.O=C/C=C/c1ccccc1.O=Cc1ccc(C=CC(=O)O)cc1
COCCN(CC=Cc1ccccc1)Cc1ccc(C=CC(=O)O)cc1
null
CN(C)C=1C=CN=CC1
C(C)(=O)O.CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
caeb34b0d1f507fdfdad7625809efaadf272ca1e3abe9fad823e5db43af42099
c96547fa32f6396bf2b14895e43dd5251c6f158a37edf6d969dcd15090496e48
C(=Cc1ccccc1)CNCc1ccccc1
O=[CH;D2;+0:1]-[c:2](:[c:3]):[c:4].O=[CH;D2;+0:5]/[C:6]=[C:7]/[c:8](:[c:9]):[c:10].[C:11]-[C:12]-[NH2;D1;+0:13]>>[C:11]-[C:12]-[N;H0;D3;+0:13](-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4])-[CH2;D2;+0:5]-[C:6]=[C:7]-[c:8](:[c:9]):[c:10]
null
[]
null
null
24
HOUR
Wang resin (1.1 mmol/g, 1.00 g) in a polypropylene filtration tube with a polyethylene frit was added DMF (5 mL) and CH2Cl2 (5 mL), followed by 4-formylcinnamic acid (5.5 mmol, 969 mg), DMAP (1.08 mmol, 132 mg) and diisopropylcarbodiimide (5.5 mmol, 861 μL). The mixture was shaken at room temperature for 24 hours. The ...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Aldehyde.Primary amine
Tertiary amine
null
null
c1ccccc1.c1ccccc1
Other
CN(C)C=1C=CN=CC1.C(C)(=O)O.CN(C)C=O
null
24
COCCN.O=C/C=C/c1ccccc1.O=Cc1ccc(C=CC(=O)O)cc1>CN(C)C=1C=CN=CC1.C(C)(=O)O.CN(C)C=O>COCCN(CC=Cc1ccccc1)Cc1ccc(C=CC(=O)O)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-894fa63debf248a0848b52c2557f1b54
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(O)c(C(=O)O)c1>>O=C(O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1O
NC1=CC=C(C(C(=O)O)=C1)O.C(C)N(CC)CC.FC1=C(CBr)C(=C(C(=C1F)C(F)(F)F)F)F>>OC1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F
Br[CH2:8][c:9]1[c:10]([F:11])[c:12]([F:13])[c:14]([C:15]([F:16])([F:17])[F:18])[c:19]([F:20])[c:21]1[F:22].[O:1]=[C:2]([OH:3])[c:4]1[cH:5][c:6]([NH2:7])[cH:23][cH:24][c:25]1[OH:26]>>[O:1]=[C:2]([OH:3])[c:4]1[cH:5][c:6]([NH:7][CH2:8][c:9]2[c:10]([F:11])[c:12]([F:13])[c:14]([C:15]([F:16])([F:17])[F:18])[c:19]([F:20])[c:2...
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(O)c(C(=O)O)c1
O=C(O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1O
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
N-alkylation of primary amines with alkyl halides
fc19a1445ff204e66e51735d0191465bda3c6691fd233624a54742c9d4828411
0b1d32f56ad00f1e5bdae9390f9227bbea012fa2f8203aac34726b8a6761cc7c
c1ccc(CNc2ccccc2)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[NH2;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[c:3]:[c:2](-[CH2;D2;+0:1]-[NH;D2;+0:5]-[c:6](:[c:7]):[c:8]):[c:4]
64
[{"value": 64.0, "product": "OC1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 62.7, "product": "OC1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
To a solution of 5-aminosalicylic acid (1.02 g, 6.66 mmole, purchased from Aldrich Chemical Company, USA, A7, 980-9) and triethylamine (1 ml) in dried DMF (80 ml) was added 2,3,5,6-tetrafluoro-4-trifluoromethylbenzyl bromide (1.23 g, 7.18 mmole) (Aldrich, 40, 640-6) at room temperature under a nitrogen atmosphere. The ...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Primary amine
Secondary amine
null
null
c1ccccc1.c1ccccc1
HBr
CN(C)C=O
null
2
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(O)c(C(=O)O)c1>CN(C)C=O>O=C(O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a5cc683afae54cf789ffec9dbcebb847
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc([N+](=O)[O-])c(C(=O)O)c1>>O=C(O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1[N+](=O)[O-]
NC=1C=CC(=C(C(=O)O)C1)[N+](=O)[O-].FC1=C(CBr)C(=C(C(=C1F)C(F)(F)F)F)F>>[N+](=O)([O-])C1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F
Br[CH2:8][c:9]1[c:10]([F:11])[c:12]([F:13])[c:14]([C:15]([F:16])([F:17])[F:18])[c:19]([F:20])[c:21]1[F:22].[O:1]=[C:2]([OH:3])[c:4]1[cH:5][c:6]([NH2:7])[cH:23][cH:24][c:25]1[N+:26](=[O:27])[O-:28]>>[O:1]=[C:2]([OH:3])[c:4]1[cH:5][c:6]([NH:7][CH2:8][c:9]2[c:10]([F:11])[c:12]([F:13])[c:14]([C:15]([F:16])([F:17])[F:18])[c...
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc([N+](=O)[O-])c(C(=O)O)c1
O=C(O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1[N+](=O)[O-]
null
null
null
Heteroatom Alkylation and Arylation
N-alkylation of primary amines with alkyl halides
fc19a1445ff204e66e51735d0191465bda3c6691fd233624a54742c9d4828411
0b1d32f56ad00f1e5bdae9390f9227bbea012fa2f8203aac34726b8a6761cc7c
c1ccc(CNc2ccccc2)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[NH2;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[c:3]:[c:2](-[CH2;D2;+0:1]-[NH;D2;+0:5]-[c:6](:[c:7]):[c:8]):[c:4]
76.3
[{"value": 76.3, "product": "[N+](=O)([O-])C1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 64.4, "product": "[N+](=O)([O-])C1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
According to the similar procedure in Synthesis Example 1, by using 5-amino-2-nitrobenzoic acid (1.03 g, 5.65 mmole) and 2,3,5,6-tetrafluoro-4-trifluoromethylbenzyl bromide (1.01 g, 6.04 mmole) (ACROS, 33074-0010), 1.50 g (76.3% yield) of 2-nitro-5-(2,3,5,6-tetrafluoro-4-trifluoromethylbenzylamino)benzoic acid was obta...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Primary amine
Secondary amine
null
null
c1ccccc1.c1ccccc1
HBr
null
null
null
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc([N+](=O)[O-])c(C(=O)O)c1>>O=C(O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1[N+](=O)[O-]
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c222045ee2aa408eb0a418c65a946bf8
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(Cl)c(C(=O)O)c1>>O=C(O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1Cl
NC=1C=CC(=C(C(=O)O)C1)Cl.FC1=C(CBr)C(=C(C(=C1F)C(F)(F)F)F)F>>ClC1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F
Br[CH2:8][c:9]1[c:10]([F:11])[c:12]([F:13])[c:14]([C:15]([F:16])([F:17])[F:18])[c:19]([F:20])[c:21]1[F:22].[O:1]=[C:2]([OH:3])[c:4]1[cH:5][c:6]([NH2:7])[cH:23][cH:24][c:25]1[Cl:26]>>[O:1]=[C:2]([OH:3])[c:4]1[cH:5][c:6]([NH:7][CH2:8][c:9]2[c:10]([F:11])[c:12]([F:13])[c:14]([C:15]([F:16])([F:17])[F:18])[c:19]([F:20])[c:2...
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(Cl)c(C(=O)O)c1
O=C(O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1Cl
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
N-alkylation of primary amines with alkyl halides
fc19a1445ff204e66e51735d0191465bda3c6691fd233624a54742c9d4828411
0b1d32f56ad00f1e5bdae9390f9227bbea012fa2f8203aac34726b8a6761cc7c
c1ccc(CNc2ccccc2)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[NH2;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[c:3]:[c:2](-[CH2;D2;+0:1]-[NH;D2;+0:5]-[c:6](:[c:7]):[c:8]):[c:4]
85.5
[{"value": 85.5, "product": "ClC1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 85.5, "product": "ClC1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
According to the similar procedure in Synthesis Example 1, by using 5-amino-2-chlorobenzoic acid (1.02 g, 5.94 mmole) (ACROS, 32525-5000), DMF (50 ml) and 2,3,5,6-tetrafluoro-4-trifluoromethylbenzyl bromide (1.16 g, 6.99 mmole), 2.04 g (85.5% yield) of 2-chloro-5-(2,3,5,6-tetrafluoro-4-trifluoromethylbenzylamino) benzo...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Primary amine
Secondary amine
null
null
c1ccccc1.c1ccccc1
HBr
CN(C)C=O
null
null
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(Cl)c(C(=O)O)c1>CN(C)C=O>O=C(O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1Cl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-390fd609b2054e69bd19397089e74dbd
O=C(O)c1cc([N+](=O)[O-])ccc1Br>>Nc1ccc(Br)c(C(=O)O)c1
BrC1=C(C(=O)O)C=C(C=C1)[N+](=O)[O-].[H][H]>>NC=1C=CC(=C(C(=O)O)C1)Br
O=[N+:1]([O-])[c:2]1[cH:3][cH:4][c:5]([Br:6])[c:7]([C:8](=[O:9])[OH:10])[cH:11]1>>[NH2:1][c:2]1[cH:3][cH:4][c:5]([Br:6])[c:7]([C:8](=[O:9])[OH:10])[cH:11]1
O=C(O)c1cc([N+](=O)[O-])ccc1Br
Nc1ccc(Br)c(C(=O)O)c1
null
[Pd]
CO
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccccc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
91.2
[{"value": 91.2, "product": "NC=1C=CC(=C(C(=O)O)C1)Br", "details": "PERCENTYIELD", "is_desired": false}, {"value": 91.2, "product": "NC=1C=CC(=C(C(=O)O)C1)Br", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A mixture of 2-bromo-5-nitrobenzoic acid (1.10 g, 4.06 mmol) (Aldrich, 38, 184-5), activated Pd—C (43.62 mg, 0.41 mmol) (Aldrich, 20, 569-9) in methanol (30 ml) was hydrogenated for 4 hr under 30 psi of hydrogen pressure. After the mixture was filtered, the filtrate was concentrated to give 0.80 g (91.2% yield) of 5-am...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccccc1
Other
[Pd].CO
null
null
O=C(O)c1cc([N+](=O)[O-])ccc1Br>[Pd].CO>Nc1ccc(Br)c(C(=O)O)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8676b9e4f09b4e87b386240126c3f4b1
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(Br)c(C(=O)O)c1>>O=C(O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1Br
NC=1C=CC(=C(C(=O)O)C1)Br.FC1=C(CBr)C(=C(C(=C1F)C(F)(F)F)F)F>>BrC1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F
Br[CH2:8][c:9]1[c:10]([F:11])[c:12]([F:13])[c:14]([C:15]([F:16])([F:17])[F:18])[c:19]([F:20])[c:21]1[F:22].[O:1]=[C:2]([OH:3])[c:4]1[cH:5][c:6]([NH2:7])[cH:23][cH:24][c:25]1[Br:26]>>[O:1]=[C:2]([OH:3])[c:4]1[cH:5][c:6]([NH:7][CH2:8][c:9]2[c:10]([F:11])[c:12]([F:13])[c:14]([C:15]([F:16])([F:17])[F:18])[c:19]([F:20])[c:2...
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(Br)c(C(=O)O)c1
O=C(O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1Br
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
N-alkylation of primary amines with alkyl halides
fc19a1445ff204e66e51735d0191465bda3c6691fd233624a54742c9d4828411
0b1d32f56ad00f1e5bdae9390f9227bbea012fa2f8203aac34726b8a6761cc7c
c1ccc(CNc2ccccc2)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[NH2;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[c:3]:[c:2](-[CH2;D2;+0:1]-[NH;D2;+0:5]-[c:6](:[c:7]):[c:8]):[c:4]
76.9
[{"value": 76.9, "product": "BrC1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 74.0, "product": "BrC1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
According to the similar procedure in Synthesis Example 1, by using 5-amino-2-bromobenzoic acid (1.05 g, 6.12 mmole) which was prepared from Synthesis Example (4-1), DMF (50 ml) and 2,3,5,6-tetrafluoro-4-trifluoromethylbenzyl bromide (1.16 g, 6.99 mmole), 2.02 g (76.9% yield) of 2-bromo-5-(2,3,5,6-tetrafluoro-4-trifluo...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Primary amine
Secondary amine
null
null
c1ccccc1.c1ccccc1
HBr
CN(C)C=O
null
null
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(Br)c(C(=O)O)c1>CN(C)C=O>O=C(O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1Br
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-750e61fe796f4854bdffb6a3e69937e5
Cc1ccc(N)cc1C(=O)O.Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr>>Cc1ccc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)cc1C(=O)O
NC=1C=CC(=C(C(=O)O)C1)C.FC1=C(CBr)C(=C(C(=C1F)C(F)(F)F)F)F>>CC1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F
[CH3:1][c:2]1[cH:3][cH:4][c:5]([NH2:6])[cH:22][c:23]1[C:24](=[O:25])[OH:26].Br[CH2:7][c:8]1[c:9]([F:10])[c:11]([F:12])[c:13]([C:14]([F:15])([F:16])[F:17])[c:18]([F:19])[c:20]1[F:21]>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([NH:6][CH2:7][c:8]2[c:9]([F:10])[c:11]([F:12])[c:13]([C:14]([F:15])([F:16])[F:17])[c:18]([F:19])[c:20]2[F:...
Cc1ccc(N)cc1C(=O)O.Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr
Cc1ccc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)cc1C(=O)O
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
N-alkylation of primary amines with alkyl halides
fc19a1445ff204e66e51735d0191465bda3c6691fd233624a54742c9d4828411
0b1d32f56ad00f1e5bdae9390f9227bbea012fa2f8203aac34726b8a6761cc7c
c1ccc(CNc2ccccc2)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[NH2;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[c:3]:[c:2](-[CH2;D2;+0:1]-[NH;D2;+0:5]-[c:6](:[c:7]):[c:8]):[c:4]
27
[{"value": 27.0, "product": "CC1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 26.2, "product": "CC1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
According to the similar procedure in Synthesis Example 1, by using 5-amino-2-methylbenzoic acid (2.06 g, 15.0 mmole), DMF (60 ml), TEA (4 ml), and 2,3,5,6-tetrafluoro-4-trifluoromethylbenzyl bromide (5.52 ml, 17.7 mmole), 1.50 g (27.0% yield) of 2-methyl-5-(2,3,5,6-tetrafluoro-4-trifluoromethylbenzylamino)benzoic acid...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Primary amine
Secondary amine
null
null
c1ccccc1.c1ccccc1
HBr
CN(C)C=O
null
null
Cc1ccc(N)cc1C(=O)O.Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr>CN(C)C=O>Cc1ccc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)cc1C(=O)O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-293ed785b3c94f7a8958f37859fb86e4
COc1ccc(N)cc1C(=O)O.Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr>>COc1ccc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)cc1C(=O)O
NC=1C=CC(=C(C(=O)O)C1)OC.FC1=C(CBr)C(=C(C(=C1F)C(F)(F)F)F)F>>COC1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F
[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([NH2:7])[cH:23][c:24]1[C:25](=[O:26])[OH:27].Br[CH2:8][c:9]1[c:10]([F:11])[c:12]([F:13])[c:14]([C:15]([F:16])([F:17])[F:18])[c:19]([F:20])[c:21]1[F:22]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([NH:7][CH2:8][c:9]2[c:10]([F:11])[c:12]([F:13])[c:14]([C:15]([F:16])([F:17])[F:18])[c:19]([F:20...
COc1ccc(N)cc1C(=O)O.Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr
COc1ccc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)cc1C(=O)O
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
N-alkylation of primary amines with alkyl halides
fc19a1445ff204e66e51735d0191465bda3c6691fd233624a54742c9d4828411
0b1d32f56ad00f1e5bdae9390f9227bbea012fa2f8203aac34726b8a6761cc7c
c1ccc(CNc2ccccc2)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[NH2;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[c:3]:[c:2](-[CH2;D2;+0:1]-[NH;D2;+0:5]-[c:6](:[c:7]):[c:8]):[c:4]
31.5
[{"value": 31.5, "product": "COC1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 29.7, "product": "COC1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
According to the similar procedure in Synthesis Example 1, by using 5-amino-2-methoxy-benzoic acid (2.10 g, 12.7 mmole), DMF (50 ml), TEA (6 ml), and 2,3,5,6-tetrafluoro-4-trifluoromethylbenzyl bromide (2.00 ml, 14.0 mmole), 1.50 g (31.5% yield) of 2-methoxy-5-(2,3,5,6-tetrafluoro-4-trifluoromethylbenzylamino)benzoic a...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Primary amine
Secondary amine
null
null
c1ccccc1.c1ccccc1
HBr
CN(C)C=O
null
null
COc1ccc(N)cc1C(=O)O.Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr>CN(C)C=O>COc1ccc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)cc1C(=O)O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3c88871a490b486ba1336b695bd24fe1
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(OC(F)(F)F)c(C(=O)O)c1>>O=C(O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1OC(F)(F)F
NC=1C=CC(=C(C(=O)O)C1)OC(F)(F)F.FC1=C(CBr)C(=C(C(=C1F)C(F)(F)F)F)F>>FC1=C(CNC=2C=CC(=C(C(=O)O)C2)OC(F)(F)F)C(=C(C(=C1F)C(F)(F)F)F)F
Br[CH2:8][c:9]1[c:10]([F:11])[c:12]([F:13])[c:14]([C:15]([F:16])([F:17])[F:18])[c:19]([F:20])[c:21]1[F:22].[O:1]=[C:2]([OH:3])[c:4]1[cH:5][c:6]([NH2:7])[cH:23][cH:24][c:25]1[O:26][C:27]([F:28])([F:29])[F:30]>>[O:1]=[C:2]([OH:3])[c:4]1[cH:5][c:6]([NH:7][CH2:8][c:9]2[c:10]([F:11])[c:12]([F:13])[c:14]([C:15]([F:16])([F:17...
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(OC(F)(F)F)c(C(=O)O)c1
O=C(O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1OC(F)(F)F
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
N-alkylation of primary amines with alkyl halides
fc19a1445ff204e66e51735d0191465bda3c6691fd233624a54742c9d4828411
0b1d32f56ad00f1e5bdae9390f9227bbea012fa2f8203aac34726b8a6761cc7c
c1ccc(CNc2ccccc2)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[NH2;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[c:3]:[c:2](-[CH2;D2;+0:1]-[NH;D2;+0:5]-[c:6](:[c:7]):[c:8]):[c:4]
81
[{"value": 81.0, "product": "FC1=C(CNC=2C=CC(=C(C(=O)O)C2)OC(F)(F)F)C(=C(C(=C1F)C(F)(F)F)F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 80.0, "product": "FC1=C(CNC=2C=CC(=C(C(=O)O)C2)OC(F)(F)F)C(=C(C(=C1F)C(F)(F)F)F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
According to the similar procedure in Synthesis Example 1, by using 5-amino-2-trifluoromethoxybenzoic acid (1.35 g, 6.23 mmole), DMF (50 ml), TEA (6 ml), and 2,3,5,6-tetrafluoro-4-trifluoromethylbenzyl bromide (1.10 ml, 6.73 mmole), 2.25 g (81.0% yield) of 5-(2,3,5,6-tetrafluoro-4-trifluoromethylbenzylamino)-2-trifluor...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Primary amine
Secondary amine
null
null
c1ccccc1.c1ccccc1
HBr
CN(C)C=O
null
null
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(OC(F)(F)F)c(C(=O)O)c1>CN(C)C=O>O=C(O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1OC(F)(F)F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5e87e5d373204b00a309bcf30e191c85
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(O)c([N+](=O)[O-])c1>>O=[N+]([O-])c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1O
NC1=CC(=C(C=C1)O)[N+](=O)[O-].FC1=C(CBr)C(=C(C(=C1F)C(F)(F)F)F)F>>[N+](=O)([O-])C1=C(C=CC(=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F)O
Br[CH2:8][c:9]1[c:10]([F:11])[c:12]([F:13])[c:14]([C:15]([F:16])([F:17])[F:18])[c:19]([F:20])[c:21]1[F:22].[O:1]=[N+:2]([O-:3])[c:4]1[cH:5][c:6]([NH2:7])[cH:23][cH:24][c:25]1[OH:26]>>[O:1]=[N+:2]([O-:3])[c:4]1[cH:5][c:6]([NH:7][CH2:8][c:9]2[c:10]([F:11])[c:12]([F:13])[c:14]([C:15]([F:16])([F:17])[F:18])[c:19]([F:20])[c...
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(O)c([N+](=O)[O-])c1
O=[N+]([O-])c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1O
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
N-alkylation of primary amines with alkyl halides
fc19a1445ff204e66e51735d0191465bda3c6691fd233624a54742c9d4828411
0b1d32f56ad00f1e5bdae9390f9227bbea012fa2f8203aac34726b8a6761cc7c
c1ccc(CNc2ccccc2)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[NH2;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[c:3]:[c:2](-[CH2;D2;+0:1]-[NH;D2;+0:5]-[c:6](:[c:7]):[c:8]):[c:4]
40.1
[{"value": 40.0, "product": "[N+](=O)([O-])C1=C(C=CC(=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 40.1, "product": "[N+](=O)([O-])C1=C(C=CC(=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
According to the similar procedure in Synthesis Example 1, by using 4-amino-2-nitrophenol (1.00 g, 6.49 mmole), DMF (30 ml), TEA (0.5 ml), and 2,3,5,6-tetrafluoro-4-trifluoromethylbenzyl bromide (1.30 g, 7.78 mmole), 1.00 g (40.0% yield) of 2-nitro-4-(2,3,5,6-tetrafluoro-4-trifluoromethylbenzylamino)phenol was obtained...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Primary amine
Secondary amine
null
null
c1ccccc1.c1ccccc1
HBr
CN(C)C=O
null
null
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(O)c([N+](=O)[O-])c1>CN(C)C=O>O=[N+]([O-])c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d5107375989e46bfbb8c0e6718b327ab
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(O)c(Cl)c1>>Cc1c(F)c(F)c(CNc2ccc(Cl)c(O)c2)c(F)c1F
CN(C)C=O.NC1=CC(=C(C=C1)O)Cl.FC1=C(CBr)C(=C(C(=C1F)C(F)(F)F)F)F>>ClC1=C(C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C)F)F)O
F[C:1](F)(F)[c:2]1[c:3]([F:4])[c:5]([F:6])[c:7]([CH2:8]Br)[c:18]([F:19])[c:20]1[F:21].[NH2:9][c:10]1[cH:11][cH:12][c:13]([OH:16])[c:15]([Cl:14])[cH:17]1>>[CH3:1][c:2]1[c:3]([F:4])[c:5]([F:6])[c:7]([CH2:8][NH:9][c:10]2[cH:11][cH:12][c:13]([Cl:14])[c:15]([OH:16])[cH:17]2)[c:18]([F:19])[c:20]1[F:21]
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(O)c(Cl)c1
Cc1c(F)c(F)c(CNc2ccc(Cl)c(O)c2)c(F)c1F
null
null
null
Functional Group Interconversion
OtherReaction
2f5fbc13bfdd659219d4acdbee0ba26495de3c7de2f9d8b612cbb13c8b331405
3c5408e040084c21855dd371e440694eff7bc6aaa42a994d1e1f5aa792221f78
c1ccc(CNc2ccccc2)cc1
Br-[CH2;D2;+0:1]-[c:2]1:[c:3]:[c:4]:[c:5](-[C;H0;D4;+0:6](-F)(-F)-F):[c:7]:[c:8]:1.[Cl;H0;D1;+0:9]-[c;H0;D3;+0:10]1:[c:11]:[c:12](-[NH2;D1;+0:13]):[c:14]:[c:15]:[c;H0;D3;+0:16]:1-[OH;D1;+0:17]>>[CH3;D1;+0:6]-[c:5]1:[c:4]:[c:3]:[c:2](-[CH2;D2;+0:1]-[NH;D2;+0:13]-[c:12]2:[c:14]:[c:15]:[c;H0;D3;+0:16](-[Cl;H0;D1;+0:9]):[c...
76
[{"value": 76.0, "product": "ClC1=C(C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C)F)F)O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
According to the similar procedure in Synthesis Example 1, by using 4-amino-2-chlorophenol (3.00 g, 19.6 mmole), DMF (80 ml), TEA (0.5 ml), and 2,3,5,6-tetrafluoro-4-trifluoromethylbenzyl bromide (1.40 g, 8.36 mmole), 2.00 g (76.0% yield) of 2-chloro-5-(2,3,5,6-tetrafluoro-4-methylbenzylamino)phenol was obtained as a y...
10.6084/m9.figshare.5104873.v1
null
Trifluoro group.Aromatic halide.Primary halide.Aromatic alcohol.Primary amine
Aromatic halide.Aromatic alcohol.Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
Br-
null
null
null
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(O)c(Cl)c1>>Cc1c(F)c(F)c(CNc2ccc(Cl)c(O)c2)c(F)c1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-66851f08c5224104813f8dba4d0abb62
NC(=O)c1cc(N(Cc2c(F)c(F)c(C(F)(F)F)c(F)c2F)C(=O)C(F)(F)F)ccc1OC(=O)C(F)(F)F>>NC(=O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1O
FC(C(=O)OC1=C(C=C(C=C1)N(C(C(F)(F)F)=O)CC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F)C(N)=O)(F)F>>OC1=C(C(=O)N)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F
O=C(C(F)(F)F)[N:7]([c:6]1[cH:5][c:4]([C:2]([NH2:1])=[O:3])[c:25]([O:26]C(=O)C(F)(F)F)[cH:24][cH:23]1)[CH2:8][c:9]1[c:10]([F:11])[c:12]([F:13])[c:14]([C:15]([F:16])([F:17])[F:18])[c:19]([F:20])[c:21]1[F:22]>>[NH2:1][C:2](=[O:3])[c:4]1[cH:5][c:6]([NH:7][CH2:8][c:9]2[c:10]([F:11])[c:12]([F:13])[c:14]([C:15]([F:16])([F:17]...
NC(=O)c1cc(N(Cc2c(F)c(F)c(C(F)(F)F)c(F)c2F)C(=O)C(F)(F)F)ccc1OC(=O)C(F)(F)F
NC(=O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1O
null
null
O.CO
Reduction
OtherReaction
e732b2e4043397b4d449cd428dab168843bdc776f00bc9fc33f856fcf51f73d9
7306b7444ac76569af96bfc353474db991eabf13620e7820935e2aec88c27ee1
c1ccc(CNc2ccccc2)cc1
F-C(-F)(-F)-C(=O)-[O;H0;D2;+0:1]-[c:2]1:[c:3]:[c:4]:[c:5](-[N;H0;D3;+0:6](-[C:7]-[c:8])-C(=O)-C(-F)(-F)-F):[c:9]:[c:10]:1-[C:11](-[N;D1;H2:12])=[O;D1;H0:13]>>[N;D1;H2:12]-[C:11](=[O;D1;H0:13])-[c:10]1:[c:9]:[c:5](-[NH;D2;+0:6]-[C:7]-[c:8]):[c:4]:[c:3]:[c:2]:1-[OH;D1;+0:1]
60.4
[{"value": 60.0, "product": "OC1=C(C(=O)N)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 60.4, "product": "OC1=C(C(=O)N)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
24
HOUR
To a solution of 2-carbamoyl-4-[2,3,5,6-tetrafluoro-4-trifluoromethylbenzyl-(2,2,2-trifluoroacetyl)amino]phenyl trifluoroacetate (300 mg, 0.52 mmole) in methanol (8 ml) and water (3 ml) was added c-HCl (2.0 ml) at 40° C. under a nitrogen atmosphere. After the reaction mixture was stirred for 24 hr, the organic solvent ...
10.6084/m9.figshare.5104873.v1
null
Trifluoro group.Trifluoro group.Ester.Tertiary amide
Aromatic alcohol.Secondary amine
null
null
c1ccccc1.c1ccccc1
Other
O.CO
null
24
NC(=O)c1cc(N(Cc2c(F)c(F)c(C(F)(F)F)c(F)c2F)C(=O)C(F)(F)F)ccc1OC(=O)C(F)(F)F>O.CO>NC(=O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e4fa4aa1191e49bdb2e5eef8bfebf1e1
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(S(=O)(=O)O)c(O)c1>>O=S(=O)(O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1O
CN(C)C=O.NC1=CC(=C(C=C1)S(=O)(=O)O)O.FC1=C(CBr)C(=C(C(=C1F)C(F)(F)F)F)F>>OC1=C(C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F)S(=O)(=O)O
Br[CH2:9][c:10]1[c:11]([F:12])[c:13]([F:14])[c:15]([C:16]([F:17])([F:18])[F:19])[c:20]([F:21])[c:22]1[F:23].[O:1]=[S:2](=[O:3])([OH:4])[c:5]1[cH:25][cH:24][c:7]([NH2:8])[cH:6][c:26]1[OH:27]>>[O:1]=[S:2](=[O:3])([OH:4])[c:5]1[cH:6][c:7]([NH:8][CH2:9][c:10]2[c:11]([F:12])[c:13]([F:14])[c:15]([C:16]([F:17])([F:18])[F:19])...
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(S(=O)(=O)O)c(O)c1
O=S(=O)(O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1O
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
fb14e376a8ea411d1b814ae4d8f85eb9e6fad53469f2e0ef9107e3c147574d24
7f961f9f63fb19401b9cb6ccb23b7f9357060620e96238b4ca2454442616e763
c1ccc(CNc2ccccc2)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[NH2;D1;+0:5]-[c:6]1:[c:7]:[cH;D2;+0:8]:[c;H0;D3;+0:9](-[#16:10](=[O;D1;H0:11])(=[O;D1;H0:12])-[O;D1;H1:13]):[c;H0;D3;+0:14](-[O;D1;H1:15]):[cH;D2;+0:16]:1>>[O;D1;H0:11]=[#16:10](=[O;D1;H0:12])(-[O;D1;H1:13])-[c;H0;D3;+0:9]1:[cH;D2;+0:16]:[c:6](-[NH;D2;+0:5]-[CH2;D2;+0:1]-[c:2](:[c:...
28
[{"value": 28.0, "product": "OC1=C(C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F)S(=O)(=O)O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
According to the similar procedure in Synthesis Example 1, by using 4-amino-2-hydroxybenzene sulfonic acid (1.00 g, 5.30 mmole), DMF (10 ml), TEA (1.0 ml), and 2,3,5,6-tetrafluoro-4-trifluoromethylbenzyl bromide (0.88 g, 5.30 mmole), 0.61 g (28.0% yield) of 2-hydroxy-5-(2,3,5,6-tetrafluoro-4-trifluoromethylbenzylamino)...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol.Primary amine
Aromatic alcohol.Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HBr
null
null
null
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(S(=O)(=O)O)c(O)c1>>O=S(=O)(O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-43cc6966ac17402492f3a6f82d958b8e
CO.Nc1ccc(O)c(C(=O)O)c1>>COC(=O)c1cc(N)ccc1O
NC1=CC=C(C(C(=O)O)=C1)O.CO>>NC=1C=CC(=C(C(=O)OC)C1)O
[CH3:1][OH:2].O[C:3](=[O:4])[c:5]1[cH:6][c:7]([NH2:8])[cH:9][cH:10][c:11]1[OH:12]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][c:7]([NH2:8])[cH:9][cH:10][c:11]1[OH:12]
CO.Nc1ccc(O)c(C(=O)O)c1
COC(=O)c1cc(N)ccc1O
null
null
null
Protection
Esterification of Carboxylic Acids
9cecdbd189c6f9c3648521d17154d013842a5498de4e76e65efb1d842973340b
af0b8064f2e82ebe66c4c29d2391785ac1b993104265ccdc4d67ca79e36fa3c8
c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C;D1;H3:6]-[OH;D1;+0:7]>>[C;D1;H3:6]-[O;H0;D2;+0:7]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
76
[{"value": 76.0, "product": "NC=1C=CC(=C(C(=O)OC)C1)O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of 5-aminosalicylic acid (3.00 g, 19.6 mmole) in methanol (80 ml) was added c-H2SO4 (8 ml) at 0° C. After the reaction mixture was refluxed for 6 hr, the solvent was removed in vacuo. The resulting residue was partitioned with ethyl acetate and water. The organic layer was washed with water (40 ml×3) and ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Methanol
Ester
null
null
c1ccccc1
HO-
null
null
null
CO.Nc1ccc(O)c(C(=O)O)c1>>COC(=O)c1cc(N)ccc1O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-83e2a5dadaef4015baabb40fa38b9712
CC(=O)Cl.CC(C)(C)OC(=O)Nc1ccc(O)c(C(=O)O)c1>>CC(=O)Oc1ccc(NC(=O)OC(C)(C)C)cc1C(=O)O
C(C)(C)(C)OC(=O)NC=1C=CC(=C(C(=O)O)C1)O.C(C)(=O)Cl.C([O-])([O-])=O.[K+].[K+]>>C(C)(=O)OC1=C(C(=O)O)C=C(C=C1)NC(=O)OC(C)(C)C
Cl[C:2]([CH3:1])=[O:3].[OH:4][c:5]1[cH:6][cH:7][c:8]([NH:9][C:10](=[O:11])[O:12][C:13]([CH3:14])([CH3:15])[CH3:16])[cH:17][c:18]1[C:19](=[O:20])[OH:21]>>[CH3:1][C:2](=[O:3])[O:4][c:5]1[cH:6][cH:7][c:8]([NH:9][C:10](=[O:11])[O:12][C:13]([CH3:14])([CH3:15])[CH3:16])[cH:17][c:18]1[C:19](=[O:20])[OH:21]
CC(=O)Cl.CC(C)(C)OC(=O)Nc1ccc(O)c(C(=O)O)c1
CC(=O)Oc1ccc(NC(=O)OC(C)(C)C)cc1C(=O)O
null
null
CN(C)C=O
Acylation
Schotten-Baumann to ester
1cda078f55e64d9385e544d1067595d5e7672bbd1eff542e7a341817a2d8c4d5
6439fc27f97ee9ed7c11ef9b5032d9493d05f28a7bbb50d256a2d54d035fbfb2
c1ccccc1
Cl-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[O;D1;H0:4]=[C:5](-[O;D1;H1:6])-[c:7]:[c:8](-[OH;D1;+0:9]):[c:10]>>[C;D1;H3:2]-[C;H0;D3;+0:1](=[O;D1;H0:3])-[O;H0;D2;+0:9]-[c:8](:[c:10]):[c:7]-[C:5](=[O;D1;H0:4])-[O;D1;H1:6]
52.2
[{"value": 52.0, "product": "C(C)(=O)OC1=C(C(=O)O)C=C(C=C1)NC(=O)OC(C)(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 52.2, "product": "C(C)(=O)OC1=C(C(=O)O)C=C(C=C1)NC(=O)OC(C)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
4
HOUR
To a solution of 5-tert-butoxycarbonylamino-2-hydroxybenzoic acid (1.02 g, 4.02 mmole) in DMF (20.0 ml) was added with acetyl chloride (39 mg, 4.83 mmole) and potassium carbonate (555 mg, 4.02 mmole). The reaction mixture was stirred for 4 hr at room temperature. After the reaction mixture was concentrated, the residue...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Aromatic alcohol
Ester
null
null
c1ccccc1
HCl
CN(C)C=O
null
4
CC(=O)Cl.CC(C)(C)OC(=O)Nc1ccc(O)c(C(=O)O)c1>CN(C)C=O>CC(=O)Oc1ccc(NC(=O)OC(C)(C)C)cc1C(=O)O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f99c4245f5024eafbed92d5ba276e740
CC(=O)Oc1ccc(NC(=O)OC(C)(C)C)cc1C(=O)O>>CC(=O)Oc1ccc(N)cc1C(=O)O
C(C)(=O)OC1=C(C(=O)O)C=C(C=C1)NC(=O)OC(C)(C)C>>C(C)(=O)OC1=C(C(=O)O)C=C(C=C1)N
CC(C)(C)OC(=O)[NH:9][c:8]1[cH:7][cH:6][c:5]([O:4][C:2]([CH3:1])=[O:3])[c:11]([C:12](=[O:13])[OH:14])[cH:10]1>>[CH3:1][C:2](=[O:3])[O:4][c:5]1[cH:6][cH:7][c:8]([NH2:9])[cH:10][c:11]1[C:12](=[O:13])[OH:14]
CC(=O)Oc1ccc(NC(=O)OC(C)(C)C)cc1C(=O)O
CC(=O)Oc1ccc(N)cc1C(=O)O
null
null
C(=O)(C(F)(F)F)O.C(Cl)Cl
Reduction
Hydrogenolysis of amides/imides/carbamates
3c33dd2a2d355ee5ba0287367e209aa147a39aa00607f0c95fb2bf1ade45d014
c5b5dffe7dd8beebdc1baa8b5b05300a9f7079e65dcfd42ade6f8a77ff09537d
c1ccccc1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
97.4
[{"value": 97.0, "product": "C(C)(=O)OC1=C(C(=O)O)C=C(C=C1)N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 97.4, "product": "C(C)(=O)OC1=C(C(=O)O)C=C(C=C1)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
The mixture of 2-ethanoyloxy-5-tert-butoxycarbonylaminobenzoic acid (1.01 g, 3.42 mmole) in TFA/CH2Cl2 (20.0 ml. 1:1 v/v) was stirred for 30 min at room temperature. After the reaction mixture was concentrated, the residue was dissolved in ether. The resulting residue was recrystallized from ethyl acetate/hexane to giv...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Primary amine
null
null
c1ccccc1
HO-
C(=O)(C(F)(F)F)O.C(Cl)Cl
null
0.5
CC(=O)Oc1ccc(NC(=O)OC(C)(C)C)cc1C(=O)O>C(=O)(C(F)(F)F)O.C(Cl)Cl>CC(=O)Oc1ccc(N)cc1C(=O)O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4064f24c2f454f90b18ac8aeebb5accc
CC(=O)Oc1ccc(N)cc1C(=O)O.Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr>>CC(=O)Oc1ccc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)cc1C(=O)O
C(C)(=O)OC1=C(C(=O)O)C=C(C=C1)N.FC1=C(CBr)C(=C(C(=C1F)C(F)(F)F)F)F>>C(C)(=O)OC1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F
[CH3:1][C:2](=[O:3])[O:4][c:5]1[cH:6][cH:7][c:8]([NH2:9])[cH:25][c:26]1[C:27](=[O:28])[OH:29].Br[CH2:10][c:11]1[c:12]([F:13])[c:14]([F:15])[c:16]([C:17]([F:18])([F:19])[F:20])[c:21]([F:22])[c:23]1[F:24]>>[CH3:1][C:2](=[O:3])[O:4][c:5]1[cH:6][cH:7][c:8]([NH:9][CH2:10][c:11]2[c:12]([F:13])[c:14]([F:15])[c:16]([C:17]([F:1...
CC(=O)Oc1ccc(N)cc1C(=O)O.Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr
CC(=O)Oc1ccc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)cc1C(=O)O
null
[I-].C(CCC)[N+](CCCC)(CCCC)CCCC
CN(C)C=O
Heteroatom Alkylation and Arylation
N-alkylation of primary amines with alkyl halides
fc19a1445ff204e66e51735d0191465bda3c6691fd233624a54742c9d4828411
0b1d32f56ad00f1e5bdae9390f9227bbea012fa2f8203aac34726b8a6761cc7c
c1ccc(CNc2ccccc2)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[NH2;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[c:3]:[c:2](-[CH2;D2;+0:1]-[NH;D2;+0:5]-[c:6](:[c:7]):[c:8]):[c:4]
53
[{"value": 53.0, "product": "C(C)(=O)OC1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
According to the similar procedure in Synthesis Example 1, by using 2-ethanoyloxy-5-aminobenzoic acid (0.81 g, 4.10 mmole) which was prepared from Synthesis Example (14-3), DMF (15 ml), TEA (0.1 ml), tetrabutyl ammonium iodide (5 mg), and 2,3,5,6-tetrafluoro-4-trifluoromethylbenzyl bromide (1.02 ml, 6.15 mmole), 0.92 g...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Primary amine
Secondary amine
null
null
c1ccccc1.c1ccccc1
HBr
[I-].C(CCC)[N+](CCCC)(CCCC)CCCC.CN(C)C=O
null
null
CC(=O)Oc1ccc(N)cc1C(=O)O.Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr>[I-].C(CCC)[N+](CCCC)(CCCC)CCCC.CN(C)C=O>CC(=O)Oc1ccc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)cc1C(=O)O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1bc26572ee124f468997dceac639fc1f
CCC(=O)Oc1ccc(N)cc1C(=O)O.Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr>>CCC(=O)Oc1ccc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)cc1C(=O)O
NC=1C=CC(=C(C(=O)O)C1)OC(CC)=O.FC1=C(CBr)C(=C(C(=C1F)C(F)(F)F)F)F>>C(CC)(=O)OC1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F
[CH3:1][CH2:2][C:3](=[O:4])[O:5][c:6]1[cH:7][cH:8][c:9]([NH2:10])[cH:26][c:27]1[C:28](=[O:29])[OH:30].Br[CH2:11][c:12]1[c:13]([F:14])[c:15]([F:16])[c:17]([C:18]([F:19])([F:20])[F:21])[c:22]([F:23])[c:24]1[F:25]>>[CH3:1][CH2:2][C:3](=[O:4])[O:5][c:6]1[cH:7][cH:8][c:9]([NH:10][CH2:11][c:12]2[c:13]([F:14])[c:15]([F:16])[c...
CCC(=O)Oc1ccc(N)cc1C(=O)O.Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr
CCC(=O)Oc1ccc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)cc1C(=O)O
null
[I-].C(CCC)[N+](CCCC)(CCCC)CCCC
CN(C)C=O
Heteroatom Alkylation and Arylation
N-alkylation of primary amines with alkyl halides
fc19a1445ff204e66e51735d0191465bda3c6691fd233624a54742c9d4828411
0b1d32f56ad00f1e5bdae9390f9227bbea012fa2f8203aac34726b8a6761cc7c
c1ccc(CNc2ccccc2)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[NH2;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[c:3]:[c:2](-[CH2;D2;+0:1]-[NH;D2;+0:5]-[c:6](:[c:7]):[c:8]):[c:4]
51
[{"value": 51.0, "product": "C(CC)(=O)OC1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
According to the similar procedure in Synthesis Example 14-4, by using 5-amino-2-propanoyloxybenzoic acid (0.32 g, 1.53 mmole) which was prepared from Synthesis Example (15-2), DMF (10 ml), TEA (0.05 ml), tetrabutyl ammonium iodide (3 mg), and 2,3,5,6-tetrafluoro-4-trifluoromethylbenzyl bromide (0.38 ml, 2.30 mmole), 0...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Primary amine
Secondary amine
null
null
c1ccccc1.c1ccccc1
HBr
[I-].C(CCC)[N+](CCCC)(CCCC)CCCC.CN(C)C=O
null
null
CCC(=O)Oc1ccc(N)cc1C(=O)O.Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr>[I-].C(CCC)[N+](CCCC)(CCCC)CCCC.CN(C)C=O>CCC(=O)Oc1ccc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)cc1C(=O)O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ae901311a46d4e2eb7b0e3a82f66843e
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(OC(=O)C2CCCCC2)c(C(=O)O)c1>>O=C(O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1OC(=O)C1CCCCC1
NC=1C=CC(=C(C(=O)O)C1)OC(=O)C1CCCCC1.FC1=C(CBr)C(=C(C(=C1F)C(F)(F)F)F)F>>C1(CCCCC1)C(=O)OC1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F
Br[CH2:8][c:9]1[c:10]([F:11])[c:12]([F:13])[c:14]([C:15]([F:16])([F:17])[F:18])[c:19]([F:20])[c:21]1[F:22].[O:1]=[C:2]([OH:3])[c:4]1[cH:5][c:6]([NH2:7])[cH:23][cH:24][c:25]1[O:26][C:27](=[O:28])[CH:29]1[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]1>>[O:1]=[C:2]([OH:3])[c:4]1[cH:5][c:6]([NH:7][CH2:8][c:9]2[c:10]([F:11])[c:12...
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(OC(=O)C2CCCCC2)c(C(=O)O)c1
O=C(O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1OC(=O)C1CCCCC1
null
[I-].C(CCC)[N+](CCCC)(CCCC)CCCC
CN(C)C=O
Heteroatom Alkylation and Arylation
N-alkylation of primary amines with alkyl halides
fc19a1445ff204e66e51735d0191465bda3c6691fd233624a54742c9d4828411
0b1d32f56ad00f1e5bdae9390f9227bbea012fa2f8203aac34726b8a6761cc7c
O=C(Oc1ccc(NCc2ccccc2)cc1)C1CCCCC1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[NH2;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[c:3]:[c:2](-[CH2;D2;+0:1]-[NH;D2;+0:5]-[c:6](:[c:7]):[c:8]):[c:4]
49
[{"value": 49.0, "product": "C1(CCCCC1)C(=O)OC1=C(C(=O)O)C=C(C=C1)NCC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
According to the similar procedure in Synthesis Example (14-4), by using 5-amino-2-cyclohexanecarbonyloxybenzoic acid (1.03 g, 3.95 mmole) which was prepared from Synthesis Example (16-2), DMF (15 ml), TEA (0.10 ml), tetrabutyl ammonium iodide (10 mg), and 2,3,5,6-tetrafluoro-4-trifluoromethylbenzyl bromide (1.01 ml, 5...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Primary amine
Secondary amine
null
null
c1ccccc1.c1ccccc1.C1CCCCC1
HBr
[I-].C(CCC)[N+](CCCC)(CCCC)CCCC.CN(C)C=O
null
null
Fc1c(F)c(C(F)(F)F)c(F)c(F)c1CBr.Nc1ccc(OC(=O)C2CCCCC2)c(C(=O)O)c1>[I-].C(CCC)[N+](CCCC)(CCCC)CCCC.CN(C)C=O>O=C(O)c1cc(NCc2c(F)c(F)c(C(F)(F)F)c(F)c2F)ccc1OC(=O)C1CCCCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a2f5b3af7a1a425d85bfd0a6f9b274fa
CC(C)(C)OC(=O)Nc1cccnc1.O=C=Nc1ccc(Cl)cc1>>CC(C)(C)OC(=O)Nc1cnccc1C(=O)Nc1ccc(Cl)cc1
C(C)(C)(C)OC(=O)NC=1C=NC=CC1.[Li]C(C)(C)C.ClC1=CC=C(C=C1)N=C=O>>C(C)(C)(C)OC(=O)NC=1C=NC=CC1C(=O)NC1=CC=C(C=C1)Cl
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][c:9]1[cH:10][n:11][cH:12][cH:13][cH:14]1.[C:15](=[O:16])=[N:17][c:18]1[cH:19][cH:20][c:21]([Cl:22])[cH:23][cH:24]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][c:9]1[cH:10][n:11][cH:12][cH:13][c:14]1[C:15](=[O:16])[NH:17][c:18]1[cH:19][cH:20][c:21]([Cl:2...
CC(C)(C)OC(=O)Nc1cccnc1.O=C=Nc1ccc(Cl)cc1
CC(C)(C)OC(=O)Nc1cnccc1C(=O)Nc1ccc(Cl)cc1
null
null
C1CCOC1
Acylation
OtherReaction
83e204f94d06c21a57e066d9b0f22fdad61493b015559d3b3ec187461ef75bb8
3347203d95f451dc113645420a6f5b484c71b9ef5d3ed902199ccd8a70632b86
O=C(Nc1ccccc1)c1ccncc1
[C;D1;H3:1]-[C:2](-[C;D1;H3:3])(-[C;D1;H3:4])-[#8:5]-[C:6](=[O;D1;H0:7])-[#7:8]-[c:9]1:[c:10]:[#7;a:11]:[c:12]:[c:13]:[cH;D2;+0:14]:1.[O;D1;H0:15]=[C;H0;D2;+0:16]=[N;H0;D2;+0:17]-[c:18](:[c:19]):[c:20]>>[C;D1;H3:1]-[C:2](-[C;D1;H3:3])(-[C;D1;H3:4])-[#8:5]-[C:6](=[O;D1;H0:7])-[#7:8]-[c:9]1:[c:10]:[#7;a:11]:[c:12]:[c:13]...
36
[{"value": 36.0, "product": "C(C)(C)(C)OC(=O)NC=1C=NC=CC1C(=O)NC1=CC=C(C=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 35.8, "product": "C(C)(C)(C)OC(=O)NC=1C=NC=CC1C(=O)NC1=CC=C(C=C1)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-30
CELSIUS
1
HOUR
The 3-tert-butoxycarbonylaminopyridine (2.0035 g, 10.32 mmol) was dissolved in THF (100 mL). The solution was cooled to −30° C. in a dry ice/acetonitrile bath, then t-BuLi (13 mL, 22.1 mmol) was added dropwise. After 1 h, 4-chlorophenyl isocyanate (1.911 g, 12.44 mmol) was added. The reaction mixture was warmed to 0° C...
10.6084/m9.figshare.5104873.v1
null
Isocyanate
Secondary amide
c1ccncc1
c1ccncc1
c1ccncc1.c1ccccc1
null
C1CCOC1
-30
1
CC(C)(C)OC(=O)Nc1cccnc1.O=C=Nc1ccc(Cl)cc1>C1CCOC1>CC(C)(C)OC(=O)Nc1cnccc1C(=O)Nc1ccc(Cl)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3c0ec90aa0e64da095384d499776ad82
CC(C)(C)OC(=O)Nc1cnccc1C(=O)Nc1ccc(Cl)cc1>>Nc1cnccc1C(=O)Nc1ccc(Cl)cc1
C(C)(C)(C)OC(=O)NC=1C=NC=CC1C(=O)NC1=CC=C(C=C1)Cl.FC(C(=O)O)(F)F>>NC=1C=NC=CC1C(=O)NC1=CC=C(C=C1)Cl
CC(C)(C)OC(=O)[NH:1][c:2]1[cH:3][n:4][cH:5][cH:6][c:7]1[C:8](=[O:9])[NH:10][c:11]1[cH:12][cH:13][c:14]([Cl:15])[cH:16][cH:17]1>>[NH2:1][c:2]1[cH:3][n:4][cH:5][cH:6][c:7]1[C:8](=[O:9])[NH:10][c:11]1[cH:12][cH:13][c:14]([Cl:15])[cH:16][cH:17]1
CC(C)(C)OC(=O)Nc1cnccc1C(=O)Nc1ccc(Cl)cc1
Nc1cnccc1C(=O)Nc1ccc(Cl)cc1
null
null
null
Reduction
Hydrogenolysis of amides/imides/carbamates
3c33dd2a2d355ee5ba0287367e209aa147a39aa00607f0c95fb2bf1ade45d014
c5b5dffe7dd8beebdc1baa8b5b05300a9f7079e65dcfd42ade6f8a77ff09537d
O=C(Nc1ccccc1)c1ccncc1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[c:2](:[c:3]:[#7;a:4]:[c:5]):[c:6]-[C:7](-[#7:8])=[O;D1;H0:9]>>[#7:8]-[C:7](=[O;D1;H0:9])-[c:6]:[c:2](-[NH2;D1;+0:1]):[c:3]:[#7;a:4]:[c:5]
93.2
[{"value": 93.0, "product": "NC=1C=NC=CC1C(=O)NC1=CC=C(C=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 93.2, "product": "NC=1C=NC=CC1C(=O)NC1=CC=C(C=C1)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
10
MINUTE
To 3-(N-tert-butoxycarbonylamino)-N-(4-chlorophenyl)-pyridine-4-carboxamide (552 mg, 1.59 mmol) was added trifluoroacetic acid (3 mL, 38.95 mmol). After stirring for 10 min, the reaction mixture was concentrated, diluted with CH2Cl2, washed with satd Na2CO3, dried (Na2SO4) and concentrated to give the title compound (3...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Primary amine
null
null
c1ccncc1.c1ccccc1
HO-
null
null
0.166667
CC(C)(C)OC(=O)Nc1cnccc1C(=O)Nc1ccc(Cl)cc1>>Nc1cnccc1C(=O)Nc1ccc(Cl)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-72635546d05941bc89539332989fdc4d
C[Si](C)(C)C=[N+]=[N-].O=C(O)c1ccc(F)cc1O>>COC(=O)c1ccc(F)cc1O
C[Si](C)(C)C=[N+]=[N-].FC1=CC(=C(C(=O)O)C=C1)O.CCCCCC.C[Si](C)(C)C=[N+]=[N-]>>FC1=CC(=C(C(=O)OC)C=C1)O
C[Si](C)(C)[CH:1]=[N+]=[N-].[OH:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([F:9])[cH:10][c:11]1[OH:12]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([F:9])[cH:10][c:11]1[OH:12]
C[Si](C)(C)C=[N+]=[N-].O=C(O)c1ccc(F)cc1O
COC(=O)c1ccc(F)cc1O
null
null
C1=CC=CC=C1.CO
Heteroatom Alkylation and Arylation
O-alkylation of carboxylic acids with diazo compounds
39589be0e9a30df66714fe618d22a8ac0fb24901dbf2ead1ab33e31556c7ac64
8b539baf7aeb5ab868833e33306bad77200a853d562904197e13de2e27e229d7
c1ccccc1
C-[Si](-C)(-C)-[CH;D2;+0:1]=[N+]=[N-].[O;D1;H0:2]=[C:3](-[OH;D1;+0:4])-[c:5]>>[CH3;D1;+0:1]-[O;H0;D2;+0:4]-[C:3](=[O;D1;H0:2])-[c:5]
98
[{"value": 98.0, "product": "FC1=CC(=C(C(=O)OC)C=C1)O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
A solution of 4-fluoro-2-hydroxybenzoic acid (9.8 g, 62.3 mmol) in benzene (100 mL) and MeOH (20 mL) was cooled in an ice bath and a 2 M hexane solution of (trimethyl-silyl)diazomethane (50 mL) was added dropwise. The reaction was stirred overnight at ambient temperature, diluted with benzene (348 mL) and MeOH (39 mL),...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Diazo.Silyl protective group
Ester
null
null
c1ccccc1
Other
C1=CC=CC=C1.CO
null
8
C[Si](C)(C)C=[N+]=[N-].O=C(O)c1ccc(F)cc1O>C1=CC=CC=C1.CO>COC(=O)c1ccc(F)cc1O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5b54b93e44bc459fb114f8396288f7b7
CC(C)(C)OC(=O)N1CCC(O)CC1.COC(=O)c1ccc(F)cc1O>>COC(=O)c1ccc(F)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
N(=NC(=O)OCC)C(=O)OCC.FC1=CC(=C(C(=O)OC)C=C1)O.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C(C)(C)(C)OC(=O)N1CCC(CC1)O>>C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)OC)C=CC(=C1)F
O[CH:13]1[CH2:14][CH2:15][N:16]([C:17](=[O:18])[O:19][C:20]([CH3:21])([CH3:22])[CH3:23])[CH2:24][CH2:25]1.[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([F:9])[cH:10][c:11]1[OH:12]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([F:9])[cH:10][c:11]1[O:12][CH:13]1[CH2:14][CH2:15][N:16]([C:17](=[O:18])[O:19][C:20]([C...
CC(C)(C)OC(=O)N1CCC(O)CC1.COC(=O)c1ccc(F)cc1O
COC(=O)c1ccc(F)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
null
null
C1=CC=CC=C1.C(Cl)Cl
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
a9e936b0e9135225700edbab1c7696738b7f1f0756494b6ceeeda63b184d572f
776ba735002e33225fbc578943016110c2c43efefd97bfeea4ec3cc2e2e1532f
c1ccc(OC2CCNCC2)cc1
O-[CH;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1.[#8:7]-[C:8](=[O;D1;H0:9])-[c:10]:[c:11](-[OH;D1;+0:12]):[c:13]>>[#8:7]-[C:8](=[O;D1;H0:9])-[c:10]:[c:11](-[O;H0;D2;+0:12]-[CH;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1):[c:13]
61
[{"value": 61.0, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)OC)C=CC(=C1)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 60.8, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)OC)C=CC(=C1)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
null
null
A mixture of methyl 4-fluoro-2-hydroxybenzoate (5.1 g, 30 mmol), triphenylphosphine (9.5 g, 36 mmol), 1-tert-butoxycarbonyl-4-hydroxypiperidine (6 g, 30 mmol), and benzene (10 mL) was heated until all solids dissolved. The solution was cooled to 0° C., then sonicated while adding diethyl azodicarboxylate (6.3 g, 36 mmo...
10.6084/m9.figshare.5104873.v1
null
Secondary alcohol.Aromatic alcohol
Ether
C1CC[NH]CC1
C1CC[NH]CC1
c1ccccc1.C1CC[NH]CC1
HO-
C1=CC=CC=C1.C(Cl)Cl
0
null
CC(C)(C)OC(=O)N1CCC(O)CC1.COC(=O)c1ccc(F)cc1O>C1=CC=CC=C1.C(Cl)Cl>COC(=O)c1ccc(F)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-474ff65ba61c420db473efdf7d92bd68
C1CCNC1.COC(=O)c1ccc(F)cc1OC1CCN(C(=O)OC(C)(C)C)CC1>>COC(=O)c1ccc(N2CCCC2)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)OC)C=CC(=C1)F.N1CCCC1>>C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)OC)C=CC(=C1)N1CCCC1
[NH:9]1[CH2:10][CH2:11][CH2:12][CH2:13]1.F[c:8]1[cH:7][cH:6][c:5]([C:3]([O:2][CH3:1])=[O:4])[c:15]([O:16][CH:17]2[CH2:18][CH2:19][N:20]([C:21](=[O:22])[O:23][C:24]([CH3:25])([CH3:26])[CH3:27])[CH2:28][CH2:29]2)[cH:14]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([N:9]2[CH2:10][CH2:11][CH2:12][CH2:13]2)[cH:14][c:1...
C1CCNC1.COC(=O)c1ccc(F)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
COC(=O)c1ccc(N2CCCC2)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
null
null
null
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation secondary amine
389dbc6c760ba22d5b089335787069e4da1dc4ed4889d745a0e1de1824c34c09
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1cc(OC2CCNCC2)cc(N2CCCC2)c1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C:6]1-[C:7]-[C:8]-[C:9]-[NH;D2;+0:10]-1>>[c:3]:[c:2]:[c;H0;D3;+0:1](-[N;H0;D3;+0:10]1-[C:6]-[C:7]-[C:8]-[C:9]-1):[c:4]:[c:5]
282.8
[{"value": 100.0, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)OC)C=CC(=C1)N1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 282.8, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)OC)C=CC(=C1)N1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
3
HOUR
The methyl 2-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-fluorobenzoate (7.99 mmol, 22.6 mmol) was diluted with pyrrolidine (18 mL, 215.6 mmol). The resulting mixture was heated to 80° C. After 3 h, the reaction mixture was cooled to room temperature and quenched with water (50 mL). The mixture was extracted with dichlo...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CCNC1.c1ccccc1
c1ccccc1.C1CC[NH]C1
c1ccccc1.C1CC[NH]C1.C1CC[NH]CC1
HF
null
80
3
C1CCNC1.COC(=O)c1ccc(F)cc1OC1CCN(C(=O)OC(C)(C)C)CC1>>COC(=O)c1ccc(N2CCCC2)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c19dc6be78b24ac5b520a14c933ce49f
COC(=O)c1ccc(N2CCCC2)cc1OC1CCN(C(=O)OC(C)(C)C)CC1>>CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2C(=O)O)CC1
C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)OC)C=CC(=C1)N1CCCC1.[Li+].[OH-].CO>>C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)O)C=CC(=C1)N1CCCC1
C[O:26][C:24]([c:23]1[c:13]([O:12][CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:28][CH2:27]2)[cH:14][c:15]([N:16]2[CH2:17][CH2:18][CH2:19][CH2:20]2)[cH:21][cH:22]1)=[O:25]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH:11]([O:12][c:13]2[cH:14][c:15]([N:16]...
COC(=O)c1ccc(N2CCCC2)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2C(=O)O)CC1
null
null
C1CCOC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1cc(OC2CCNCC2)cc(N2CCCC2)c1
C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]>>[O;D1;H0:3]=[C:2](-[OH;D1;+0:1])-[c:4]
78.2
[{"value": 78.0, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)O)C=CC(=C1)N1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 78.2, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)O)C=CC(=C1)N1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
null
null
A mixture of methyl 2-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-(pyrrolidin-1-yl)benzoate (9.133 g, 22.6 mmol), 1 M LiOH (40 mL, 40 mmol), MeOH (30 mL) and THF (90 mL) was heated at 60° C. for 14 h. The reaction mixture was concentrated to one-third of its initial volume, diluted with EtOAc (700 mL), and washed with s...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CC[NH]CC1.c1ccccc1.C1CC[NH]C1
Other
C1CCOC1
60
null
COC(=O)c1ccc(N2CCCC2)cc1OC1CCN(C(=O)OC(C)(C)C)CC1>C1CCOC1>CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2C(=O)O)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d389d159301e4655a135a97230471e10
COC(=O)c1ccc(F)cc1OC1CCN(C(=O)OC(C)(C)C)CC1>>CC(C)(C)OC(=O)N1CCC(Oc2cc(F)ccc2C(=O)O)CC1
C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)OC)C=CC(=C1)F.[Li+].[OH-].CO.C1CCOC1>>C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)O)C=CC(=C1)F
C[O:22][C:20]([c:19]1[c:13]([O:12][CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:24][CH2:23]2)[cH:14][c:15]([F:16])[cH:17][cH:18]1)=[O:21]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH:11]([O:12][c:13]2[cH:14][c:15]([F:16])[cH:17][cH:18][c:19]2[C:20](=[O:2...
COC(=O)c1ccc(F)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
CC(C)(C)OC(=O)N1CCC(Oc2cc(F)ccc2C(=O)O)CC1
null
null
CCOC(=O)C
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(OC2CCNCC2)cc1
C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]>>[O;D1;H0:3]=[C:2](-[OH;D1;+0:1])-[c:4]
76.1
[{"value": 76.0, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)O)C=CC(=C1)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 76.1, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)O)C=CC(=C1)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
A mixture of methyl 2-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-fluorobenzoate (3.05 g, 8.64 mmol), 1 M aq LiOH (15 mL, 15 mmol), MeOH (15 mL), and THF (45 mL) was stirred overnight. The reaction mixture was diluted with EtOAc, washed with satd citric acid, dried over MgSO4, concentrated, and triturated with ether to ...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CC[NH]CC1.c1ccccc1
Other
CCOC(=O)C
null
8
COC(=O)c1ccc(F)cc1OC1CCN(C(=O)OC(C)(C)C)CC1>CCOC(=O)C>CC(C)(C)OC(=O)N1CCC(Oc2cc(F)ccc2C(=O)O)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-503ed7f5676548619595cdfb9337a1fe
CC(C)(C)OC(=O)N1CCC(O)CC1.COC(=O)c1ccc(C(C)(C)C)cc1O>>COC(=O)c1ccc(C(C)(C)C)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
N(=NC(=O)OC(C)C)C(=O)OC(C)C.C(C)(C)(C)C1=CC(=C(C(=O)OC)C=C1)O.C(=O)(OC(C)(C)C)N1CCC(CC1)O.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1>>C(C)(C)(C)C1=CC(=C(C(=O)OC)C=C1)OC1CCN(CC1)C(=O)OC(C)(C)C
O[CH:16]1[CH2:17][CH2:18][N:19]([C:20](=[O:21])[O:22][C:23]([CH3:24])([CH3:25])[CH3:26])[CH2:27][CH2:28]1.[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([C:9]([CH3:10])([CH3:11])[CH3:12])[cH:13][c:14]1[OH:15]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([C:9]([CH3:10])([CH3:11])[CH3:12])[cH:13][c:14]1[O:15][CH:1...
CC(C)(C)OC(=O)N1CCC(O)CC1.COC(=O)c1ccc(C(C)(C)C)cc1O
COC(=O)c1ccc(C(C)(C)C)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
a9e936b0e9135225700edbab1c7696738b7f1f0756494b6ceeeda63b184d572f
776ba735002e33225fbc578943016110c2c43efefd97bfeea4ec3cc2e2e1532f
c1ccc(OC2CCNCC2)cc1
O-[CH;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1.[#8:7]-[C:8](=[O;D1;H0:9])-[c:10]:[c:11](-[OH;D1;+0:12]):[c:13]>>[#8:7]-[C:8](=[O;D1;H0:9])-[c:10]:[c:11](-[O;H0;D2;+0:12]-[CH;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1):[c:13]
null
[]
null
null
72
HOUR
To a stirring solution of methyl 4-tert-butyl-2-hydroxybenzoate (9.45 g, 45.4 mmol), 1-Boc-piperidin-4-ol (9.6 g, 47.7 mmol) and triphenylphosphine (12.5 g, 47.7 mmol) in THF (125 mL) was added, dropwise via an addition funnel, a solution of diisopropyl azodicarboxylate (9.4 mL, 47.7 mmol) in THF (25 mL). After 72 h, t...
10.6084/m9.figshare.5104873.v1
null
Secondary alcohol.Aromatic alcohol
Ether
C1CC[NH]CC1
C1CC[NH]CC1
c1ccccc1.C1CC[NH]CC1
HO-
C1CCOC1
null
72
CC(C)(C)OC(=O)N1CCC(O)CC1.COC(=O)c1ccc(C(C)(C)C)cc1O>C1CCOC1>COC(=O)c1ccc(C(C)(C)C)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f322c29aeb1e485caf31e657dd35d2b8
COC(=O)c1ccc(C(C)(C)C)cc1OC1CCN(C(=O)OC(C)(C)C)CC1>>CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)O)CC1
C(C)(C)(C)C1=CC(=C(C(=O)OC)C=C1)OC1CCN(CC1)C(=O)OC(C)(C)C.O[Li].O>>C(C)(C)(C)C1=CC(=C(C(=O)O)C=C1)OC1CCN(CC1)C(=O)OC(C)(C)C
C[O:25][C:23]([c:22]1[c:13]([O:12][CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:27][CH2:26]2)[cH:14][c:15]([C:16]([CH3:17])([CH3:18])[CH3:19])[cH:20][cH:21]1)=[O:24]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH:11]([O:12][c:13]2[cH:14][c:15]([C:16]([CH3:...
COC(=O)c1ccc(C(C)(C)C)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)O)CC1
null
null
O1CCOCC1.O
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(OC2CCNCC2)cc1
C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]>>[O;D1;H0:3]=[C:2](-[OH;D1;+0:1])-[c:4]
91
[{"value": 91.0, "product": "C(C)(C)(C)C1=CC(=C(C(=O)O)C=C1)OC1CCN(CC1)C(=O)OC(C)(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 90.7, "product": "C(C)(C)(C)C1=CC(=C(C(=O)O)C=C1)OC1CCN(CC1)C(=O)OC(C)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a stirring solution of methyl 4-(tert-butyl)-2-(1-Boc-piperidin-4-yloxy)benzoate (12.9 g, 33 mmol) in p-dioxane (150 mL) was added a solution of LiOH hydrate (2.8 g, 66 mmol) in water (75 mL). The next morning, the solvent was removed in vacuo, and the residue was diluted with water (200 mL) and washed with diethyl ...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CC[NH]CC1.c1ccccc1
Other
O1CCOCC1.O
null
null
COC(=O)c1ccc(C(C)(C)C)cc1OC1CCN(C(=O)OC(C)(C)C)CC1>O1CCOCC1.O>CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)O)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2824e47e2c2d4ebf8986ba5d92c2c82d
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)O)CC1.Nc1cccnc1C(=O)Nc1ccc(Cl)cn1.O=C([O-])C(F)(F)F>>CC(C)(C)c1ccc(C(=O)Nc2cccnc2C(=O)Nc2ccc(Cl)cn2)c(OC2CCNCC2)c1.O=C(O)C(F)(F)F
NC=1C(=NC=CC1)C(=O)NC1=NC=C(C=C1)Cl.C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)O)C=CC(=C1)C(C)(C)C.FC(C(=O)[O-])(F)F>>FC(C(=O)O)(F)F.C(C)(C)(C)C1=CC(=C(C(=O)NC=2C(=NC=CC2)C(=O)NC2=NC=C(C=C2)Cl)C=C1)OC1CCNCC1
CC(C)(C)OC(=O)[N:33]1[CH2:32][CH2:31][CH:30]([O:29][c:28]2[c:8]([C:9](O)=[O:10])[cH:7][cH:6][c:5]([C:2]([CH3:1])([CH3:3])[CH3:4])[cH:36]2)[CH2:35][CH2:34]1.[NH2:11][c:12]1[cH:13][cH:14][cH:15][n:16][c:17]1[C:18](=[O:19])[NH:20][c:21]1[cH:22][cH:23][c:24]([Cl:25])[cH:26][n:27]1.[O:37]=[C:38]([O-:39])[C:40]([F:41])([F:42...
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)O)CC1.Nc1cccnc1C(=O)Nc1ccc(Cl)cn1.O=C([O-])C(F)(F)F
CC(C)(C)c1ccc(C(=O)Nc2cccnc2C(=O)Nc2ccc(Cl)cn2)c(OC2CCNCC2)c1.O=C(O)C(F)(F)F
null
null
null
Protection
OtherReaction
7b8bd0a5903e8e7c9e6eb0e6d81e832fb78e2f9a7f8a1a8ebe542a80dfd09347
56cbaae9039b7a3d35974b4340a6737b25f33de7957a48106ebbad7a8d9a3713
O=C(Nc1cccnc1C(=O)Nc1ccccn1)c1ccccc1OC1CCNCC1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1](-[C:2]-[C:3])-[C:4]-[C:5].O-[C;H0;D3;+0:6](=[O;D1;H0:7])-[c:8](:[c:9]):[c:10].[#7:11]-[C:12](=[O;D1;H0:13])-[c:14](:[#7;a:15]:[c:16]):[c:17](-[NH2;D1;+0:18]):[c:19].[F;D1;H0:20]-[C:21](-[F;D1;H0:22])(-[F;D1;H0:23])-[C:24](-[O-;H0;D1:25])=[O;D1;H0:26]>>[#7:11]-[C:12](=[O;D1;H0:13])-[c:...
30
[{"value": 30.0, "product": "FC(C(=O)O)(F)F.C(C)(C)(C)C1=CC(=C(C(=O)NC=2C(=NC=CC2)C(=O)NC2=NC=C(C=C2)Cl)C=C1)OC1CCNCC1", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Using methods substantially equivalent to those described in Example 1-I, 3-amino-N-(5-chloropyridin-2-yl)-pyridine-2-carboxamide (626 mg, 2.52 mmol) and 2-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-tert-butylbenzoic acid (500 mg, 1.47 mmol) yielded, after deprotection of the coupled product using methods substantially...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Carboxylic acid.Ether.Primary amine.Boc
Carboxylic acid.Secondary amide.Secondary amine
C1CC[NH]CC1
C1CCNCC1
c1ccccc1.c1ccncc1.c1ccncc1.C1CCNCC1
HO-
null
null
null
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)O)CC1.Nc1cccnc1C(=O)Nc1ccc(Cl)cn1.O=C([O-])C(F)(F)F>>CC(C)(C)c1ccc(C(=O)Nc2cccnc2C(=O)Nc2ccc(Cl)cn2)c(OC2CCNCC2)c1.O=C(O)C(F)(F)F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5725c0e56974409fad22d836a0ede21a
CO.COCOc1cc(C(C)(C)C)ccc1C(=O)O>>COC(=O)c1ccc(C(C)(C)C)cc1O
C(C)(C)(C)C1=CC(=C(C(=O)O)C=C1)OCOC.CO>>C(C)(C)(C)C1=CC(=C(C(=O)OC)C=C1)O
O[CH3:1].COC[O:15][c:14]1[c:5]([C:3]([OH:2])=[O:4])[cH:6][cH:7][c:8]([C:9]([CH3:10])([CH3:11])[CH3:12])[cH:13]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([C:9]([CH3:10])([CH3:11])[CH3:12])[cH:13][c:14]1[OH:15]
CO.COCOc1cc(C(C)(C)C)ccc1C(=O)O
COC(=O)c1ccc(C(C)(C)C)cc1O
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
d91c443ba57fb40e0967883daa0187a51b2b8803be256f291442bd62ce559ed9
a908e90609f639256990fb4c36be9ac4315f79d646aca954876e9a637ca9dd82
c1ccccc1
C-O-C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]-[C:5](=[O;D1;H0:6])-[OH;D1;+0:7].O-[CH3;D1;+0:8]>>[CH3;D1;+0:8]-[O;H0;D2;+0:7]-[C:5](=[O;D1;H0:6])-[c:4]:[c:2](-[OH;D1;+0:1]):[c:3]
null
[]
null
null
null
null
A solution of 4-tert-butyl-2-(methoxymethoxy)benzoic acid (61.80 g, 259 mmol) and MeOH (865 mL) was cooled in an ice bath. Gaseous HCl was sparged through the cold fluid for 30 min to saturate it, and the solution was then heated to reflux. A Soxhlet extractor containing 3 Å molecular sieves was used to absorb the wate...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Ether.Ether.Methanol
Ester.Aromatic alcohol
null
null
c1ccccc1
HO-
null
null
null
CO.COCOc1cc(C(C)(C)C)ccc1C(=O)O>>COC(=O)c1ccc(C(C)(C)C)cc1O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-47b76ad718ce4b32b774f444c4c5d7a8
CC(C)c1cccc(O)c1.COCCl>>COCOc1cccc(C(C)C)c1
C(C)(C)C=1C=C(C=CC1)O.C(C)(C)N(CC)C(C)C.COCCl>>C(C)(C)C1=CC(=CC=C1)OCOC
[OH:4][c:5]1[cH:6][cH:7][cH:8][c:9]([CH:10]([CH3:11])[CH3:12])[cH:13]1.Cl[CH2:3][O:2][CH3:1]>>[CH3:1][O:2][CH2:3][O:4][c:5]1[cH:6][cH:7][cH:8][c:9]([CH:10]([CH3:11])[CH3:12])[cH:13]1
CC(C)c1cccc(O)c1.COCCl
COCOc1cccc(C(C)C)c1
null
null
O.C(Cl)Cl
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
6e90ffbf0683e1a3ee55c5e3ea453aefc5ddd369c0150ed0150f9546d7e47f4f
efd670663709b79afcad1306da9f69b33a0147cfa3639ca4c0b54b35ef4b1852
c1ccccc1
Cl-[CH2;D2;+0:1]-[#8:2]-[C;D1;H3:3].[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[C;D1;H3:3]-[#8:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]
56
[{"value": 56.0, "product": "C(C)(C)C1=CC(=CC=C1)OCOC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 55.5, "product": "C(C)(C)C1=CC(=CC=C1)OCOC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
Into methylene chloride (300 mL) was dissolved 3-isopropylphenol (27.24 g, 200 mmol). After cooling the solution in an ice bath, diisopropylethyl amine (69.7 mL, 400 mmol) was added in one portion, followed by the dropwise addition of chloromethyl methyl ether (18.9 mL, 236 mmol) in methylene chloride (50 mL). The reac...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ether.Aromatic alcohol
Ether.Ether
null
null
c1ccccc1
HCl
O.C(Cl)Cl
null
16
CC(C)c1cccc(O)c1.COCCl>O.C(Cl)Cl>COCOc1cccc(C(C)C)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-34d6ef1d399e470fa61f10610c2eca38
COCOc1cc(C(C)C)ccc1C(=O)O>>COC(=O)c1ccc(C(C)C)cc1O
C[Si](C)(C)C=[N+]=[N-].C(C)(=O)Cl.C(C)(C)C1=CC(=C(C(=O)O)C=C1)OCOC.Cl>>C(C)(C)C1=CC(=C(C(=O)OC)C=C1)O
C(O[CH3:1])[O:14][c:13]1[c:5]([C:3]([OH:2])=[O:4])[cH:6][cH:7][c:8]([CH:9]([CH3:10])[CH3:11])[cH:12]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([CH:9]([CH3:10])[CH3:11])[cH:12][c:13]1[OH:14]
COCOc1cc(C(C)C)ccc1C(=O)O
COC(=O)c1ccc(C(C)C)cc1O
null
null
CCCCCC.C(Cl)Cl.CO
Miscellaneous
OtherReaction
63e23a9fe2462a14c98b1466cfbe5f3f59528d6fd75acfa2a84c440daa67b1ed
07b207b90c7119940291c3edd7051bccfd65e305571c0c76ed1431969e2388d0
c1ccccc1
[CH3;D1;+0:1]-O-C-[O;H0;D2;+0:2]-[c:3](:[c:4]):[c:5]-[C:6](=[O;D1;H0:7])-[OH;D1;+0:8]>>[CH3;D1;+0:1]-[O;H0;D2;+0:8]-[C:6](=[O;D1;H0:7])-[c:5]:[c:3](-[OH;D1;+0:2]):[c:4]
null
[]
null
null
2
HOUR
The 4-isopropyl-2-methoxymethoxybenzoic acid (5.3 g, 23.6 mmol) was dissolved in methylene chloride (75 mL) and MeOH (75 mL). Acetyl chloride (1 mL) was added to generate HCl. The reaction mixture was stirred for 2 h. The reaction was washed with water (2×150 mL), dried (MgSO4), and concentrated under vacuum. The crude...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Ether.Ether
Ester.Aromatic alcohol
null
null
c1ccccc1
HO-
CCCCCC.C(Cl)Cl.CO
null
2
COCOc1cc(C(C)C)ccc1C(=O)O>CCCCCC.C(Cl)Cl.CO>COC(=O)c1ccc(C(C)C)cc1O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f3d29e400cd341f0b5639776912b6bd4
CC(C)(C)OC(=O)N1CCCC(CO)C1.COC(=O)c1ccc(C(C)C)cc1O>>COC(=O)c1ccc(C(C)C)cc1OCC1CCCN(C(=O)OC(C)(C)C)C1
OCC1CN(CCC1)C(=O)OC(C)(C)C.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C(C)(C)C1=CC(=C(C(=O)OC)C=C1)O.N(=NC(=O)OC(C)C)C(=O)OC(C)C>>C(C)(C)(C)OC(=O)N1CC(CCC1)COC1=C(C(=O)OC)C=CC(=C1)C(C)C
O[CH2:15][CH:16]1[CH2:17][CH2:18][CH2:19][N:20]([C:21](=[O:22])[O:23][C:24]([CH3:25])([CH3:26])[CH3:27])[CH2:28]1.[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([CH:9]([CH3:10])[CH3:11])[cH:12][c:13]1[OH:14]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([CH:9]([CH3:10])[CH3:11])[cH:12][c:13]1[O:14][CH2:15][CH:16]...
CC(C)(C)OC(=O)N1CCCC(CO)C1.COC(=O)c1ccc(C(C)C)cc1O
COC(=O)c1ccc(C(C)C)cc1OCC1CCCN(C(=O)OC(C)(C)C)C1
null
null
C(Cl)Cl.C1CCOC1
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1ccc(OCC2CCCNC2)cc1
O-[CH2;D2;+0:1]-[C:2](-[C:3])-[C:4]-[#7:5].[#8:6]-[C:7](=[O;D1;H0:8])-[c:9]:[c:10](-[OH;D1;+0:11]):[c:12]>>[#7:5]-[C:4]-[C:2](-[CH2;D2;+0:1]-[O;H0;D2;+0:11]-[c:10](:[c:12]):[c:9]-[C:7](-[#8:6])=[O;D1;H0:8])-[C:3]
43
[{"value": 43.0, "product": "C(C)(C)(C)OC(=O)N1CC(CCC1)COC1=C(C(=O)OC)C=CC(=C1)C(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 37.6, "product": "C(C)(C)(C)OC(=O)N1CC(CCC1)COC1=C(C(=O)OC)C=CC(=C1)C(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
The methyl 4-isopropyl-2-hydroxybenzoate (4.4 g, 22.7 mmol) was dissolved in THF (100 mL). Then 3-(hydroxy-methyl)-1-tert-butoxycarbonylpiperidine (4.88 g, 22.7 mmol) and triphenylphosphine (7.14 g, 27.24 mmol) were added. The mixture was placed in an ice bath, and then diisopropyl azodicarboxylate (4.59 g, 22.7 mmol) ...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccccc1.C1CC[NH]CC1
HO-
C(Cl)Cl.C1CCOC1
null
16
CC(C)(C)OC(=O)N1CCCC(CO)C1.COC(=O)c1ccc(C(C)C)cc1O>C(Cl)Cl.C1CCOC1>COC(=O)c1ccc(C(C)C)cc1OCC1CCCN(C(=O)OC(C)(C)C)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-64265ceffcb246c196f3dc6e771ef307
COC(=O)c1ccc(C(C)C)cc1OCC1CCCN(C(=O)OC(C)(C)C)C1>>CC(C)c1ccc(C(=O)O)c(OCC2CCCN(C(=O)OC(C)(C)C)C2)c1
C(C)(C)C1=CC(=C(C(=O)OC)C=C1)OCC1CN(CCC1)C(=O)OC(C)(C)C.O[Li].O>>C(C)(C)(C)OC(=O)N1CC(CCC1)COC1=C(C(=O)O)C=CC(=C1)C(C)C
C[O:10][C:8]([c:7]1[cH:6][cH:5][c:4]([CH:2]([CH3:1])[CH3:3])[cH:27][c:11]1[O:12][CH2:13][CH:14]1[CH2:15][CH2:16][CH2:17][N:18]([C:19](=[O:20])[O:21][C:22]([CH3:23])([CH3:24])[CH3:25])[CH2:26]1)=[O:9]>>[CH3:1][CH:2]([CH3:3])[c:4]1[cH:5][cH:6][c:7]([C:8](=[O:9])[OH:10])[c:11]([O:12][CH2:13][CH:14]2[CH2:15][CH2:16][CH2:17...
COC(=O)c1ccc(C(C)C)cc1OCC1CCCN(C(=O)OC(C)(C)C)C1
CC(C)c1ccc(C(=O)O)c(OCC2CCCN(C(=O)OC(C)(C)C)C2)c1
null
null
O.C1CCOC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(OCC2CCCNC2)cc1
C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]>>[O;D1;H0:3]=[C:2](-[OH;D1;+0:1])-[c:4]
83.6
[{"value": 83.6, "product": "C(C)(C)(C)OC(=O)N1CC(CCC1)COC1=C(C(=O)O)C=CC(=C1)C(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
65
CELSIUS
null
null
The methyl 4-isopropyl-2-(1-tert-butoxycarbonyl-piperidin-3-ylmethoxy)benzoate (1.53 g, 3.90 mmol) was dissolved in THF (15 mL). Then LiOH.H2O (0.36 g, 8.58 mmol) in water (5 mL) was added. The mixture was heated at 65° C. for 24 h. The reaction mixture was concentrated in vacuo and then redissolved in a mixture of EtO...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.C1CC[NH]CC1
Other
O.C1CCOC1
65
null
COC(=O)c1ccc(C(C)C)cc1OCC1CCCN(C(=O)OC(C)(C)C)C1>O.C1CCOC1>CC(C)c1ccc(C(=O)O)c(OCC2CCCN(C(=O)OC(C)(C)C)C2)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-197def2531de41c1a5800dc10c81e8f3
Nc1ccc(Cl)cn1.Nc1ncccc1C(=O)O.O=C(Cl)C(=O)Cl>>Cl.Nc1ncccc1C(=O)Nc1ccc(Cl)cn1
N1=CC=CC=C1.C(C(=O)Cl)(=O)Cl.NC1=C(C(=O)O)C=CC=N1.NC1=NC=C(C=C1)Cl>>Cl.NC1=NC=CC=C1C(=O)NC1=NC=C(C=C1)Cl
[NH2:11][c:12]1[cH:13][cH:14][c:15]([Cl:16])[cH:17][n:18]1.O[C:9]([c:8]1[c:3]([NH2:2])[n:4][cH:5][cH:6][cH:7]1)=[O:10].O=C(Cl)C(=O)[Cl:1]>>[ClH:1].[NH2:2][c:3]1[n:4][cH:5][cH:6][cH:7][c:8]1[C:9](=[O:10])[NH:11][c:12]1[cH:13][cH:14][c:15]([Cl:16])[cH:17][n:18]1
Nc1ccc(Cl)cn1.Nc1ncccc1C(=O)O.O=C(Cl)C(=O)Cl
Cl.Nc1ncccc1C(=O)Nc1ccc(Cl)cn1
null
CN(C)C=O
ClCCl
Acylation
OtherReaction
1594cf5835385d20ccf6bf195a66e3c2a67922d7fd1ff78b4b8bb896d3cd2627
5ced1cc9e0cb97cfb94bb570f8e59a8d9bacd5dab9880053be8261560108ed08
O=C(Nc1ccccn1)c1cccnc1
Cl-C(=O)-C(=O)-[Cl;H0;D1;+0:1].O-[C;H0;D3;+0:2](=[O;D1;H0:3])-[c:4](:[c:5]):[c:6](-[N;D1;H2:7]):[#7;a:8]:[c:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[#7;a:13]:[c:14]>>[ClH;D0;+0:1].[N;D1;H2:7]-[c:6](:[#7;a:8]:[c:9]):[c:4](-[C;H0;D3;+0:2](=[O;D1;H0:3])-[NH;D2;+0:10]-[c:11](:[c:12]):[#7;a:13]:[c:14]):[c:5]
59.3
[{"value": 59.3, "product": "Cl.NC1=NC=CC=C1C(=O)NC1=NC=C(C=C1)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
60
MINUTE
To a stirring suspension of 2-aminonicotinic acid (26.9 g, 194 mmol) in dichloromethane (120 mL) at 0° C., was added DMF (a few drops), followed by oxalyl chloride (20 mL, 194 mmol). The cold bath was removed, and the solution was allowed to stir for 60 min at room temperature. This solution was then transferred via ca...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Acyl halide.Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccncc1.c1ccncc1
HCl
CN(C)C=O.ClCCl
null
1
Nc1ccc(Cl)cn1.Nc1ncccc1C(=O)O.O=C(Cl)C(=O)Cl>CN(C)C=O.ClCCl>Cl.Nc1ncccc1C(=O)Nc1ccc(Cl)cn1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-56a1adc8b61e4717a5028e9720267380
CC(C)(C)OC(=O)NCCCO.COC(=O)c1ccc(F)cc1O>>COC(=O)c1ccc(F)cc1OCCCNC(=O)OC(C)(C)C
FC1=CC(=C(C(=O)OC)C=C1)O.C(C)(C)(C)OC(=O)NCCCO>>C(C)(C)(C)OC(=O)NCCCOC1=C(C(=O)OC)C=CC(=C1)F
O[CH2:13][CH2:14][CH2:15][NH:16][C:17](=[O:18])[O:19][C:20]([CH3:21])([CH3:22])[CH3:23].[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([F:9])[cH:10][c:11]1[OH:12]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([F:9])[cH:10][c:11]1[O:12][CH2:13][CH2:14][CH2:15][NH:16][C:17](=[O:18])[O:19][C:20]([CH3:21])([CH3:22])[...
CC(C)(C)OC(=O)NCCCO.COC(=O)c1ccc(F)cc1O
COC(=O)c1ccc(F)cc1OCCCNC(=O)OC(C)(C)C
null
null
CCOCC
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1ccccc1
O-[CH2;D2;+0:1]-[C:2]-[C:3].[#8:4]-[C:5](=[O;D1;H0:6])-[c:7]:[c:8](-[OH;D1;+0:9]):[c:10]>>[#8:4]-[C:5](=[O;D1;H0:6])-[c:7]:[c:8](-[O;H0;D2;+0:9]-[CH2;D2;+0:1]-[C:2]-[C:3]):[c:10]
null
[]
null
null
null
null
Using a procedure equivalent to Example 1-F, methyl 4-fluoro-2-hydroxybenzoate and 3-(tert-butoxycarbonylamino)-propanol gave the ether product as a white solid (20.6 g, 84%). Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccccc1
HO-
CCOCC
null
null
CC(C)(C)OC(=O)NCCCO.COC(=O)c1ccc(F)cc1O>CCOCC>COC(=O)c1ccc(F)cc1OCCCNC(=O)OC(C)(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c4ebac061d5e49bf9ec62eaa9b650001
C1COCCN1.COC(=O)c1ccc(F)cc1OCCCNC(=O)OC(C)(C)C>>COC(=O)c1ccc(N2CCOCC2)cc1OCCCNC(=O)OC(C)(C)C
C(C)(C)(C)OC(=O)NCCCOC1=C(C(=O)OC)C=CC(=C1)F.N1CCOCC1>>C(C)(C)(C)OC(=O)NCCCOC1=C(C(=O)OC)C=CC(=C1)N1CCOCC1
[NH:9]1[CH2:10][CH2:11][O:12][CH2:13][CH2:14]1.F[c:8]1[cH:7][cH:6][c:5]([C:3]([O:2][CH3:1])=[O:4])[c:16]([O:17][CH2:18][CH2:19][CH2:20][NH:21][C:22](=[O:23])[O:24][C:25]([CH3:26])([CH3:27])[CH3:28])[cH:15]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([N:9]2[CH2:10][CH2:11][O:12][CH2:13][CH2:14]2)[cH:15][c:16]1[O:...
C1COCCN1.COC(=O)c1ccc(F)cc1OCCCNC(=O)OC(C)(C)C
COC(=O)c1ccc(N2CCOCC2)cc1OCCCNC(=O)OC(C)(C)C
null
null
null
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation secondary amine
a47b7d43ef99c1989f39629bd45f903079b03ac5a9d702fdbffdae93a63a79cd
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc(N2CCOCC2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[#8:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[c:3]:[c:2]:[c;H0;D3;+0:1](-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#8:6]-[C:11]-[C:10]-1):[c:4]:[c:5]
16
[{"value": 16.0, "product": "C(C)(C)(C)OC(=O)NCCCOC1=C(C(=O)OC)C=CC(=C1)N1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}]
130
CELSIUS
null
null
Using methods substantially equivalent to those described in Example 1-G, except that the reaction mixture was heated to 130° C., methyl 2-(3-tert-butoxycarbonylamino-propoxy)-4-(morpholin-4-yl)benzoate (2.39 g, 6.06 mmol, 16%) was prepared from methyl 2-(3-tert-butoxycarbonylamino-propoxy)-4-fluorobenzoate and morphol...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1COCCN1.c1ccccc1
c1ccccc1.C1COCC[NH]1
c1ccccc1.C1COCC[NH]1
HF
null
130
null
C1COCCN1.COC(=O)c1ccc(F)cc1OCCCNC(=O)OC(C)(C)C>>COC(=O)c1ccc(N2CCOCC2)cc1OCCCNC(=O)OC(C)(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f5d7325b9cc94e09804b37d3859053e5
COC(=O)c1ccc(N2CCOCC2)cc1OCCCNC(=O)OC(C)(C)C>>CC(C)(C)OC(=O)NCCCOc1cc(N2CCOCC2)ccc1C(=O)O
C(C)(C)(C)OC(=O)NCCCOC1=C(C(=O)OC)C=CC(=C1)N1CCOCC1.[OH-].[K+]>>C(C)(C)(C)OC(=O)NCCCOC1=C(C(=O)O)C=CC(=C1)N1CCOCC1
C[O:27][C:25]([c:24]1[c:13]([O:12][CH2:11][CH2:10][CH2:9][NH:8][C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[cH:14][c:15]([N:16]2[CH2:17][CH2:18][O:19][CH2:20][CH2:21]2)[cH:22][cH:23]1)=[O:26]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][CH2:9][CH2:10][CH2:11][O:12][c:13]1[cH:14][c:15]([N:16]2[CH2:17][CH...
COC(=O)c1ccc(N2CCOCC2)cc1OCCCNC(=O)OC(C)(C)C
CC(C)(C)OC(=O)NCCCOc1cc(N2CCOCC2)ccc1C(=O)O
null
null
O.C(C)O
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(N2CCOCC2)cc1
C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]>>[O;D1;H0:3]=[C:2](-[OH;D1;+0:1])-[c:4]
99.5
[{"value": 99.0, "product": "C(C)(C)(C)OC(=O)NCCCOC1=C(C(=O)O)C=CC(=C1)N1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 99.5, "product": "C(C)(C)(C)OC(=O)NCCCOC1=C(C(=O)O)C=CC(=C1)N1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
70
CELSIUS
2
HOUR
The methyl 2-(3-tert-butoxycarbonylaminopropoxy)-4-(morpholin-4-yl)benzoate (2.34 g, 5.93 mmol) was diluted with ethanol (60 mL) and water (60 mL). Potassium hydroxide pellets (1.64 g, 29.2 mmol) were added, and the resulting mixture was heated to 70° C. After 2 h, the reaction mixture was concentrated in vacuo. The re...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.C1COCC[NH]1
Other
O.C(C)O
70
2
COC(=O)c1ccc(N2CCOCC2)cc1OCCCNC(=O)OC(C)(C)C>O.C(C)O>CC(C)(C)OC(=O)NCCCOc1cc(N2CCOCC2)ccc1C(=O)O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2ed4140d900344f8850149539ced1594
CC(C)(C)OC(=O)NCCO.CCOC(=O)c1ccc(F)cc1F>>CCOC(=O)c1ccc(F)cc1OCCNC(=O)OC(C)(C)C
FC1=C(C(=O)OCC)C=CC(=C1)F.C(C)(C)(C)OC(=O)NCCO.CC(C)([O-])C.[K+]>>C(C)(C)(C)OC(=O)NCCOC1=C(C(=O)OCC)C=CC(=C1)F
[OH:13][CH2:14][CH2:15][NH:16][C:17](=[O:18])[O:19][C:20]([CH3:21])([CH3:22])[CH3:23].F[c:12]1[c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[cH:7][cH:8][c:9]([F:10])[cH:11]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][cH:8][c:9]([F:10])[cH:11][c:12]1[O:13][CH2:14][CH2:15][NH:16][C:17](=[O:18])[O:19][C:20]([CH3:21])([CH3:22]...
CC(C)(C)OC(=O)NCCO.CCOC(=O)c1ccc(F)cc1F
CCOC(=O)c1ccc(F)cc1OCCNC(=O)OC(C)(C)C
null
null
ClCCl.C1CCOC1
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
4821d6d7238522ee9ef4538c00647e855becf4de3d9c939c0cec2b01c1e5e915
a4cafa7bcd156e21cca6eaac1b32e28ec8540642a31181122e6957f3d7559631
c1ccccc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[C:5](=[O;D1;H0:6])-[#8:7]-[C:8]):[c:9].[C:10]-[C:11]-[OH;D1;+0:12]>>[C:10]-[C:11]-[O;H0;D2;+0:12]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[C:5](=[O;D1;H0:6])-[#8:7]-[C:8]):[c:9]
null
[]
0
CELSIUS
20
MINUTE
To a solution of 2-(tert-butoxycarbonylamino)ethanol (4.34 g, 26.9 mmol) in THF (16 mL) at 0° C. under N2, was added potassium tert-butoxide (K+−OtBu, 26.9 mL, 26.9 mmol, 1.0 M in THF). The reaction mixture was stirred for 20 min at 0° C. during which time a thick slurry formed. The anion solution was then poured into ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol
Ether
c1ccccc1
c1ccccc1
c1ccccc1
HF
ClCCl.C1CCOC1
0
0.333333
CC(C)(C)OC(=O)NCCO.CCOC(=O)c1ccc(F)cc1F>ClCCl.C1CCOC1>CCOC(=O)c1ccc(F)cc1OCCNC(=O)OC(C)(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a225ad6e575f4d5bb1d1fc9cc3450e55
CC(C)(C)OC(=O)NCCOc1cc(N2CCOCC2)ccc1C(=O)O.Nc1cccnc1C(=O)Nc1ccc(Cl)cn1.O=C([O-])C(F)(F)F>>NCCOc1cc(N2CCOCC2)ccc1C(=O)Nc1cccnc1C(=O)Nc1ccc(Cl)cn1.O=C(O)C(F)(F)F
NC=1C(=NC=CC1)C(=O)NC1=NC=C(C=C1)Cl.C(C)(C)(C)OC(=O)NCCOC1=C(C(=O)O)C=CC(=C1)N1CCOCC1.FC(C(=O)[O-])(F)F>>FC(C(=O)O)(F)F.NCCOC1=C(C(=O)NC=2C(=NC=CC2)C(=O)NC2=NC=C(C=C2)Cl)C=CC(=C1)N1CCOCC1
CC(C)(C)OC(=O)[NH:1][CH2:2][CH2:3][O:4][c:5]1[cH:6][c:7]([N:8]2[CH2:9][CH2:10][O:11][CH2:12][CH2:13]2)[cH:14][cH:15][c:16]1[C:17](O)=[O:18].[NH2:19][c:20]1[cH:21][cH:22][cH:23][n:24][c:25]1[C:26](=[O:27])[NH:28][c:29]1[cH:30][cH:31][c:32]([Cl:33])[cH:34][n:35]1.[O:36]=[C:37]([O-:38])[C:39]([F:40])([F:41])[F:42]>>[NH2:1...
CC(C)(C)OC(=O)NCCOc1cc(N2CCOCC2)ccc1C(=O)O.Nc1cccnc1C(=O)Nc1ccc(Cl)cn1.O=C([O-])C(F)(F)F
NCCOc1cc(N2CCOCC2)ccc1C(=O)Nc1cccnc1C(=O)Nc1ccc(Cl)cn1.O=C(O)C(F)(F)F
null
null
CN(C=O)C
Protection
OtherReaction
2697e1cde97ce6b36a4bb65719f859b1cdcabdda76228456baf211310f680305
7be28c2b2dc32b89fb94d0f68f6267f37f885e2da768fcd4882818b94b2ee349
O=C(Nc1cccnc1C(=O)Nc1ccccn1)c1ccc(N2CCOCC2)cc1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2]-[C:3].O-[C;H0;D3;+0:4](=[O;D1;H0:5])-[c:6](:[c:7]):[c:8].[#7:9]-[C:10](=[O;D1;H0:11])-[c:12](:[#7;a:13]:[c:14]):[c:15](-[NH2;D1;+0:16]):[c:17].[F;D1;H0:18]-[C:19](-[F;D1;H0:20])(-[F;D1;H0:21])-[C:22](-[O-;H0;D1:23])=[O;D1;H0:24]>>[#7:9]-[C:10](=[O;D1;H0:11])-[c:12](:[#7;a:13]:[c:1...
2
[{"value": 2.0, "product": "FC(C(=O)O)(F)F.NCCOC1=C(C(=O)NC=2C(=NC=CC2)C(=O)NC2=NC=C(C=C2)Cl)C=CC(=C1)N1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Using methods substantially equivalent to those described in Example 1-I, 3-amino-N-(5-chloropyridin-2-yl)-pyridine-2-carboxamide (321 mg, 1.29 mmol), N,N-dimethyl-formamide (0.2 mL) and 2-(2-tert-butoxycarbonylaminoethoxy)-4-(morpholin-4-yl)benzoic acid (500 mg, 1.36 mmol) yielded, after deprotection of the coupled pr...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Carboxylic acid.Ether.Primary amine.Boc
Carboxylic acid.Secondary amide.Primary amine
null
null
c1ccccc1.C1COCC[NH]1.c1ccncc1.c1ccncc1
HO-
CN(C=O)C
null
null
CC(C)(C)OC(=O)NCCOc1cc(N2CCOCC2)ccc1C(=O)O.Nc1cccnc1C(=O)Nc1ccc(Cl)cn1.O=C([O-])C(F)(F)F>CN(C=O)C>NCCOc1cc(N2CCOCC2)ccc1C(=O)Nc1cccnc1C(=O)Nc1ccc(Cl)cn1.O=C(O)C(F)(F)F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-484c18b173124ccca2ff61658cea3a7d
COC(=O)c1ccncc1NC(=O)c1ccc(N2CCCC2)cc1OC1CCN(C(=O)OC(C)(C)C)CC1>>CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2C(=O)Nc2cnccc2C(=O)O)CC1
C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)NC=2C=NC=CC2C(=O)OC)C=CC(=C1)N1CCCC1.[OH-].[Na+]>>C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)NC=2C=NC=CC2C(=O)O)C=CC(=C1)N1CCCC1
C[O:35][C:33]([c:32]1[c:27]([NH:26][C:24]([c:23]2[c:13]([O:12][CH:11]3[CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:37][CH2:36]3)[cH:14][c:15]([N:16]3[CH2:17][CH2:18][CH2:19][CH2:20]3)[cH:21][cH:22]2)=[O:25])[cH:28][n:29][cH:30][cH:31]1)=[O:34]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:...
COC(=O)c1ccncc1NC(=O)c1ccc(N2CCCC2)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2C(=O)Nc2cnccc2C(=O)O)CC1
null
null
CO.C1CCOC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(Nc1cccnc1)c1ccc(N2CCCC2)cc1OC1CCNCC1
C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]>>[O;D1;H0:3]=[C:2](-[OH;D1;+0:1])-[c:4]
null
[]
null
null
4
HOUR
A solution of methyl 3-[2-(1-tert-butoxycarbonyl-piperidin-4-yloxy)-4-(pyrrolidin-1-yl)benzoylamino]pyridine-4-carboxylate (2.78 g, 5.3 mmol) in MeOH (100 mL) and THF (50 mL) was treated with 1 N NaOH (11 mL) and stirred at ambient temperature for 4 h. The reaction was quenched with glacial acetic acid (1 g) and concen...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CC[NH]CC1.c1ccccc1.C1CC[NH]C1.c1ccncc1
Other
CO.C1CCOC1
null
4
COC(=O)c1ccncc1NC(=O)c1ccc(N2CCCC2)cc1OC1CCN(C(=O)OC(C)(C)C)CC1>CO.C1CCOC1>CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2C(=O)Nc2cnccc2C(=O)O)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5575b543a6ca43cabe4e4beafdc4cd23
CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2-c2nc3cnccc3c(=O)o2)CC1.Nc1ccc(Cl)cn1>>CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2C(=O)Nc2cnccc2C(=O)Nc2ccc(Cl)cn2)CC1
C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C=CC(=C1)N1CCCC1)C=1OC(C2=C(N1)C=NC=C2)=O.C(C)OCC.C(C=C)[Mg]Br.NC1=NC=C(C=C1)Cl>>C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)NC=2C=NC=CC2C(=O)NC2=NC=C(C=C2)Cl)C=CC(=C1)N1CCCC1
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH:11]([O:12][c:13]2[cH:14][c:15]([N:16]3[CH2:17][CH2:18][CH2:19][CH2:20]3)[cH:21][cH:22][c:23]2-[c:24]2[o:25][c:33](=[O:34])[c:32]3[c:27]([n:26]2)[cH:28][n:29][cH:30][cH:31]3)[CH2:43][CH2:44]1.[NH2:35][c:36]1[cH:37][cH:38][c:39]([Cl:40])[cH:41][n:42...
CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2-c2nc3cnccc3c(=O)o2)CC1.Nc1ccc(Cl)cn1
CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2C(=O)Nc2cnccc2C(=O)Nc2ccc(Cl)cn2)CC1
null
null
C1CCOC1
Acylation
OtherReaction
b47b3587e7ae57e8006790ee803a5e0f02b71ebe0cd3e0556d0df0fb445694e1
4accd3f274dad8ca7d44350b7d7da15181b5e5579c068528178b23416d2aea4a
O=C(Nc1ccccn1)c1ccncc1NC(=O)c1ccc(N2CCCC2)cc1OC1CCNCC1
[#8:1]-[c:2](:[c:3]):[c;H0;D3;+0:4](-[c;H0;D3;+0:5]1:[n;H0;D2;+0:6]:[c:7]2:[c:8]:[#7;a:9]:[c:10]:[c:11]:[c:12]:2:[c;H0;D3;+0:13](=[O;D1;H0:14]):[o;H0;D2;+0:15]:1):[c:16]:[c:17].[NH2;D1;+0:18]-[c:19](:[c:20]):[#7;a:21]:[c:22]>>[#8:1]-[c:2](:[c:3]):[c;H0;D3;+0:4](-[C;H0;D3;+0:5](=[O;H0;D1;+0:15])-[NH;D2;+0:6]-[c:7]1:[c:8...
100
[{"value": 99.0, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)NC=2C=NC=CC2C(=O)NC2=NC=C(C=C2)Cl)C=CC(=C1)N1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 100.0, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)NC=2C=NC=CC2C(=O)NC2=NC=C(C=C2)Cl)C=CC(=C1)N1CCCC1", "details": "CALCULATEDPERCENTYIEL...
null
null
5
MINUTE
A solution of 2-amino-5-chloropyridine (52 mg, 0.4 mmol) in THF (10 mL) was cooled to 0° C. and treated with a 1 M diethyl ether solution of allylmagnesium bromide (0.4 mL). The mixture was stirred for 5 minutes before adding 2-[2-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-(pyrrolidin-1-yl)phenyl]-4H-pyrido[3,4-d][1,3]...
10.6084/m9.figshare.5104873.v1
null
Primary amine
Secondary amide.Secondary amide
c1nc2cnccc2co1
c1ccncc1
C1CC[NH]CC1.c1ccccc1.C1CC[NH]C1.c1ccncc1.c1ccncc1
null
C1CCOC1
null
0.083333
CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2-c2nc3cnccc3c(=O)o2)CC1.Nc1ccc(Cl)cn1>C1CCOC1>CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2C(=O)Nc2cnccc2C(=O)Nc2ccc(Cl)cn2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ccc603e9536e469d9837ac6520ce0c29
CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2C(=O)Nc2cnccc2C(=O)Nc2ccc(Cl)cn2)CC1>>O=C(Nc1ccc(Cl)cn1)c1ccncc1NC(=O)c1ccc(N2CCCC2)cc1OC1CCNCC1
C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)NC=2C=NC=CC2C(=O)NC2=NC=C(C=C2)Cl)C=CC(=C1)N1CCCC1.FC(C(=O)O)(F)F>>FC(C(=O)O)(F)F.ClC=1C=CC(=NC1)NC(=O)C1=C(C=NC=C1)NC(C1=C(C=C(C=C1)N1CCCC1)OC1CCNCC1)=O
CC(C)(C)OC(=O)[N:35]1[CH2:34][CH2:33][CH:32]([O:31][c:30]2[c:20]([C:18]([NH:17][c:16]3[c:11]([C:2](=[O:1])[NH:3][c:4]4[cH:5][cH:6][c:7]([Cl:8])[cH:9][n:10]4)[cH:12][cH:13][n:14][cH:15]3)=[O:19])[cH:21][cH:22][c:23]([N:24]3[CH2:25][CH2:26][CH2:27][CH2:28]3)[cH:29]2)[CH2:37][CH2:36]1>>[O:1]=[C:2]([NH:3][c:4]1[cH:5][cH:6]...
CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2C(=O)Nc2cnccc2C(=O)Nc2ccc(Cl)cn2)CC1
O=C(Nc1ccc(Cl)cn1)c1ccncc1NC(=O)c1ccc(N2CCCC2)cc1OC1CCNCC1
null
null
C1(=CC=CC=C1)OC.C(Cl)Cl
Reduction
Boc amine deprotection
bf3cd5dc3e17e694d8665c89f5d7e08e8763b18436a633eb66e9bf530b8b0316
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
O=C(Nc1ccccn1)c1ccncc1NC(=O)c1ccc(N2CCCC2)cc1OC1CCNCC1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1](-[C:2]-[C:3])-[C:4]-[C:5]>>[C:3]-[C:2]-[NH;D2;+0:1]-[C:4]-[C:5]
89
[{"value": 89.0, "product": "FC(C(=O)O)(F)F.ClC=1C=CC(=NC1)NC(=O)C1=C(C=NC=C1)NC(C1=C(C=C(C=C1)N1CCCC1)OC1CCNCC1)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The 3-[2-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-(pyrrolidin-1-yl)benzoylamino]-N-(5-chloropyridin-2-yl)-pyridine-4-carboxamide (109 mg, 0.18 mmol) was dissolved in CH2Cl2 (2 mL) with anisole (1 mL). The solution was treated with trifluoroacetic acid (1 mL) at room temperature for 2 h. The mixture was concentrated t...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
C1CC[NH]CC1
C1CCNCC1
c1ccncc1.c1ccncc1.c1ccccc1.C1CC[NH]C1.C1CCNCC1
HO-
C1(=CC=CC=C1)OC.C(Cl)Cl
null
null
CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2C(=O)Nc2cnccc2C(=O)Nc2ccc(Cl)cn2)CC1>C1(=CC=CC=C1)OC.C(Cl)Cl>O=C(Nc1ccc(Cl)cn1)c1ccncc1NC(=O)c1ccc(N2CCCC2)cc1OC1CCNCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-871b6393702f46e4bccf3ff3709423c2
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2-c2nc3cnccc3c(=O)o2)CC1.Nc1ccc(Cl)cn1>>CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)Nc2cnccc2C(=O)Nc2ccc(Cl)cn2)CC1
C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C=CC(=C1)C(C)(C)C)C=1OC(C2=C(N1)C=NC=C2)=O.[C-]#N.[K+].ClC=1C=CC(=NC1)N>>C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)NC=2C=NC=CC2C(=O)NC2=NC=C(C=C2)Cl)C=CC(=C1)C(C)(C)C
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH:11]([O:12][c:13]2[cH:14][c:15]([C:16]([CH3:17])([CH3:18])[CH3:19])[cH:20][cH:21][c:22]2-[c:23]2[o:24][c:32](=[O:33])[c:31]3[c:26]([n:25]2)[cH:27][n:28][cH:29][cH:30]3)[CH2:42][CH2:43]1.[NH2:34][c:35]1[cH:36][cH:37][c:38]([Cl:39])[cH:40][n:41]1>>[C...
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2-c2nc3cnccc3c(=O)o2)CC1.Nc1ccc(Cl)cn1
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)Nc2cnccc2C(=O)Nc2ccc(Cl)cn2)CC1
null
null
CN(C)C=O
Acylation
OtherReaction
b47b3587e7ae57e8006790ee803a5e0f02b71ebe0cd3e0556d0df0fb445694e1
4accd3f274dad8ca7d44350b7d7da15181b5e5579c068528178b23416d2aea4a
O=C(Nc1ccccn1)c1ccncc1NC(=O)c1ccccc1OC1CCNCC1
[#8:1]-[c:2](:[c:3]):[c;H0;D3;+0:4](-[c;H0;D3;+0:5]1:[n;H0;D2;+0:6]:[c:7]2:[c:8]:[#7;a:9]:[c:10]:[c:11]:[c:12]:2:[c;H0;D3;+0:13](=[O;D1;H0:14]):[o;H0;D2;+0:15]:1):[c:16]:[c:17].[NH2;D1;+0:18]-[c:19](:[c:20]):[#7;a:21]:[c:22]>>[#8:1]-[c:2](:[c:3]):[c;H0;D3;+0:4](-[C;H0;D3;+0:5](=[O;H0;D1;+0:15])-[NH;D2;+0:6]-[c:7]1:[c:8...
23.5
[{"value": 23.5, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)NC=2C=NC=CC2C(=O)NC2=NC=C(C=C2)Cl)C=CC(=C1)C(C)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
70
CELSIUS
null
null
A mixture of 2-[2-(1-tert-butoxycarbonylpiperidin-4-yl-oxy)-4-tert-butylphenyl]-4H-pyrido[3,4-d][1,3]oxazin-4-one (100 mg, 0.21 mmol), KCN (100 mg), 5-chloro-2-aminopyridine (53 mg, 0.42 mmol), and dry DMF (2 mL) was heated at 70° C. for 4 h, then quenched with brine (25 mL). The mixture was extracted with 10% MQOH in ...
10.6084/m9.figshare.5104873.v1
null
Primary amine
Secondary amide.Secondary amide
c1nc2cnccc2co1
c1ccncc1
C1CC[NH]CC1.c1ccccc1.c1ccncc1.c1ccncc1
null
CN(C)C=O
70
null
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2-c2nc3cnccc3c(=O)o2)CC1.Nc1ccc(Cl)cn1>CN(C)C=O>CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)Nc2cnccc2C(=O)Nc2ccc(Cl)cn2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b8dcbc4583734b79ac012a5a7b4eaf05
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)Nc2cnccc2C(=O)Nc2ccc(Cl)cn2)CC1>>CC(C)(C)c1ccc(C(=O)Nc2cnccc2C(=O)Nc2ccc(Cl)cn2)c(OC2CCNCC2)c1
C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)NC=2C=NC=CC2C(=O)NC2=NC=C(C=C2)Cl)C=CC(=C1)C(C)(C)C.C1(=CC=CC=C1)OC.FC(C(=O)O)(F)F>>C(C)(C)(C)C1=CC(=C(C(=O)NC=2C=NC=CC2C(=O)NC2=NC=C(C=C2)Cl)C=C1)OC1CCNCC1
CC(C)(C)OC(=O)[N:33]1[CH2:32][CH2:31][CH:30]([O:29][c:28]2[c:8]([C:9](=[O:10])[NH:11][c:12]3[cH:13][n:14][cH:15][cH:16][c:17]3[C:18](=[O:19])[NH:20][c:21]3[cH:22][cH:23][c:24]([Cl:25])[cH:26][n:27]3)[cH:7][cH:6][c:5]([C:2]([CH3:1])([CH3:3])[CH3:4])[cH:36]2)[CH2:35][CH2:34]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[c:5]1[cH:6][c...
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)Nc2cnccc2C(=O)Nc2ccc(Cl)cn2)CC1
CC(C)(C)c1ccc(C(=O)Nc2cnccc2C(=O)Nc2ccc(Cl)cn2)c(OC2CCNCC2)c1
null
null
C(Cl)Cl
Reduction
Boc amine deprotection
bf3cd5dc3e17e694d8665c89f5d7e08e8763b18436a633eb66e9bf530b8b0316
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
O=C(Nc1ccccn1)c1ccncc1NC(=O)c1ccccc1OC1CCNCC1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1](-[C:2]-[C:3])-[C:4]-[C:5]>>[C:3]-[C:2]-[NH;D2;+0:1]-[C:4]-[C:5]
63
[{"value": 63.0, "product": "C(C)(C)(C)C1=CC(=C(C(=O)NC=2C=NC=CC2C(=O)NC2=NC=C(C=C2)Cl)C=C1)OC1CCNCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
4
HOUR
The 3-[2-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-(tert-butyl)benzoylamino]-N-(5-chloropyridin-2-yl)pyridine-4-carboxamide (60 mg, 0.1 mmol) was mixed with anisole (1 mL) and CH2Cl2 (2 mL) then treated with trifluoroacetic acid (1 mL). The reaction was stirred at ambient temperature for 4 h, concentrated under vacuum...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
C1CC[NH]CC1
C1CCNCC1
c1ccccc1.c1ccncc1.c1ccncc1.C1CCNCC1
HO-
C(Cl)Cl
null
4
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)Nc2cnccc2C(=O)Nc2ccc(Cl)cn2)CC1>C(Cl)Cl>CC(C)(C)c1ccc(C(=O)Nc2cnccc2C(=O)Nc2ccc(Cl)cn2)c(OC2CCNCC2)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ab34c9d7e1bb44e1bf823119269e3b8a
CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2C(=O)O)CC1.COC(=O)c1sccc1N>>COC(=O)c1sccc1NC(=O)c1ccc(N2CCCC2)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
C(C)(C)(C)ON1C(CC(CC1)OC1=C(C(=O)NC2=C(SC=C2)C(=O)OC)C=CC(=C1)N1CCCC1)=C=O.C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)O)C=CC(=C1)N1CCCC1.NC1=C(SC=C1)C(=O)OC>>C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)NC2=C(SC=C2)C(=O)OC)C=CC(=C1)N1CCCC1
O[C:11](=[O:12])[c:13]1[cH:14][cH:15][c:16]([N:17]2[CH2:18][CH2:19][CH2:20][CH2:21]2)[cH:22][c:23]1[O:24][CH:25]1[CH2:26][CH2:27][N:28]([C:29](=[O:30])[O:31][C:32]([CH3:33])([CH3:34])[CH3:35])[CH2:36][CH2:37]1.[CH3:1][O:2][C:3](=[O:4])[c:5]1[s:6][cH:7][cH:8][c:9]1[NH2:10]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[s:6][cH:7][cH:...
CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2C(=O)O)CC1.COC(=O)c1sccc1N
COC(=O)c1sccc1NC(=O)c1ccc(N2CCCC2)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
null
null
null
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(Nc1ccsc1)c1ccc(N2CCCC2)cc1OC1CCNCC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[#8:6]-[C:7](=[O;D1;H0:8])-[c:9]1:[#16;a:10]:[c:11]:[c:12]:[c:13]:1-[NH2;D1;+0:14]>>[#8:6]-[C:7](=[O;D1;H0:8])-[c:9]1:[#16;a:10]:[c:11]:[c:12]:[c:13]:1-[NH;D2;+0:14]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
58
[{"value": 58.0, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)NC2=C(SC=C2)C(=O)OC)C=CC(=C1)N1CCCC1", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Using methods substantially equivalent to those described in Example 12-C, methyl 3-[2-(1-tert-butoxy-carbonylpiperidin-4-yloxy)-4-(pyrrolidin-1-yl)benzoylamino]-thiophene-2-carboxylate was prepared in a 58% yield from 2-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-(pyrrolidin-1-yl)benzoic acid and methyl 3-aminothiophen...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccsc1.c1ccccc1.C1CC[NH]C1.C1CC[NH]CC1
HO-
null
null
null
CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2C(=O)O)CC1.COC(=O)c1sccc1N>>COC(=O)c1sccc1NC(=O)c1ccc(N2CCCC2)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e4eb1700d8884e7e92062637cba3ef88
COC(=O)c1sccc1NC(=O)c1ccc(N2CCCC2)cc1OC1CCN(C(=O)OC(C)(C)C)CC1>>CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2C(=O)Nc2ccsc2C(=O)O)CC1
C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)NC2=C(SC=C2)C(=O)OC)C=CC(=C1)N1CCCC1.CCO.[OH-].[K+]>>C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)NC2=C(SC=C2)C(=O)O)C=CC(=C1)N1CCCC1
C[O:34][C:32]([c:31]1[c:27]([NH:26][C:24]([c:23]2[c:13]([O:12][CH:11]3[CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:36][CH2:35]3)[cH:14][c:15]([N:16]3[CH2:17][CH2:18][CH2:19][CH2:20]3)[cH:21][cH:22]2)=[O:25])[cH:28][cH:29][s:30]1)=[O:33]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8...
COC(=O)c1sccc1NC(=O)c1ccc(N2CCCC2)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2C(=O)Nc2ccsc2C(=O)O)CC1
null
null
O
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(Nc1ccsc1)c1ccc(N2CCCC2)cc1OC1CCNCC1
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]
94.4
[{"value": 94.0, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)NC2=C(SC=C2)C(=O)O)C=CC(=C1)N1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 94.4, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)NC2=C(SC=C2)C(=O)O)C=CC(=C1)N1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of the methyl 3-[2-(1-tert-butoxycarbonyl-piperidin-4-yloxy)-4-(pyrrolidin-1-yl)benzoylamino]-thiophene-2-carboxylate (3.8 g, 7.2 mmol) and EtOH (100 mL) was treated with a solution of KOH (0.88 g) in water (80 mL). The reaction mixture was refluxed overnight, quenched with glacial acetic acid (1.5 mL) and c...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CC[NH]CC1.c1ccccc1.C1CC[NH]C1.c1ccsc1
Other
O
null
null
COC(=O)c1sccc1NC(=O)c1ccc(N2CCCC2)cc1OC1CCN(C(=O)OC(C)(C)C)CC1>O>CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2C(=O)Nc2ccsc2C(=O)O)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d3a29ac2466649be9f7409d0a2015af4
CN(C)C=O.COC(=O)c1ccc(F)cc1OC1CCN(C(=O)OC(C)(C)C)CC1>>COC(=O)c1ccc(N(C)C)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
CN(C)C=O.C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)OC)C=CC(=C1)F.N1CCOCC1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O>>C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)OC)C=CC(=C1)N(C)C
O=C[N:9]([CH3:10])[CH3:11].F[c:8]1[cH:7][cH:6][c:5]([C:3]([O:2][CH3:1])=[O:4])[c:13]([O:14][CH:15]2[CH2:16][CH2:17][N:18]([C:19](=[O:20])[O:21][C:22]([CH3:23])([CH3:24])[CH3:25])[CH2:26][CH2:27]2)[cH:12]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([N:9]([CH3:10])[CH3:11])[cH:12][c:13]1[O:14][CH:15]1[CH2:16][CH2:...
CN(C)C=O.COC(=O)c1ccc(F)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
COC(=O)c1ccc(N(C)C)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
null
null
[Cl-].[Na+].O
Heteroatom Alkylation and Arylation
OtherReaction
79e5fcace80b85c39b8b97f2b6fb84586538378f01cb44375f57f3ff58a947fa
da441520990db3b7dfc8421b343d1a69dceb643d35ca5c86f0c23a5d017d38e3
c1ccc(OC2CCNCC2)cc1
F-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].O=C-[N;H0;D3;+0:6](-[C;D1;H3:7])-[C;D1;H3:8]>>[C;D1;H3:7]-[N;H0;D3;+0:6](-[C;D1;H3:8])-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]
59
[{"value": 59.0, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)OC)C=CC(=C1)N(C)C", "details": "PERCENTYIELD", "is_desired": false}]
110
CELSIUS
null
null
The 4-dimethylamino compound was obtained in the following preparation in which the dimethylamino group was derived from in situ decomposition of the solvent DMF: A mixture of methyl 2-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-fluorobenzoate (6.45 g, 18.25 mmol), morpholine (8 g, 91.26 mmol), Cs2CO3 (11.8 g, 36.5 mmol...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Tertiary amide
Tertiary amine
c1ccccc1
c1ccccc1
c1ccccc1.C1CC[NH]CC1
HF
[Cl-].[Na+].O
110
null
CN(C)C=O.COC(=O)c1ccc(F)cc1OC1CCN(C(=O)OC(C)(C)C)CC1>[Cl-].[Na+].O>COC(=O)c1ccc(N(C)C)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ca0abe26feb74a2bbda23271876d02b4
CN(C)c1ccc(C(=O)O)c(OC2CCN(C(=O)OC(C)(C)C)CC2)c1.COC(=O)c1cscc1N>>COC(=O)c1cscc1NC(=O)c1ccc(N(C)C)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
C(C)(C)(C)ON1C(CC(CC1)OC1=C(C(=O)NC=2C(=CSC2)C(=O)OC)C=CC(=C1)N(C)C)=C=O.C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)O)C=CC(=C1)N(C)C.NC=1C(=CSC1)C(=O)OC>>C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)NC=2C(=CSC2)C(=O)OC)C=CC(=C1)N(C)C
O[C:11](=[O:12])[c:13]1[cH:14][cH:15][c:16]([N:17]([CH3:18])[CH3:19])[cH:20][c:21]1[O:22][CH:23]1[CH2:24][CH2:25][N:26]([C:27](=[O:28])[O:29][C:30]([CH3:31])([CH3:32])[CH3:33])[CH2:34][CH2:35]1.[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][s:7][cH:8][c:9]1[NH2:10]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][s:7][cH:8][c:9]1[NH:10][...
CN(C)c1ccc(C(=O)O)c(OC2CCN(C(=O)OC(C)(C)C)CC2)c1.COC(=O)c1cscc1N
COC(=O)c1cscc1NC(=O)c1ccc(N(C)C)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
null
null
null
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(Nc1ccsc1)c1ccccc1OC1CCNCC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[#8:6]-[C:7](=[O;D1;H0:8])-[c:9]1:[c:10]:[#16;a:11]:[c:12]:[c:13]:1-[NH2;D1;+0:14]>>[#8:6]-[C:7](=[O;D1;H0:8])-[c:9]1:[c:10]:[#16;a:11]:[c:12]:[c:13]:1-[NH;D2;+0:14]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
51
[{"value": 51.0, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)NC=2C(=CSC2)C(=O)OC)C=CC(=C1)N(C)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Using methods substantially equivalent to those described in Example 12-C, methyl 4-[2-(1-tert-butoxy-carbonylpiperidin-4-yloxy)-4-(dimethylamino)benzoylamino]-thiophene-3-carboxylate was prepared in a 51% yield from 2-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-(dimethyl-amino)benzoic acid and methyl 4-aminothiophene-3...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccsc1.c1ccccc1.C1CC[NH]CC1
HO-
null
null
null
CN(C)c1ccc(C(=O)O)c(OC2CCN(C(=O)OC(C)(C)C)CC2)c1.COC(=O)c1cscc1N>>COC(=O)c1cscc1NC(=O)c1ccc(N(C)C)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1c025f3a95bc4e6b86e1a8dfda099309
COC(=O)c1cscc1NC(=O)c1ccc(N(C)C)cc1OC1CCN(C(=O)OC(C)(C)C)CC1>>CN(C)c1ccc(-c2nc3cscc3c(=O)o2)c(OC2CCN(C(=O)OC(C)(C)C)CC2)c1
C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)NC=2C(=CSC2)C(=O)OC)C=CC(=C1)N(C)C.[OH-].[Na+]>>C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C=CC(=C1)N(C)C)C=1OC(C=2C(N1)=CSC2)=O
CO[C:15]([c:14]1[c:10]([NH:9][C:8]([c:7]2[cH:6][cH:5][c:4]([N:2]([CH3:1])[CH3:3])[cH:33][c:18]2[O:19][CH:20]2[CH2:21][CH2:22][N:23]([C:24](=[O:25])[O:26][C:27]([CH3:28])([CH3:29])[CH3:30])[CH2:31][CH2:32]2)=[O:17])[cH:11][s:12][cH:13]1)=[O:16]>>[CH3:1][N:2]([CH3:3])[c:4]1[cH:5][cH:6][c:7](-[c:8]2[n:9][c:10]3[cH:11][s:1...
COC(=O)c1cscc1NC(=O)c1ccc(N(C)C)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
CN(C)c1ccc(-c2nc3cscc3c(=O)o2)c(OC2CCN(C(=O)OC(C)(C)C)CC2)c1
null
null
CO.C1CCOC1
Aromatic Heterocycle Formation
OtherReaction
f165d441235a395ef6db5f790e934e063854e912f9b5233524dc0f2cf0d523a0
2fd2cda60f919882649147d24290e6fb253175d1342fb909035293b0bba9a63a
O=c1oc(-c2ccccc2OC2CCNCC2)nc2cscc12
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3]1:[c:4]:[#16;a:5]:[c:6]:[c:7]:1-[NH;D2;+0:8]-[C;H0;D3;+0:9](=[O;H0;D1;+0:10])-[c;H0;D3;+0:11](:[c:12]:[c:13]):[c:14](-[#8:15]):[c:16]>>[#8:15]-[c:14](:[c:16]):[c;H0;D3;+0:11](-[c;H0;D3;+0:9]1:[n;H0;D2;+0:8]:[c:7]2:[c:6]:[#16;a:5]:[c:4]:[c:3]:2:[c;H0;D3;+0:1](=[O;D1;H0:2]):[o;H0;D2;...
92.2
[{"value": 92.2, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C=CC(=C1)N(C)C)C=1OC(C=2C(N1)=CSC2)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
8
HOUR
A solution of methyl 4-[2-(1-tert-butoxycarbonyl-piperidin-4-yloxy)-4-(dimethylamino)benzoylamino]thiophene-3-carboxylate (2.3 g, 4.6 mmol) in MeOH (100 mL) and THF (50 mL) was treated with a solution of 1 N aqueous NaOH (10 mL) at 60° C. for 24 h. The mixture was concentrated to dryness, mixed with brine (25 mL) and g...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary amide
null
c1ccsc1
c1nc2cscc2co1
c1ccccc1.c1nc2cscc2co1.C1CC[NH]CC1
HO-
CO.C1CCOC1
0
8
COC(=O)c1cscc1NC(=O)c1ccc(N(C)C)cc1OC1CCN(C(=O)OC(C)(C)C)CC1>CO.C1CCOC1>CN(C)c1ccc(-c2nc3cscc3c(=O)o2)c(OC2CCN(C(=O)OC(C)(C)C)CC2)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-6dec4c08d411456ebba835a408a5e987
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)O)CC1>>CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2CO)CC1
[B-][N+](C)(C)C.C(C)(C)(C)C1=CC(=C(C(=O)O)C=C1)OC1CCN(CC1)C(=O)OC(C)(C)C.[B-][N+](C)(C)C>>C(C)(C)(C)C1=CC(=C(CO)C=C1)OC1CCN(CC1)C(=O)OC(C)(C)C
O=[C:23]([c:22]1[c:13]([O:12][CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:26][CH2:25]2)[cH:14][c:15]([C:16]([CH3:17])([CH3:18])[CH3:19])[cH:20][cH:21]1)[OH:24]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH:11]([O:12][c:13]2[cH:14][c:15]([C:16]([CH3:17])(...
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)O)CC1
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2CO)CC1
null
null
O1CCCC1
Reduction
Reduction of carboxylic acid to primary alcohol
0db83a5ebe1e318b78b55461cf7eb8f7c004eef0f9e3b6666d3df4c96b5f665e
93b4621647b04d2ad2f2825215b1567f171ba61fe10d136b5db6ea0470aa4932
c1ccc(OC2CCNCC2)cc1
O=[C;H0;D3;+0:1](-[O;D1;H1:2])-[c:3](:[c:4]):[c:5]>>[O;D1;H1:2]-[CH2;D2;+0:1]-[c:3](:[c:4]):[c:5]
null
[]
null
null
4
HOUR
The alcohol may be prepared as follows: To a solution of borane-trimethylamine complex (1.35 mL of a 1 M solution in tetrahydrofuran) in tetrahydrofuran (3 mL) stirring at 0° C., a solution of 4-tert-butyl-2-(1-Boc-piperidine-4-yl-oxy)benzoic acid (0.51 g, 1.35 mmol) in tetrahydrofuran (7 mL) was added slowly via cannu...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
Primary alcohol
null
null
C1CC[NH]CC1.c1ccccc1
Other
O1CCCC1
null
4
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)O)CC1>O1CCCC1>CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2CO)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-00a42f08ec8c43148c1375dbb7365c1d
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2CN2C(=O)c3ccccc3C2=O)CC1>>CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2CN)CC1
C(C)(C)(C)C1=CC(=C(CN2C(C=3C(C2=O)=CC=CC3)=O)C=C1)OC1CCN(CC1)C(=O)OC(C)(C)C.NN>>C(C)(C)(C)C1=CC(=C(CN)C=C1)OC1CCN(CC1)C(=O)OC(C)(C)C
O=C1c2ccccc2C(=O)[N:24]1[CH2:23][c:22]1[c:13]([O:12][CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:26][CH2:25]2)[cH:14][c:15]([C:16]([CH3:17])([CH3:18])[CH3:19])[cH:20][cH:21]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH:11]([O:12][c:13]2[cH:14][c:15]([C...
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2CN2C(=O)c3ccccc3C2=O)CC1
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2CN)CC1
null
null
C(Cl)Cl.C(C)O
Reduction
Phthalimide deprotection
d9f63cee80ef758bd939ff2a10772447b3092f1576180488281833a98eb1691a
dbfe4201a9328005dfaec4c3f363ddbb4ef3c9b825f648735dc97b2b57396333
c1ccc(OC2CCNCC2)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]
95.7
[{"value": 95.0, "product": "C(C)(C)(C)C1=CC(=C(CN)C=C1)OC1CCN(CC1)C(=O)OC(C)(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 95.7, "product": "C(C)(C)(C)C1=CC(=C(CN)C=C1)OC1CCN(CC1)C(=O)OC(C)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
To a solution of N-[4-tert-butyl-2-(1-Boc-piperidin-4-yloxy)benzyl]phthalimide (0.243 g, 0.49 mmol) in 3 mL absolute ethanol was added hydrazine (0.062 mL, 1.98 mmol) at room temperature. The reaction mixture was stirred at room temperature for 2 h, diluted with methylene chloride; and the resulting white solid filtere...
10.6084/m9.figshare.5104873.v1
null
Substituted dicarboximide
Primary amine
c1ccc2c(c1)C[NH]C2
null
C1CC[NH]CC1.c1ccccc1
HO-
C(Cl)Cl.C(C)O
null
2
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2CN2C(=O)c3ccccc3C2=O)CC1>C(Cl)Cl.C(C)O>CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2CN)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ee29ab3c79d147be90897a0680970a2d
Nc1ccc(Cl)cc1.O=C(Cl)c1cccnc1>>O=C(Nc1ccc(Cl)cc1)c1cccnc1Cl
C(C1=CN=CC=C1)(=O)Cl.ClC1=CC=C(N)C=C1.C(C)N(CC)CC.ClCCCl>>ClC1=CC=C(C=C1)NC(C1=C(N=CC=C1)Cl)=O
[NH2:3][c:4]1[cH:5][cH:6][c:7]([Cl:8])[cH:9][cH:10]1.[O:1]=[C:2]([c:11]1[cH:12][cH:13][cH:14][n:15][cH:16]1)[Cl:17]>>[O:1]=[C:2]([NH:3][c:4]1[cH:5][cH:6][c:7]([Cl:8])[cH:9][cH:10]1)[c:11]1[cH:12][cH:13][cH:14][n:15][c:16]1[Cl:17]
Nc1ccc(Cl)cc1.O=C(Cl)c1cccnc1
O=C(Nc1ccc(Cl)cc1)c1cccnc1Cl
null
null
null
Acylation
OtherReaction
b8b801d661aa1b765ccba3a9581618fcedc62dc62d7673fcb9123336188f178d
66a2d985d0feddf4cfbcfcda0552b4c93401dee4e39ffbe91f30ac58e186e158
O=C(Nc1ccccc1)c1cccnc1
[Cl;H0;D1;+0:1]-[C;H0;D3;+0:2](=[O;D1;H0:3])-[c:4](:[c:5]):[cH;D2;+0:6]:[#7;a:7]:[c:8].[NH2;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:6](:[#7;a:7]:[c:8]):[c:4](-[C;H0;D3;+0:2](=[O;D1;H0:3])-[NH;D2;+0:9]-[c:10](:[c:11]):[c:12]):[c:5]
100
[{"value": 100.0, "product": "ClC1=CC=C(C=C1)NC(C1=C(N=CC=C1)Cl)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
To a solution of nicotinoyl chloride (0.500 g, 2.84 mmol) in 15 mL of 1,2-dichloroethane was added 4-chloroaniline (0.432 g, 3.41 mmol) and triethylamine (0.400 mL, 2.84 mmol), respectively. The reaction mixture was stirred at room temperature for 1 h before it was washed with water (2×), brine (1×), dried over Na2SO4,...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amine
Aromatic halide.Secondary amide
c1ccncc1
c1ccncc1
c1ccccc1.c1ccncc1
null
null
null
1
Nc1ccc(Cl)cc1.O=C(Cl)c1cccnc1>>O=C(Nc1ccc(Cl)cc1)c1cccnc1Cl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-dff22854df074758802314edeec71394
COCOc1cc(C(C)C)ccc1C(=O)O>>COCOc1cc(C(C)C)ccc1CO
C(C)(C)C1=CC(=C(C(=O)O)C=C1)OCOC.CN1CCOCC1.[BH4-].[Na+].ClC(=O)OCC.C(=O)=O>>C(C)(C)C1=CC(=C(CO)C=C1)OCOC
O=[C:14]([c:13]1[c:5]([O:4][CH2:3][O:2][CH3:1])[cH:6][c:7]([CH:8]([CH3:9])[CH3:10])[cH:11][cH:12]1)[OH:15]>>[CH3:1][O:2][CH2:3][O:4][c:5]1[cH:6][c:7]([CH:8]([CH3:9])[CH3:10])[cH:11][cH:12][c:13]1[CH2:14][OH:15]
COCOc1cc(C(C)C)ccc1C(=O)O
COCOc1cc(C(C)C)ccc1CO
null
null
O1CCCC1.CO
Reduction
Reduction of carboxylic acid to primary alcohol
0db83a5ebe1e318b78b55461cf7eb8f7c004eef0f9e3b6666d3df4c96b5f665e
93b4621647b04d2ad2f2825215b1567f171ba61fe10d136b5db6ea0470aa4932
c1ccccc1
O=[C;H0;D3;+0:1](-[O;D1;H1:2])-[c:3](:[c:4]):[c:5]>>[O;D1;H1:2]-[CH2;D2;+0:1]-[c:3](:[c:4]):[c:5]
50
[{"value": 50.0, "product": "C(C)(C)C1=CC(=C(CO)C=C1)OCOC", "details": "PERCENTYIELD", "is_desired": false}]
-10
CELSIUS
20
MINUTE
To a solution of 4-isopropyl-2-(methoxymethoxy)benzoic acid, which may be prepared as described in Exmple 6-B, (2.40 g, 11.0 mmol) and 4-methylmorpholine (1.18 mL, 11.0 mmol) in 50 mL dry tetrahydrofuran at −10° C. was added dropwise ethyl chloroformate (1.02 mL, 11.0 mmol). After stirring at −10° C. for 20 min, sodium...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
Primary alcohol
null
null
c1ccccc1
Other
O1CCCC1.CO
-10
0.333333
COCOc1cc(C(C)C)ccc1C(=O)O>O1CCCC1.CO>COCOc1cc(C(C)C)ccc1CO
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7c19fc9f6df5401bb5c66e1c1807f9a4
CC(C)(C)OC(=O)NCCO.CC(C)c1ccc(CNc2ncccc2C(=O)Nc2ccc(Cl)cc2)c(O)c1>>CC(C)c1ccc(CNc2ncccc2C(=O)Nc2ccc(Cl)cc2)c(OCCNC(=O)OC(C)(C)C)c1
ClC1=CC=C(C=C1)NC(=O)C=1C(=NC=CC1)NCC1=C(C=C(C=C1)C(C)C)O.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C(=O)(OC(C)(C)C)NCCO.N(=NC(=O)OCC)C(=O)OCC>>C(=O)(OC(C)(C)C)NCCOC1=C(CNC2=NC=CC=C2C(=O)NC2=CC=C(C=C2)Cl)C=CC(=C1)C(C)C
[OH:27][CH2:28][CH2:29][NH:30][C:31](=[O:32])[O:33][C:34]([CH3:35])([CH3:36])[CH3:37].O[c:26]1[c:7]([CH2:8][NH:9][c:10]2[n:11][cH:12][cH:13][cH:14][c:15]2[C:16](=[O:17])[NH:18][c:19]2[cH:20][cH:21][c:22]([Cl:23])[cH:24][cH:25]2)[cH:6][cH:5][c:4]([CH:2]([CH3:1])[CH3:3])[cH:38]1>>[CH3:1][CH:2]([CH3:3])[c:4]1[cH:5][cH:6][...
CC(C)(C)OC(=O)NCCO.CC(C)c1ccc(CNc2ncccc2C(=O)Nc2ccc(Cl)cc2)c(O)c1
CC(C)c1ccc(CNc2ncccc2C(=O)Nc2ccc(Cl)cc2)c(OCCNC(=O)OC(C)(C)C)c1
null
null
O1CCCC1
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
8915084acbaaf997bf0f89ff5187cb2f89c25dc683fffc57b3391298c8430dd9
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
O=C(Nc1ccccc1)c1cccnc1NCc1ccccc1
O-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[C:5]):[c:6].[C:7]-[C:8]-[OH;D1;+0:9]>>[C:7]-[C:8]-[O;H0;D2;+0:9]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[C:5]):[c:6]
33.7
[{"value": 30.0, "product": "C(=O)(OC(C)(C)C)NCCOC1=C(CNC2=NC=CC=C2C(=O)NC2=CC=C(C=C2)Cl)C=CC(=C1)C(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 33.7, "product": "C(=O)(OC(C)(C)C)NCCOC1=C(CNC2=NC=CC=C2C(=O)NC2=CC=C(C=C2)Cl)C=CC(=C1)C(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
DAY
To a solution of N-(4-chlorophenyl)-2-[2-hydroxy-4-isopropylbenzylamino]pyridine-3-carboxamide (0.050 g, 0.13 mmol), triphenylphosphine (0.033 g, 0.13 mmol) and N-Boc-ethanolamine (0.018 mg, 0.11 mmol) in 0.3 mL tetrahydrofuran at −10° C. was added a solution of diethyl azodicarboxylate (0.02 mL, 0.13 mmol) in 0.3 mL t...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
c1ccccc1
c1ccccc1
c1ccccc1.c1ccncc1.c1ccccc1
HO-
O1CCCC1
null
72
CC(C)(C)OC(=O)NCCO.CC(C)c1ccc(CNc2ncccc2C(=O)Nc2ccc(Cl)cc2)c(O)c1>O1CCCC1>CC(C)c1ccc(CNc2ncccc2C(=O)Nc2ccc(Cl)cc2)c(OCCNC(=O)OC(C)(C)C)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ef4ebcbafe59483fa610a6277a58bc51
CC(C)c1ccc(CNc2ncccc2C(=O)Nc2ccc(Cl)cc2)c(OCCNC(=O)OC(C)(C)C)c1>>CC(C)c1ccc(CNc2ncccc2C(=O)Nc2ccc(Cl)cc2)c(OCCN)c1
C(=O)(OC(C)(C)C)NCCOC1=C(CNC2=NC=CC=C2C(=O)NC2=CC=C(C=C2)Cl)C=CC(=C1)C(C)C.C(Cl)Cl>>NCCOC1=C(CNC2=NC=CC=C2C(=O)NC2=CC=C(C=C2)Cl)C=CC(=C1)C(C)C
CC(C)(C)OC(=O)[NH:30][CH2:29][CH2:28][O:27][c:26]1[c:7]([CH2:8][NH:9][c:10]2[n:11][cH:12][cH:13][cH:14][c:15]2[C:16](=[O:17])[NH:18][c:19]2[cH:20][cH:21][c:22]([Cl:23])[cH:24][cH:25]2)[cH:6][cH:5][c:4]([CH:2]([CH3:1])[CH3:3])[cH:31]1>>[CH3:1][CH:2]([CH3:3])[c:4]1[cH:5][cH:6][c:7]([CH2:8][NH:9][c:10]2[n:11][cH:12][cH:13...
CC(C)c1ccc(CNc2ncccc2C(=O)Nc2ccc(Cl)cc2)c(OCCNC(=O)OC(C)(C)C)c1
CC(C)c1ccc(CNc2ncccc2C(=O)Nc2ccc(Cl)cc2)c(OCCN)c1
null
null
FC(C(=O)O)(F)F
Reduction
Hydrogenolysis of amides/imides/carbamates
3c33dd2a2d355ee5ba0287367e209aa147a39aa00607f0c95fb2bf1ade45d014
c5b5dffe7dd8beebdc1baa8b5b05300a9f7079e65dcfd42ade6f8a77ff09537d
O=C(Nc1ccccc1)c1cccnc1NCc1ccccc1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2]-[C:3]>>[C:3]-[C:2]-[NH2;D1;+0:1]
88
[{"value": 88.0, "product": "NCCOC1=C(CNC2=NC=CC=C2C(=O)NC2=CC=C(C=C2)Cl)C=CC(=C1)C(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 79.7, "product": "NCCOC1=C(CNC2=NC=CC=C2C(=O)NC2=CC=C(C=C2)Cl)C=CC(=C1)C(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
2-[2-(N-Boc-Aminoethoxy)-4-isopropylbenzylamino]-N-(4-chlorophenyl)pyridine-3-carboxamide (0.02 g, 0.04 mmol) was dissolved in 2 mL of a 1:3 mixture of trifluoroacetic aicd:methylene chloride. The reaction mixture was stirred at room temperature for 30 min. The solvent was removed, and the material was purified by ion ...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Primary amine
null
null
c1ccccc1.c1ccncc1.c1ccccc1
HO-
FC(C(=O)O)(F)F
null
0.5
CC(C)c1ccc(CNc2ncccc2C(=O)Nc2ccc(Cl)cc2)c(OCCNC(=O)OC(C)(C)C)c1>FC(C(=O)O)(F)F>CC(C)c1ccc(CNc2ncccc2C(=O)Nc2ccc(Cl)cc2)c(OCCN)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5347db7719614c68834cfe16e6710679
CC(C)(C)OC(=O)Nc1ccncc1C(=O)O.C[Si](C)(C)C=[N+]=[N-]>>COC(=O)c1cnccc1NC(=O)OC(C)(C)C
C(=O)(OC(C)(C)C)NC1=C(C=NC=C1)C(=O)O.C(C)(=O)O.C[Si](C)(C)C=[N+]=[N-]>>C(=O)(OC(C)(C)C)NC1=C(C=NC=C1)C(=O)OC
[OH:2][C:3](=[O:4])[c:5]1[cH:6][n:7][cH:8][cH:9][c:10]1[NH:11][C:12](=[O:13])[O:14][C:15]([CH3:16])([CH3:17])[CH3:18].C[Si](C)(C)[CH:1]=[N+]=[N-]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][n:7][cH:8][cH:9][c:10]1[NH:11][C:12](=[O:13])[O:14][C:15]([CH3:16])([CH3:17])[CH3:18]
CC(C)(C)OC(=O)Nc1ccncc1C(=O)O.C[Si](C)(C)C=[N+]=[N-]
COC(=O)c1cnccc1NC(=O)OC(C)(C)C
null
null
CO
Heteroatom Alkylation and Arylation
O-alkylation of carboxylic acids with diazo compounds
39589be0e9a30df66714fe618d22a8ac0fb24901dbf2ead1ab33e31556c7ac64
8b539baf7aeb5ab868833e33306bad77200a853d562904197e13de2e27e229d7
c1ccncc1
C-[Si](-C)(-C)-[CH;D2;+0:1]=[N+]=[N-].[#7;a:2]:[c:3]:[c:4]-[C:5](=[O;D1;H0:6])-[OH;D1;+0:7]>>[#7;a:2]:[c:3]:[c:4]-[C:5](=[O;D1;H0:6])-[O;H0;D2;+0:7]-[CH3;D1;+0:1]
81
[{"value": 81.0, "product": "C(=O)(OC(C)(C)C)NC1=C(C=NC=C1)C(=O)OC", "details": "PERCENTYIELD", "is_desired": false}]
null
null
15
MINUTE
To a stirring suspension of 4-(Boc-amino)pyridine-3-carboxylic acid (1.04 g, 4.37 mmol) in methanol (3.5 mL) was added a 2 M solution of (trimethylsilyl)diazomethane in hexanes (3.5 mL, 7 mmol). After 15 min, acetic acid was added and the solvents were removed in vacuo. The residue was chromatographed over silica gel, ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Diazo.Silyl protective group
Ester
null
null
c1ccncc1
Other
CO
null
0.25
CC(C)(C)OC(=O)Nc1ccncc1C(=O)O.C[Si](C)(C)C=[N+]=[N-]>CO>COC(=O)c1cnccc1NC(=O)OC(C)(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d0a6f6a08c924be985b821db55aa71fe
COC(=O)c1cnccc1NC(=O)OC(C)(C)C>>COC(=O)c1cnccc1N
C(=O)(OC(C)(C)C)NC1=C(C=NC=C1)C(=O)OC>>NC1=C(C=NC=C1)C(=O)OC
CC(C)(C)OC(=O)[NH:11][c:10]1[c:5]([C:3]([O:2][CH3:1])=[O:4])[cH:6][n:7][cH:8][cH:9]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][n:7][cH:8][cH:9][c:10]1[NH2:11]
COC(=O)c1cnccc1NC(=O)OC(C)(C)C
COC(=O)c1cnccc1N
null
null
C(=O)(C(F)(F)F)O
Reduction
Hydrogenolysis of amides/imides/carbamates
3c33dd2a2d355ee5ba0287367e209aa147a39aa00607f0c95fb2bf1ade45d014
c5b5dffe7dd8beebdc1baa8b5b05300a9f7079e65dcfd42ade6f8a77ff09537d
c1ccncc1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[c:2]1:[c:3]:[c:4]:[#7;a:5]:[c:6]:[c:7]:1-[C:8](-[#8:9])=[O;D1;H0:10]>>[#8:9]-[C:8](=[O;D1;H0:10])-[c:7]1:[c:6]:[#7;a:5]:[c:4]:[c:3]:[c:2]:1-[NH2;D1;+0:1]
92.8
[{"value": 92.0, "product": "NC1=C(C=NC=C1)C(=O)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 92.8, "product": "NC1=C(C=NC=C1)C(=O)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
45
MINUTE
Methyl 4-(Boc-amino)pyridine-3-carboxylate (2.38 g, 9.4 mmol) was dissolved in TFA (20 mL) and the solution was allowed to stir for 45 min. The solvent was removed in vacuo and the residue was partitioned between 25% isopropanol in chloroform and satd aq sodium bicarbonate. The layers were separated and the aqueous pha...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Primary amine
null
null
c1ccncc1
HO-
C(=O)(C(F)(F)F)O
null
0.75
COC(=O)c1cnccc1NC(=O)OC(C)(C)C>C(=O)(C(F)(F)F)O>COC(=O)c1cnccc1N
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a4e122a776584622b446483b34fbc154
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)Cl)CC1.COC(=O)c1cnccc1N>>COC(=O)C1C=NC=CC1(NC(=O)c1ccccc1OC1CCN(C(=O)OC(C)(C)C)CC1)C(C)(C)C
NC1=C(C=NC=C1)C(=O)OC.ClCCl.C(C)(C)(C)C1=CC(=C(C(=O)Cl)C=C1)OC1CCN(CC1)C(=O)OC(C)(C)C.ClCCl.C(C)(C)N(C(C)C)CC>>C(C)(C)(C)C1(C(C=NC=C1)C(=O)OC)NC(C1=C(C=CC=C1)OC1CCN(CC1)C(=O)OC(C)(C)C)=O
Cl[C:12](=[O:13])[c:14]1[cH:15][cH:16][c:17]([C:34]([CH3:35])([CH3:36])[CH3:37])[cH:18][c:19]1[O:20][CH:21]1[CH2:22][CH2:23][N:24]([C:25](=[O:26])[O:27][C:28]([CH3:29])([CH3:30])[CH3:31])[CH2:32][CH2:33]1.[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][n:7][cH:8][cH:9][c:10]1[NH2:11]>>[CH3:1][O:2][C:3](=[O:4])[CH:5]1[CH:6]=[N:7]...
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)Cl)CC1.COC(=O)c1cnccc1N
COC(=O)C1C=NC=CC1(NC(=O)c1ccccc1OC1CCN(C(=O)OC(C)(C)C)CC1)C(C)(C)C
null
null
C(C)(=O)OCC
Acylation
OtherReaction
4c40b4ac63ec434db0260e5e5e943e6184513743d3104c45e0ac97b2ecf8559b
1fc2dd1a0c8f81d359eaece097d5f07348b604afb79f3effe317cf29392ea335
O=C(NC1C=CN=CC1)c1ccccc1OC1CCNCC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3]1:[c:4]:[c:5]:[c;H0;D3;+0:6](-[C;H0;D4;+0:7](-[C;D1;H3:8])(-[C;D1;H3:9])-[C;D1;H3:10]):[c:11]:[c:12]:1.[C;D1;H3:13]-[#8:14]-[C:15](=[O;D1;H0:16])-[c;H0;D3;+0:17]1:[cH;D2;+0:18]:[n;H0;D2;+0:19]:[cH;D2;+0:20]:[cH;D2;+0:21]:[c;H0;D3;+0:22]:1-[NH2;D1;+0:23]>>[C;D1;H3:13]-[#8:14]-[C:15](...
66
[{"value": 66.0, "product": "C(C)(C)(C)C1(C(C=NC=C1)C(=O)OC)NC(C1=C(C=CC=C1)OC1CCN(CC1)C(=O)OC(C)(C)C)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
To a stirring suspension of methyl 4-aminopyridine-3-carboxylate (0.10 g, 0.659 mmol) in dichloromethane (1 mL) was added a solution of 4-tert-butyl-2-(1-Boc-piperidin-4-yloxy)benzoyl chloride (1.3 mmol) in dichloromethane (6 mL), followed by N,N-diisopropylethylamine (0.15 mL, 0.8 mmol) and 4-N,N-dimethylaminopyridine...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Ester.Primary amine
Ester.Substituted imine.Secondary amide
c1ccccc1.c1ccncc1
C1=CN=CCC1.c1ccccc1
C1=CN=CCC1.c1ccccc1.C1CC[NH]CC1
Other
C(C)(=O)OCC
null
8
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)Cl)CC1.COC(=O)c1cnccc1N>C(C)(=O)OCC>COC(=O)C1C=NC=CC1(NC(=O)c1ccccc1OC1CCN(C(=O)OC(C)(C)C)CC1)C(C)(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7348ba2905634b879e85a0d88faa1132
COC(=O)c1cnccc1NC(=O)c1ccc(C(C)(C)C)cc1OC1CCN(C(=O)OC(C)(C)C)CC1>>CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)Nc2ccncc2C(=O)O)CC1
[Li+].[OH-].C(C)(C)(C)C1=CC(=C(C(=O)NC2=C(C=NC=C2)C(=O)OC)C=C1)OC1CCN(CC1)C(=O)OC(C)(C)C.O.O>>C(C)(C)(C)C1=CC(=C(C(=O)NC2=C(C=NC=C2)C(=O)O)C=C1)OC1CCN(CC1)C(=O)OC(C)(C)C
C[O:34][C:32]([c:31]1[c:26]([NH:25][C:23]([c:22]2[c:13]([O:12][CH:11]3[CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:36][CH2:35]3)[cH:14][c:15]([C:16]([CH3:17])([CH3:18])[CH3:19])[cH:20][cH:21]2)=[O:24])[cH:27][cH:28][n:29][cH:30]1)=[O:33]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:...
COC(=O)c1cnccc1NC(=O)c1ccc(C(C)(C)C)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)Nc2ccncc2C(=O)O)CC1
null
null
O1CCCC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(Nc1ccncc1)c1ccccc1OC1CCNCC1
C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1]
80.2
[{"value": 80.0, "product": "C(C)(C)(C)C1=CC(=C(C(=O)NC2=C(C=NC=C2)C(=O)O)C=C1)OC1CCN(CC1)C(=O)OC(C)(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 80.2, "product": "C(C)(C)(C)C1=CC(=C(C(=O)NC2=C(C=NC=C2)C(=O)O)C=C1)OC1CCN(CC1)C(=O)OC(C)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
To a stirring solution of methyl 4-[4-tert-butyl-2-(1-Boc-piperidin-4-yloxy)benzoylamino]pyridine-3-carboxylate (0.192 g, 0.376 mmol) in tetrahydrofuran (4 mL) was added water (1 mL), followed by a 1 M solution of LiOH in water (0.4 mL, 0.4 mmol). After stirring overnight, the solution was partially concentrated in vac...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CC[NH]CC1.c1ccccc1.c1ccncc1
Other
O1CCCC1
null
8
COC(=O)c1cnccc1NC(=O)c1ccc(C(C)(C)C)cc1OC1CCN(C(=O)OC(C)(C)C)CC1>O1CCCC1>CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)Nc2ccncc2C(=O)O)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7f4dfec2d1b249969514a1e3303875f6
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)Nc2ccncc2C(=O)O)CC1>>CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2-c2nc3ccncc3c(=O)o2)CC1
C(C)(C)(C)C1=CC(=C(C(=O)NC2=C(C=NC=C2)C(=O)O)C=C1)OC1CCN(CC1)C(=O)OC(C)(C)C.Cl.CN(CCCN=C=NCC)C>>C(C)(C)(C)C1=CC(=C(C=C1)C=1OC(C2=C(N1)C=CN=C2)=O)OC2CCN(CC2)C(=O)OC(C)(C)C
O[C:31]([c:30]1[c:25]([NH:24][C:23]([c:22]2[c:13]([O:12][CH:11]3[CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:35][CH2:34]3)[cH:14][c:15]([C:16]([CH3:17])([CH3:18])[CH3:19])[cH:20][cH:21]2)=[O:33])[cH:26][cH:27][n:28][cH:29]1)=[O:32]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH...
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)Nc2ccncc2C(=O)O)CC1
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2-c2nc3ccncc3c(=O)o2)CC1
null
null
CN(C)C=O
Aromatic Heterocycle Formation
OtherReaction
738fce1d0eb6fbbeb524f3efb6a269aaeb4cc42e45f8c3095f069eaec363b8f9
c386cc4dfdcb50b87b14b7a3d3e77ff2ca728c923e8c9b97ba53184613a52138
O=c1oc(-c2ccccc2OC2CCNCC2)nc2ccncc12
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3]1:[c:4]:[#7;a:5]:[c:6]:[c:7]:[c:8]:1-[NH;D2;+0:9]-[C;H0;D3;+0:10](=[O;H0;D1;+0:11])-[c;H0;D3;+0:12](:[c:13]:[c:14]):[c:15](-[#8:16]):[c:17]>>[#8:16]-[c:15](:[c:17]):[c;H0;D3;+0:12](-[c;H0;D3;+0:10]1:[n;H0;D2;+0:9]:[c:8]2:[c:7]:[c:6]:[#7;a:5]:[c:4]:[c:3]:2:[c;H0;D3;+0:1](=[O;D1;H0:2])...
84.1
[{"value": 84.0, "product": "C(C)(C)(C)C1=CC(=C(C=C1)C=1OC(C2=C(N1)C=CN=C2)=O)OC2CCN(CC2)C(=O)OC(C)(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 84.1, "product": "C(C)(C)(C)C1=CC(=C(C=C1)C=1OC(C2=C(N1)C=CN=C2)=O)OC2CCN(CC2)C(=O)OC(C)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
To a stirring solution of 4-[4-tert-butyl-2-(1-Boc-piperidin-4-yloxy)benzoylamino]pyridine-3-carboxylic acid (0.15 g, 0.30 mmol) in DMF (5 mL) was added 1-[3-(dimethyl-amino)propyl]-3-ethylcarbodiimide hydrochloride (0.077 g, 0.39 mmol). After stirring overnight, the solvent was removed in vacuo and the residue was dis...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amide
null
c1ccncc1
c1nc2ccncc2co1
C1CC[NH]CC1.c1ccccc1.c1nc2ccncc2co1
HO-
CN(C)C=O
null
8
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)Nc2ccncc2C(=O)O)CC1>CN(C)C=O>CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2-c2nc3ccncc3c(=O)o2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-537320c1c2dc45428e4e3c3c3aaf4570
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2-c2nc3ccncc3c(=O)o2)CC1.Nc1ccc(Cl)cn1>>CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)Nc2ccncc2C(=O)Nc2ccc(Cl)cn2)CC1
NC1=NC=C(C=C1)Cl.C(C=C)[Mg]Cl.C(C)OCC.C(C)(C)(C)C1=CC(=C(C=C1)C=1OC(C2=C(N1)C=CN=C2)=O)OC2CCN(CC2)C(=O)OC(C)(C)C>>C(C)(C)(C)C1=CC(=C(C(=O)NC2=C(C=NC=C2)C(=O)NC2=NC=C(C=C2)Cl)C=C1)OC1CCN(CC1)C(=O)OC(C)(C)C
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH:11]([O:12][c:13]2[cH:14][c:15]([C:16]([CH3:17])([CH3:18])[CH3:19])[cH:20][cH:21][c:22]2-[c:23]2[o:24][c:32](=[O:33])[c:31]3[c:26]([n:25]2)[cH:27][cH:28][n:29][cH:30]3)[CH2:42][CH2:43]1.[NH2:34][c:35]1[cH:36][cH:37][c:38]([Cl:39])[cH:40][n:41]1>>[C...
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2-c2nc3ccncc3c(=O)o2)CC1.Nc1ccc(Cl)cn1
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)Nc2ccncc2C(=O)Nc2ccc(Cl)cn2)CC1
null
null
C(C)(=O)OCC.C1CCOC1
Acylation
OtherReaction
01ef3ffd9dff64029b5e0e405490bcd195aa6c4c4b93124f80514842cfaec36a
4accd3f274dad8ca7d44350b7d7da15181b5e5579c068528178b23416d2aea4a
O=C(Nc1ccccn1)c1cnccc1NC(=O)c1ccccc1OC1CCNCC1
[#8:1]-[c:2](:[c:3]):[c;H0;D3;+0:4](-[c;H0;D3;+0:5]1:[n;H0;D2;+0:6]:[c:7]2:[c:8]:[c:9]:[#7;a:10]:[c:11]:[c:12]:2:[c;H0;D3;+0:13](=[O;D1;H0:14]):[o;H0;D2;+0:15]:1):[c:16]:[c:17].[NH2;D1;+0:18]-[c:19](:[c:20]):[#7;a:21]:[c:22]>>[#8:1]-[c:2](:[c:3]):[c;H0;D3;+0:4](-[C;H0;D3;+0:5](=[O;H0;D1;+0:15])-[NH;D2;+0:6]-[c:7]1:[c:8...
72.4
[{"value": 70.0, "product": "C(C)(C)(C)C1=CC(=C(C(=O)NC2=C(C=NC=C2)C(=O)NC2=NC=C(C=C2)Cl)C=C1)OC1CCN(CC1)C(=O)OC(C)(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 72.4, "product": "C(C)(C)(C)C1=CC(=C(C(=O)NC2=C(C=NC=C2)C(=O)NC2=NC=C(C=C2)Cl)C=C1)OC1CCN(CC1)C(=O)OC(C)(C)C", "details": "CALCULATEDPERCEN...
null
null
null
null
To a stirring solution of 2-amino-5-chloropyridine (0.055 g, 0.42 mmol) in THF (5 mL) at 0° C., was added a 1.0 M solution of allylmagnesium chloride in diethyl ether (0.4 mL, 0.4 mmol). To this solution was then added a solution of 2-[4-tert-butyl-2-(1-Boc-piperidin-4-yloxy)-phenyl]-4H-pyrido[4,3-d][1,3]oxazin-4-one (...
10.6084/m9.figshare.5104873.v1
null
Primary amine
Secondary amide.Secondary amide
c1nc2ccncc2co1
c1ccncc1
C1CC[NH]CC1.c1ccccc1.c1ccncc1.c1ccncc1
null
C(C)(=O)OCC.C1CCOC1
null
null
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2-c2nc3ccncc3c(=O)o2)CC1.Nc1ccc(Cl)cn1>C(C)(=O)OCC.C1CCOC1>CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)Nc2ccncc2C(=O)Nc2ccc(Cl)cn2)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3f80ed626d8348359710fe0cba5b3db1
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)Nc2ccncc2C(=O)Nc2ccc(Cl)cn2)CC1>>CC(C)(C)c1ccc(C(=O)Nc2ccncc2C(=O)Nc2ccc(Cl)cn2)c(OC2CCNCC2)c1
C(C)(C)(C)C1=CC(=C(C(=O)NC2=C(C=NC=C2)C(=O)NC2=NC=C(C=C2)Cl)C=C1)OC1CCN(CC1)C(=O)OC(C)(C)C.C1(=CC=CC=C1)OC.C(=O)(C(F)(F)F)O>>FC(C(=O)O)(F)F.C(C)(C)(C)C1=CC(=C(C(=O)NC2=C(C=NC=C2)C(=O)NC2=NC=C(C=C2)Cl)C=C1)OC1CCNCC1
CC(C)(C)OC(=O)[N:33]1[CH2:32][CH2:31][CH:30]([O:29][c:28]2[c:8]([C:9](=[O:10])[NH:11][c:12]3[cH:13][cH:14][n:15][cH:16][c:17]3[C:18](=[O:19])[NH:20][c:21]3[cH:22][cH:23][c:24]([Cl:25])[cH:26][n:27]3)[cH:7][cH:6][c:5]([C:2]([CH3:1])([CH3:3])[CH3:4])[cH:36]2)[CH2:35][CH2:34]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[c:5]1[cH:6][c...
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)Nc2ccncc2C(=O)Nc2ccc(Cl)cn2)CC1
CC(C)(C)c1ccc(C(=O)Nc2ccncc2C(=O)Nc2ccc(Cl)cn2)c(OC2CCNCC2)c1
null
null
ClCCl
Reduction
Boc amine deprotection
bf3cd5dc3e17e694d8665c89f5d7e08e8763b18436a633eb66e9bf530b8b0316
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
O=C(Nc1ccccn1)c1cnccc1NC(=O)c1ccccc1OC1CCNCC1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1](-[C:2]-[C:3])-[C:4]-[C:5]>>[C:3]-[C:2]-[NH;D2;+0:1]-[C:4]-[C:5]
88
[{"value": 88.0, "product": "FC(C(=O)O)(F)F.C(C)(C)(C)C1=CC(=C(C(=O)NC2=C(C=NC=C2)C(=O)NC2=NC=C(C=C2)Cl)C=C1)OC1CCNCC1", "details": "PERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
To a stirring solution of 4-[4-tert-butyl-2-(1-Boc-piperidin-4-yloxy)benzoylamino]-N-(5-chloropyridin-2-yl)pyridine-3-carboxamide (0.099 g, 0.163 mmol) and anisole (0.1 mL) in dichloromethane (5 mL) was added TFA (0.5 mL). After 2 h, the solvent was removed in vacuo and the residue was suspended in toluene and concentr...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
C1CC[NH]CC1
C1CCNCC1
c1ccccc1.c1ccncc1.c1ccncc1.C1CCNCC1
HO-
ClCCl
null
2
CC(C)(C)OC(=O)N1CCC(Oc2cc(C(C)(C)C)ccc2C(=O)Nc2ccncc2C(=O)Nc2ccc(Cl)cn2)CC1>ClCCl>CC(C)(C)c1ccc(C(=O)Nc2ccncc2C(=O)Nc2ccc(Cl)cn2)c(OC2CCNCC2)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2eff0da841654459882383e7c9b1b5c1
COC(=O)c1ccc(O)cc1O.FCCBr>>COC(=O)c1ccc(OCCF)cc1O
OC1=C(C(=O)OC)C=CC(=C1)O.BrCCF.C([O-])([O-])=O.[K+].[K+].[I-].[K+]>>FCCOC1=CC(=C(C(=O)OC)C=C1)O
[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([OH:9])[cH:13][c:14]1[OH:15].Br[CH2:10][CH2:11][F:12]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([O:9][CH2:10][CH2:11][F:12])[cH:13][c:14]1[OH:15]
COC(=O)c1ccc(O)cc1O.FCCBr
COC(=O)c1ccc(OCCF)cc1O
null
null
O.CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
c1ccccc1
Br-[CH2;D2;+0:1]-[C:2]-[F;D1;H0:3].[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[F;D1;H0:3]-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]
null
[]
57.5
CELSIUS
null
null
A mixture of methyl 2,4-dihydroxybenzoate (5.04 g, 30 mmol), 1-bromo-2-fluoroethane (4.18 g, 2.46 mL, 33 mmol), potassium carbonate (4.55 g, 33 mmol) and potassium iodide (1 g) in DMF (20 mL) was heated overnight at 55-60° C. before it was poured into water (150 mL). The resulting white precipitate was filtered, rediss...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1
HBr
O.CN(C)C=O
57.5
null
COC(=O)c1ccc(O)cc1O.FCCBr>O.CN(C)C=O>COC(=O)c1ccc(OCCF)cc1O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-124911f9618c472dbe489aba7f243e43
CC(C)(C)OC(=O)N1CCC(O)CC1.COC(=O)c1ccc(OCCF)cc1O>>COC(=O)c1ccc(OCCF)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
FCCOC1=CC(=C(C(=O)OC)C=C1)O.C(C)(C)(C)OC(=O)N1CCC(CC1)O.N(=NC(=O)OCC)C(=O)OCC.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1>>C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)OC)C=CC(=C1)OCCF
O[CH:16]1[CH2:17][CH2:18][N:19]([C:20](=[O:21])[O:22][C:23]([CH3:24])([CH3:25])[CH3:26])[CH2:27][CH2:28]1.[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([O:9][CH2:10][CH2:11][F:12])[cH:13][c:14]1[OH:15]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([O:9][CH2:10][CH2:11][F:12])[cH:13][c:14]1[O:15][CH:16]1[CH2:17][...
CC(C)(C)OC(=O)N1CCC(O)CC1.COC(=O)c1ccc(OCCF)cc1O
COC(=O)c1ccc(OCCF)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
a9e936b0e9135225700edbab1c7696738b7f1f0756494b6ceeeda63b184d572f
776ba735002e33225fbc578943016110c2c43efefd97bfeea4ec3cc2e2e1532f
c1ccc(OC2CCNCC2)cc1
O-[CH;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1.[#8:7]-[C:8](=[O;D1;H0:9])-[c:10]:[c:11](-[OH;D1;+0:12]):[c:13]>>[#8:7]-[C:8](=[O;D1;H0:9])-[c:10]:[c:11](-[O;H0;D2;+0:12]-[CH;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1):[c:13]
102.9
[{"value": 102.9, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)OC)C=CC(=C1)OCCF", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using a procedure similar to that of Example 6-D, methyl 4-(2-fluoroethoxy)-2-hydroxybenzoate (3.6 g, 17.8 mmol), 1-tert-butoxycarbonyl-4-hydroxypiperidine (3.58 g, 17.8 mmol), and triphenylphosphine (5.60 g, 21.4 mmol) in THF (75 mL) is treated with diethyl azodicarboxylate (3.60 g, 17.8 mmol) in THF (15 mL) to afford...
10.6084/m9.figshare.5104873.v1
null
Secondary alcohol.Aromatic alcohol
Ether
C1CC[NH]CC1
C1CC[NH]CC1
c1ccccc1.C1CC[NH]CC1
HO-
C1CCOC1
null
null
CC(C)(C)OC(=O)N1CCC(O)CC1.COC(=O)c1ccc(OCCF)cc1O>C1CCOC1>COC(=O)c1ccc(OCCF)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-648d187d3a16427b93e0cce86473ba35
COC(=O)c1ccc(OCCF)cc1OC1CCN(C(=O)OC(C)(C)C)CC1>>CC(C)(C)OC(=O)N1CCC(Oc2cc(OCCF)ccc2C(=O)O)CC1
C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)OC)C=CC(=C1)OCCF.O[Li].O.O>>C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)O)C=CC(=C1)OCCF
C[O:25][C:23]([c:22]1[c:13]([O:12][CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:27][CH2:26]2)[cH:14][c:15]([O:16][CH2:17][CH2:18][F:19])[cH:20][cH:21]1)=[O:24]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH:11]([O:12][c:13]2[cH:14][c:15]([O:16][CH2:17][CH2...
COC(=O)c1ccc(OCCF)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
CC(C)(C)OC(=O)N1CCC(Oc2cc(OCCF)ccc2C(=O)O)CC1
null
null
C1CCOC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(OC2CCNCC2)cc1
C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]>>[O;D1;H0:3]=[C:2](-[OH;D1;+0:1])-[c:4]
40
[{"value": 40.0, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)O)C=CC(=C1)OCCF", "details": "PERCENTYIELD", "is_desired": false}, {"value": 39.3, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)O)C=CC(=C1)OCCF", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using a procedure similar to that of Example 6-E, methyl 2-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-(2-fluoroethoxy)benzoate (7.28 g) is hydrolyzed using LiOH.H2O (1.78 g, 2.2 equivalents), water (20 mL) and THF (60 mL) at 60-65° C. to afford the acid (2.76 g, 40%). Conditions: See reaction.notes.procedure_details. W...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CC[NH]CC1.c1ccccc1
Other
C1CCOC1
null
null
COC(=O)c1ccc(OCCF)cc1OC1CCN(C(=O)OC(C)(C)C)CC1>C1CCOC1>CC(C)(C)OC(=O)N1CCC(Oc2cc(OCCF)ccc2C(=O)O)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-445ff504caa7472293b9a6f54b4d2ea7
CC(C)(C)OC(=O)N1CCCC(CO)C1.CCOC(=O)N=NC(=O)OCC.O=C([O-])c1ccc(OCCF)cc1O>>COC(=O)c1ccc(OCCF)cc1OCC1CCCN(C(=O)OC(C)(C)C)C1
FCCOC1=CC(=C(C(=O)[O-])C=C1)O.C(C)(C)(C)OC(=O)N1CC(CCC1)CO.N(=NC(=O)OCC)C(=O)OCC.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1>>C(C)(C)(C)OC(=O)N1CC(CCC1)COC1=C(C(=O)OC)C=CC(=C1)OCCF
O[CH2:16][CH:17]1[CH2:18][CH2:19][CH2:20][N:21]([C:22](=[O:23])[O:24][C:25]([CH3:26])([CH3:27])[CH3:28])[CH2:29]1.CCOC(=O)N=NC(=O)O[CH2:1]C.[O-:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([O:9][CH2:10][CH2:11][F:12])[cH:13][c:14]1[OH:15]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([O:9][CH2:10][CH2:11][F:12])[cH:13][c...
CC(C)(C)OC(=O)N1CCCC(CO)C1.CCOC(=O)N=NC(=O)OCC.O=C([O-])c1ccc(OCCF)cc1O
COC(=O)c1ccc(OCCF)cc1OCC1CCCN(C(=O)OC(C)(C)C)C1
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
OtherReaction
6998b76c1fb00648c00a2106cbf23f36aee9db18b229882ac92a6f575220302c
c25afff91d4c1e70d2e5ea98a0decb1c958ecc71eaf896f606fa5564ee4cf400
c1ccc(OCC2CCCNC2)cc1
C-C-O-C(=O)-N=N-C(=O)-O-[CH2;D2;+0:1]-C.O-[CH2;D2;+0:2]-[C:3](-[C:4])-[C:5]-[#7:6].[O-;H0;D1:7]-[C:8](=[O;D1;H0:9])-[c:10]:[c:11](-[OH;D1;+0:12]):[c:13]>>[#7:6]-[C:5]-[C:3](-[CH2;D2;+0:2]-[O;H0;D2;+0:12]-[c:11](:[c:13]):[c:10]-[C:8](=[O;D1;H0:9])-[O;H0;D2;+0:7]-[CH3;D1;+0:1])-[C:4]
120.6
[{"value": 120.6, "product": "C(C)(C)(C)OC(=O)N1CC(CCC1)COC1=C(C(=O)OC)C=CC(=C1)OCCF", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using a procedure similar to that of Example 26-B, 4-(2-fluoroethoxy)-2-hydroxybenzoate (2.6 g, 12.8 mmol), 1-tert-butoxycarbonylpiperidin-3-ylmethanol (2.76 g, 12.8 mmol), and triphenylphosphine (4.02 g, 15.4 mmol) in THF (50 mL) is treated with diethyl azodicarboxylate (2.59 g, 12.8 mmol) in THF to afford methyl 2-(1...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether.Diazene.Primary alcohol.Aromatic alcohol
Ester.Ether
null
null
c1ccccc1.C1CC[NH]CC1
HO-
C1CCOC1
null
null
CC(C)(C)OC(=O)N1CCCC(CO)C1.CCOC(=O)N=NC(=O)OCC.O=C([O-])c1ccc(OCCF)cc1O>C1CCOC1>COC(=O)c1ccc(OCCF)cc1OCC1CCCN(C(=O)OC(C)(C)C)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-02293026a49c475ba7ec60af6f3d7760
COC(=O)c1ccc(OCCF)cc1OCC1CCCN(C(=O)OC(C)(C)C)C1>>CC(C)(C)OC(=O)N1CCCC(COc2cc(OCCF)ccc2C(=O)O)C1
C(C)(C)(C)OC(=O)N1CC(CCC1)COC1=C(C(=O)OC)C=CC(=C1)OCCF.O[Li].O.O>>C(C)(C)(C)OC(=O)N1CC(CCC1)COC1=C(C(=O)O)C=CC(=C1)OCCF
C[O:27][C:25]([c:24]1[c:15]([O:14][CH2:13][CH:12]2[CH2:11][CH2:10][CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:28]2)[cH:16][c:17]([O:18][CH2:19][CH2:20][F:21])[cH:22][cH:23]1)=[O:26]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH2:11][CH:12]([CH2:13][O:14][c:15]2[cH:16][...
COC(=O)c1ccc(OCCF)cc1OCC1CCCN(C(=O)OC(C)(C)C)C1
CC(C)(C)OC(=O)N1CCCC(COc2cc(OCCF)ccc2C(=O)O)C1
null
null
C1CCOC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(OCC2CCCNC2)cc1
C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]>>[O;D1;H0:3]=[C:2](-[OH;D1;+0:1])-[c:4]
null
[]
null
null
null
null
Using a procedure similar to that of Example 26-C, the ester is hydrolyzed using LiOH.H2O (1.50 g, 2.2 equivalents), water (20 mL) and THF (60 mL) to afford the acid (2.93 g, 59% for the two steps). Conditions: See reaction.notes.procedure_details. Workup: to afford the acid (2.93 g, 59% for the two steps)
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CC[NH]CC1.c1ccccc1
Other
C1CCOC1
null
null
COC(=O)c1ccc(OCCF)cc1OCC1CCCN(C(=O)OC(C)(C)C)C1>C1CCOC1>CC(C)(C)OC(=O)N1CCCC(COc2cc(OCCF)ccc2C(=O)O)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3391cfa1a6a840eebbbe1fab055a94af
CC(C)(CO)CNC(=O)OC(C)(C)C.COC(=O)c1ccc(OCCF)cc1O>>COC(=O)c1ccc(OCCF)cc1OCC(C)(C)CNC(=O)OC(C)(C)C
FCCOC1=CC(=C(C(=O)OC)C=C1)O.C(C)(C)(C)OC(=O)NCC(CO)(C)C>>C(C)(C)(C)OC(=O)NCC(COC1=C(C(=O)OC)C=CC(=C1)OCCF)(C)C
O[CH2:16][C:17]([CH3:18])([CH3:19])[CH2:20][NH:21][C:22](=[O:23])[O:24][C:25]([CH3:26])([CH3:27])[CH3:28].[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([O:9][CH2:10][CH2:11][F:12])[cH:13][c:14]1[OH:15]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([O:9][CH2:10][CH2:11][F:12])[cH:13][c:14]1[O:15][CH2:16][C:17]([C...
CC(C)(CO)CNC(=O)OC(C)(C)C.COC(=O)c1ccc(OCCF)cc1O
COC(=O)c1ccc(OCCF)cc1OCC(C)(C)CNC(=O)OC(C)(C)C
null
null
null
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1ccccc1
O-[CH2;D2;+0:1]-[C:2](-[C:3])(-[C;D1;H3:4])-[C;D1;H3:5].[#8:6]-[C:7](=[O;D1;H0:8])-[c:9]:[c:10](-[OH;D1;+0:11]):[c:12]>>[#8:6]-[C:7](=[O;D1;H0:8])-[c:9]:[c:10](-[O;H0;D2;+0:11]-[CH2;D2;+0:1]-[C:2](-[C:3])(-[C;D1;H3:4])-[C;D1;H3:5]):[c:12]
72
[{"value": 72.0, "product": "C(C)(C)(C)OC(=O)NCC(COC1=C(C(=O)OC)C=CC(=C1)OCCF)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using a procedure similar to that of Example 26-B, methyl 4-(2-fluoroethoxy)-2-hydroxybenzoate (3.6 g, 17.8 mmol) is alkylated with 3-tert-butoxycarbonylamino-2,2-dimethylpropanol (3.62 g, 17.8 mmol) to afford methyl 2-(3-tert-butoxycarbonylamino-2,2-dimethylpropoxy)-4-(2-fluoroethoxy)benzoate (5.12 g). Conditions: See...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccccc1
HO-
null
null
null
CC(C)(CO)CNC(=O)OC(C)(C)C.COC(=O)c1ccc(OCCF)cc1O>>COC(=O)c1ccc(OCCF)cc1OCC(C)(C)CNC(=O)OC(C)(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-0fe4a2024130415982a1cf7bb40535a2
CC(C)(C)OC(=O)N[C@@H]1CC[C@@H](O)CC1.COC(=O)c1ccc(OCCF)cc1O>>COC(=O)c1ccc(OCCF)cc1O[C@@H]1CC[C@H](NC(=O)OC(C)(C)C)CC1
FCCOC1=CC(=C(C(=O)OC)C=C1)O.C(C)(C)(C)OC(=O)N[C@@H]1CC[C@H](CC1)O.N(=NC(=O)OCC)C(=O)OCC.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1>>C(C)(C)(C)OC(=O)N[C@H]1CC[C@H](CC1)OC1=C(C(=O)OC)C=CC(=C1)OCCF
[OH:15][C@H:16]1[CH2:17][CH2:18][C@H:19]([NH:20][C:21](=[O:22])[O:23][C:24]([CH3:25])([CH3:26])[CH3:27])[CH2:28][CH2:29]1.O[c:14]1[c:5]([C:3]([O:2][CH3:1])=[O:4])[cH:6][cH:7][c:8]([O:9][CH2:10][CH2:11][F:12])[cH:13]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([O:9][CH2:10][CH2:11][F:12])[cH:13][c:14]1[O:15][C@H:...
CC(C)(C)OC(=O)N[C@@H]1CC[C@@H](O)CC1.COC(=O)c1ccc(OCCF)cc1O
COC(=O)c1ccc(OCCF)cc1O[C@@H]1CC[C@H](NC(=O)OC(C)(C)C)CC1
null
null
CCCCCC.C(C)(=O)OCC.C1CCOC1
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
de817abd28aa0a6201a692784d613d548e53f67c49ed49b6eff382c8e9e7a9e4
776ba735002e33225fbc578943016110c2c43efefd97bfeea4ec3cc2e2e1532f
c1ccc(OC2CCCCC2)cc1
O-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[C:5](=[O;D1;H0:6])-[#8:7]-[C;D1;H3:8]):[c:9].[C:10]-[C:11](-[OH;D1;+0:12])-[C:13]>>[C:10]-[C:11](-[O;H0;D2;+0:12]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[C:5](=[O;D1;H0:6])-[#8:7]-[C;D1;H3:8]):[c:9])-[C:13]
71.7
[{"value": 71.7, "product": "C(C)(C)(C)OC(=O)N[C@H]1CC[C@H](CC1)OC1=C(C(=O)OC)C=CC(=C1)OCCF", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
Using a procedure similar to that of Example 6-D, methyl 4-(2-fluoroethoxy)-2-hydroxybenzoate (5.0 g, 24.75 mmol), trans-4-tert-butoxycarbonylaminocyclohexanol (5.02 g, 24.75 mmol), and triphenylphosphine (1.2 equivalents) in THF (125 mL) is treated with diethyl azodicarboxylate (1.3 equivalents) in THF (25 mL). After ...
10.6084/m9.figshare.5104873.v1
null
Secondary alcohol.Aromatic alcohol
Ether
c1ccccc1
c1ccccc1
c1ccccc1.C1CCCCC1
HO-
CCCCCC.C(C)(=O)OCC.C1CCOC1
null
8
CC(C)(C)OC(=O)N[C@@H]1CC[C@@H](O)CC1.COC(=O)c1ccc(OCCF)cc1O>CCCCCC.C(C)(=O)OCC.C1CCOC1>COC(=O)c1ccc(OCCF)cc1O[C@@H]1CC[C@H](NC(=O)OC(C)(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a02efbc475594085be6d4557b60f84e4
CC(C)(C)OC(=O)N1CCC(O)CC1.COC(=O)c1ccc(OCC(F)(F)F)cc1O>>COC(=O)c1ccc(OCC(F)(F)F)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
OC1=C(C(=O)OC)C=CC(=C1)OCC(F)(F)F.C(C)(C)(C)OC(=O)N1CCC(CC1)O>>C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)OC)C=CC(=C1)OCC(F)(F)F
O[CH:18]1[CH2:19][CH2:20][N:21]([C:22](=[O:23])[O:24][C:25]([CH3:26])([CH3:27])[CH3:28])[CH2:29][CH2:30]1.[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([O:9][CH2:10][C:11]([F:12])([F:13])[F:14])[cH:15][c:16]1[OH:17]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([O:9][CH2:10][C:11]([F:12])([F:13])[F:14])[cH:15][c...
CC(C)(C)OC(=O)N1CCC(O)CC1.COC(=O)c1ccc(OCC(F)(F)F)cc1O
COC(=O)c1ccc(OCC(F)(F)F)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
null
null
null
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
a9e936b0e9135225700edbab1c7696738b7f1f0756494b6ceeeda63b184d572f
776ba735002e33225fbc578943016110c2c43efefd97bfeea4ec3cc2e2e1532f
c1ccc(OC2CCNCC2)cc1
O-[CH;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1.[#8:7]-[C:8](=[O;D1;H0:9])-[c:10]:[c:11](-[OH;D1;+0:12]):[c:13]>>[#8:7]-[C:8](=[O;D1;H0:9])-[c:10]:[c:11](-[O;H0;D2;+0:12]-[CH;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1):[c:13]
82.6
[{"value": 82.6, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)OC)C=CC(=C1)OCC(F)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using a procedure similar to that of Example 26-B, methyl 2-hydroxy-4-(2,2,2-trifluoroethoxy)benzoate (2.0 g, 7.99 mmol) is alkylated with 1-tert-butoxycarbonyl-4-hydroxypiperidine (1.61 g, 7.99 mmol) to afford methyl 2-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-(2,2,2-trifluoroethoxy)benzoate (2.86 g). Conditions: See...
10.6084/m9.figshare.5104873.v1
null
Secondary alcohol.Aromatic alcohol
Ether
C1CC[NH]CC1
C1CC[NH]CC1
c1ccccc1.C1CC[NH]CC1
HO-
null
null
null
CC(C)(C)OC(=O)N1CCC(O)CC1.COC(=O)c1ccc(OCC(F)(F)F)cc1O>>COC(=O)c1ccc(OCC(F)(F)F)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-51306b4812214cf79eac7b994c37ae78
COC(=O)c1ccc(O)cc1O.COCCBr>>COCCOc1ccc(C(=O)OC)c(O)c1
OC1=C(C(=O)OC)C=CC(=C1)O.BrCCOC.C([O-])([O-])=O.[K+].[K+].[I-].[Na+]>>OC1=C(C(=O)OC)C=CC(=C1)OCCOC
[OH:5][c:6]1[cH:7][cH:8][c:9]([C:10](=[O:11])[O:12][CH3:13])[c:14]([OH:15])[cH:16]1.Br[CH2:4][CH2:3][O:2][CH3:1]>>[CH3:1][O:2][CH2:3][CH2:4][O:5][c:6]1[cH:7][cH:8][c:9]([C:10](=[O:11])[O:12][CH3:13])[c:14]([OH:15])[cH:16]1
COC(=O)c1ccc(O)cc1O.COCCBr
COCCOc1ccc(C(=O)OC)c(O)c1
null
null
[Cl-].[Na+].O.CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
c1ccccc1
Br-[CH2;D2;+0:1]-[C:2]-[#8:3].[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[#8:3]-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]
null
[]
57.5
CELSIUS
null
null
A mixture of methyl 2,4-dihydroxybenzoate (5.04 g, 30 mmol), 1-bromo-2-methoxyethane (3.1 mL, 33 mmol), potassium carbonate (4.55 g, 33 mmol) and sodium iodide (1 g) in DMF (20 mL) was heated overnight at 55-60° C. before it was poured into brine (300 mL). The resulting mixture was extracted with ethyl acetate; and the...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1
HBr
[Cl-].[Na+].O.CN(C)C=O
57.5
null
COC(=O)c1ccc(O)cc1O.COCCBr>[Cl-].[Na+].O.CN(C)C=O>COCCOc1ccc(C(=O)OC)c(O)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ae2dc634d3044565838c9800d362b386
CC(C)(C)OC(=O)N1CCC(O)CC1.COCCOc1ccc(C(=O)OC)c(O)c1>>COCCOc1ccc(C(=O)OC)c(OC2CCN(C(=O)OC(C)(C)C)CC2)c1
OC1=C(C(=O)OC)C=CC(=C1)OCCOC.C(C)(C)(C)OC(=O)N1CCC(CC1)O>>C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)OC)C=CC(=C1)OCCOC
O[CH:16]1[CH2:17][CH2:18][N:19]([C:20](=[O:21])[O:22][C:23]([CH3:24])([CH3:25])[CH3:26])[CH2:27][CH2:28]1.[CH3:1][O:2][CH2:3][CH2:4][O:5][c:6]1[cH:7][cH:8][c:9]([C:10](=[O:11])[O:12][CH3:13])[c:14]([OH:15])[cH:29]1>>[CH3:1][O:2][CH2:3][CH2:4][O:5][c:6]1[cH:7][cH:8][c:9]([C:10](=[O:11])[O:12][CH3:13])[c:14]([O:15][CH:16...
CC(C)(C)OC(=O)N1CCC(O)CC1.COCCOc1ccc(C(=O)OC)c(O)c1
COCCOc1ccc(C(=O)OC)c(OC2CCN(C(=O)OC(C)(C)C)CC2)c1
null
null
null
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
a9e936b0e9135225700edbab1c7696738b7f1f0756494b6ceeeda63b184d572f
776ba735002e33225fbc578943016110c2c43efefd97bfeea4ec3cc2e2e1532f
c1ccc(OC2CCNCC2)cc1
O-[CH;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1.[#8:7]-[C:8](=[O;D1;H0:9])-[c:10]:[c:11](-[OH;D1;+0:12]):[c:13]>>[#8:7]-[C:8](=[O;D1;H0:9])-[c:10]:[c:11](-[O;H0;D2;+0:12]-[CH;D3;+0:1]1-[C:2]-[C:3]-[#7:4]-[C:5]-[C:6]-1):[c:13]
89.6
[{"value": 89.6, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)OC1=C(C(=O)OC)C=CC(=C1)OCCOC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using a procedure similar to that of Example 26-B, methyl 2-hydroxy-4-(2-methoxyethoxy)benzoate (2.72 g, 12.02 mmol) is alkylated with 1-tert-butoxycarbonyl-4-hydroxy-piperidine (2.44 g, 12.02 mmol) to afford methyl 2-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-(2-methoxyethoxy)benzoate (4.41 g). Conditions: See reactio...
10.6084/m9.figshare.5104873.v1
null
Secondary alcohol.Aromatic alcohol
Ether
C1CC[NH]CC1
C1CC[NH]CC1
c1ccccc1.C1CC[NH]CC1
HO-
null
null
null
CC(C)(C)OC(=O)N1CCC(O)CC1.COCCOc1ccc(C(=O)OC)c(O)c1>>COCCOc1ccc(C(=O)OC)c(OC2CCN(C(=O)OC(C)(C)C)CC2)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c2dc5be7370c4e9b94725db4891a4666
CC(C)(CO)CNC(=O)OC(C)(C)C.COCCOc1ccc(C(=O)OC)c(O)c1>>COCCOc1ccc(C(=O)OC)c(OCC(C)(C)CNC(=O)OC(C)(C)C)c1
OC1=C(C(=O)OC)C=CC(=C1)OCCOC.C(C)(C)(C)OC(=O)NCC(CO)(C)C>>C(C)(C)(C)OC(=O)NCC(COC1=C(C(=O)OC)C=CC(=C1)OCCOC)(C)C
O[CH2:16][C:17]([CH3:18])([CH3:19])[CH2:20][NH:21][C:22](=[O:23])[O:24][C:25]([CH3:26])([CH3:27])[CH3:28].[CH3:1][O:2][CH2:3][CH2:4][O:5][c:6]1[cH:7][cH:8][c:9]([C:10](=[O:11])[O:12][CH3:13])[c:14]([OH:15])[cH:29]1>>[CH3:1][O:2][CH2:3][CH2:4][O:5][c:6]1[cH:7][cH:8][c:9]([C:10](=[O:11])[O:12][CH3:13])[c:14]([O:15][CH2:1...
CC(C)(CO)CNC(=O)OC(C)(C)C.COCCOc1ccc(C(=O)OC)c(O)c1
COCCOc1ccc(C(=O)OC)c(OCC(C)(C)CNC(=O)OC(C)(C)C)c1
null
null
null
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1ccccc1
O-[CH2;D2;+0:1]-[C:2](-[C:3])(-[C;D1;H3:4])-[C;D1;H3:5].[#8:6]-[C:7](=[O;D1;H0:8])-[c:9]:[c:10](-[OH;D1;+0:11]):[c:12]>>[#8:6]-[C:7](=[O;D1;H0:8])-[c:9]:[c:10](-[O;H0;D2;+0:11]-[CH2;D2;+0:1]-[C:2](-[C:3])(-[C;D1;H3:4])-[C;D1;H3:5]):[c:12]
85.6
[{"value": 85.6, "product": "C(C)(C)(C)OC(=O)NCC(COC1=C(C(=O)OC)C=CC(=C1)OCCOC)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using a procedure similar to that of Example 26-B, methyl 2-hydroxy-4-(2-methoxyethoxy)benzoate (3.2 g, 14.14 mmol) is alkylated with 3-tert-butoxycarbonylamino-2,2-dimethylpropanol (2.88 g, 14.14 mmol) to afford methyl 2-(3-tert-butoxycarbonylamino-2,2-dimethylpropoxy)-4-(2-methoxyethoxy)benzoate (4.982 g) after purif...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccccc1
HO-
null
null
null
CC(C)(CO)CNC(=O)OC(C)(C)C.COCCOc1ccc(C(=O)OC)c(O)c1>>COCCOc1ccc(C(=O)OC)c(OCC(C)(C)CNC(=O)OC(C)(C)C)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7fdc48bc0b414ef59a18e4908777305b
COCOc1cccc(C2(C)OCCO2)c1.O=C=O>>COCOc1cc(C2(C)OCCO2)ccc1C(=O)O
C(=O)=O.CC1(OCCO1)C=1C=C(C=CC1)OCOC.C(C)(C)(C)[Li]>>CC1(OCCO1)C1=CC(=C(C(=O)O)C=C1)OCOC
[CH3:1][O:2][CH2:3][O:4][c:5]1[cH:6][c:7]([C:8]2([CH3:9])[O:10][CH2:11][CH2:12][O:13]2)[cH:14][cH:15][cH:16]1.[C:17](=[O:18])=[O:19]>>[CH3:1][O:2][CH2:3][O:4][c:5]1[cH:6][c:7]([C:8]2([CH3:9])[O:10][CH2:11][CH2:12][O:13]2)[cH:14][cH:15][c:16]1[C:17](=[O:18])[OH:19]
COCOc1cccc(C2(C)OCCO2)c1.O=C=O
COCOc1cc(C2(C)OCCO2)ccc1C(=O)O
null
null
CCOCC
Acylation
OtherReaction
d512242205ca0afb7920772ddd09825654068f093b5b2190929ae26db328221a
f2fa2063dd26da08ea200eb6cbb3037b91013a82352a2b60120e98f9e54cbd88
c1ccc(C2OCCO2)cc1
[#8:1]-[c:2](:[c:3]):[cH;D2;+0:4]:[c:5]:[c:6].[O;D1;H0:7]=[C;H0;D2;+0:8]=[O;H0;D1;+0:9]>>[#8:1]-[c:2](:[c:3]):[c;H0;D3;+0:4](-[C;H0;D3;+0:8](=[O;D1;H0:7])-[OH;D1;+0:9]):[c:5]:[c:6]
null
[]
10
CELSIUS
null
null
To a solution of methoxymethyl 3-(2-methyl-1,3-dioxolan-2-yl)phenyl ether (8.16 g, 36.4 mmol) in ether (200 mL) was added dropwise tert-butyl lithium (1.7 M solution, 26.8 mL, 1.25 equivalents) at −5 to −10° C. The reaction mixture was stirred 15 min before carbon dioxide gas was bubbled in for 5 min. The reaction mixt...
10.6084/m9.figshare.5104873.v1
null
Carbon dioxide
Carboxylic acid
c1ccccc1
c1ccccc1
c1ccccc1.C1COCO1
null
CCOCC
10
null
COCOc1cccc(C2(C)OCCO2)c1.O=C=O>CCOCC>COCOc1cc(C2(C)OCCO2)ccc1C(=O)O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-506d020f05dc4e06926c5a703d23fbaa
COCOc1cc(C2(C)OCCO2)ccc1C(=O)Nc1cccnc1C(=O)Nc1ccc(Cl)cn1>>CC(=O)c1ccc(C(=O)Nc2cccnc2C(=O)Nc2ccc(Cl)cn2)c(O)c1
ClC=1C=CC(=NC1)NC(=O)C1=NC=CC=C1NC(C1=C(C=C(C=C1)C1(OCCO1)C)OCOC)=O.C(=O)(C(F)(F)F)O>>C(C)(=O)C1=CC(=C(C(=O)NC=2C(=NC=CC2)C(=O)NC2=NC=C(C=C2)Cl)C=C1)O
COC[O:28][c:27]1[c:7]([C:8](=[O:9])[NH:10][c:11]2[cH:12][cH:13][cH:14][n:15][c:16]2[C:17](=[O:18])[NH:19][c:20]2[cH:21][cH:22][c:23]([Cl:24])[cH:25][n:26]2)[cH:6][cH:5][c:4]([C:2]2([CH3:1])OCC[O:3]2)[cH:29]1>>[CH3:1][C:2](=[O:3])[c:4]1[cH:5][cH:6][c:7]([C:8](=[O:9])[NH:10][c:11]2[cH:12][cH:13][cH:14][n:15][c:16]2[C:17]...
COCOc1cc(C2(C)OCCO2)ccc1C(=O)Nc1cccnc1C(=O)Nc1ccc(Cl)cn1
CC(=O)c1ccc(C(=O)Nc2cccnc2C(=O)Nc2ccc(Cl)cn2)c(O)c1
null
null
O
Miscellaneous
OtherReaction
6c74714319c018934ab052dab2883ec1715618294b3a59459bcb05e410cf5362
3448fc7deb63a7904c2d5aaa772e6ddc22b9edb260ac097cd876b0f3e36979b0
O=C(Nc1cccnc1C(=O)Nc1ccccn1)c1ccccc1
C-O-C-[O;H0;D2;+0:1]-[c:2](:[c:3]:[c:4](-[C;H0;D4;+0:5]1(-[C;D1;H3:6])-O-C-C-[O;H0;D2;+0:7]-1):[c:8]):[c:9]-[C:10](-[#7:11])=[O;D1;H0:12]>>[#7:11]-[C:10](=[O;D1;H0:12])-[c:9]:[c:2](-[OH;D1;+0:1]):[c:3]:[c:4](-[C;H0;D3;+0:5](-[C;D1;H3:6])=[O;H0;D1;+0:7]):[c:8]
18.6
[{"value": 18.6, "product": "C(C)(=O)C1=CC(=C(C(=O)NC=2C(=NC=CC2)C(=O)NC2=NC=C(C=C2)Cl)C=C1)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
N-(5-Chloropyridin-2-yl)-3-[4-(2-methyl-1,3-dioxolan-2-yl)-2-(methoxymethoxy)benzoylamino]pyridine-2-carboxamide (3.10 g) is treated with a solution of TFA (20 mL) and water (20 mL) for 2 h before the solution is evaporated. The residue is slurried with ethyl acetate to provide a solid which is collected and washed. Th...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether.Ether.Ether
Ketone.Aromatic alcohol
C1COCO1
null
c1ccccc1.c1ccncc1.c1ccncc1
HO-
O
null
null
COCOc1cc(C2(C)OCCO2)ccc1C(=O)Nc1cccnc1C(=O)Nc1ccc(Cl)cn1>O>CC(=O)c1ccc(C(=O)Nc2cccnc2C(=O)Nc2ccc(Cl)cn2)c(O)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ca2ea7aa7d104799bcd14d3dc93f50d2
CC(=O)c1cccc(O)c1.COCCl>>COCOc1cccc(C(C)=O)c1
ClCOC.CC(=O)C=1C=CC=C(C1)O.C(C)(C)N(C(C)C)CC>>COCOC1=CC(=CC=C1)C(C)=O
[OH:4][c:5]1[cH:6][cH:7][cH:8][c:9]([C:10]([CH3:11])=[O:12])[cH:13]1.Cl[CH2:3][O:2][CH3:1]>>[CH3:1][O:2][CH2:3][O:4][c:5]1[cH:6][cH:7][cH:8][c:9]([C:10]([CH3:11])=[O:12])[cH:13]1
CC(=O)c1cccc(O)c1.COCCl
COCOc1cccc(C(C)=O)c1
null
null
C(Cl)Cl
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
6e90ffbf0683e1a3ee55c5e3ea453aefc5ddd369c0150ed0150f9546d7e47f4f
efd670663709b79afcad1306da9f69b33a0147cfa3639ca4c0b54b35ef4b1852
c1ccccc1
Cl-[CH2;D2;+0:1]-[#8:2]-[C;D1;H3:3].[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[C;D1;H3:3]-[#8:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]
64
[{"value": 64.0, "product": "COCOC1=CC(=CC=C1)C(C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 64.0, "product": "COCOC1=CC(=CC=C1)C(C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
30
MINUTE
To a stirred solution of 3-hydroxyacetophenone (20.40 g, 150 mmol) in CH2Cl2 (450 mL) at 0° C. under N2 was added N,N-diisopropylethylamine (52.25 mL, 300 mmol) followed by methyl chloromethyl ether (MOM chloride) (13.67 mL, 180 mmol) over a period of 30 min. The reaction was stirred at 0° C. for 30 min and then at roo...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ether.Aromatic alcohol
Ether.Ether
null
null
c1ccccc1
HCl
C(Cl)Cl
0
0.5
CC(=O)c1cccc(O)c1.COCCl>C(Cl)Cl>COCOc1cccc(C(C)=O)c1