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large_stringclasses
414 values
reaction_id
large_stringlengths
36
36
reaction_smiles
large_stringlengths
4
873
rxn_insight_reaction
large_stringlengths
19
1.07k
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large_stringlengths
14
3.37k
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large_stringlengths
1
581
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large_stringlengths
1
433
reagent_smiles
large_stringclasses
634 values
catalyst_smiles
large_stringlengths
1
683
solvent_smiles
large_stringlengths
1
245
rxn_insight_class
large_stringclasses
11 values
rxn_insight_name
large_stringclasses
346 values
rxn_insight_tag
large_stringlengths
64
64
rxn_insight_tag2
large_stringlengths
64
64
rxn_insight_scaffold
large_stringlengths
5
288
rxn_insight_template
large_stringlengths
24
2.64k
yield_percent
float64
-0.8
90,205,160,000B
yield_measurements
large_stringlengths
2
864
temperature_value
float64
-230
30.1k
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large_stringclasses
3 values
reaction_time_value
float64
0
4k
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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-c3a75813d0b24864aa4f7cd526efd6aa
ord-5147f22926644af284b6b32cf7616792
Clc1cccc(N2CCNCC2)c1Cl.O=C(CCCl)N1CCc2ccccc21>>O=C(CCN1CCN(c2cccc(Cl)c2Cl)CC1)N1CCc2ccccc21
Cl.ClC1=C(C=CC=C1Cl)N1CCNCC1.C([O-])([O-])=O.[K+].[K+].ClCCC(=O)N1CCC2=CC=CC=C12>>ClC1=C(C=CC=C1Cl)N1CCN(CC1)CCC(=O)N1CCC2=CC=CC=C12
[NH:5]1[CH2:6][CH2:7][N:8]([c:9]2[cH:10][cH:11][cH:12][c:13]([Cl:14])[c:15]2[Cl:16])[CH2:17][CH2:18]1.Cl[CH2:4][CH2:3][C:2](=[O:1])[N:19]1[CH2:20][CH2:21][c:22]2[cH:23][cH:24][cH:25][cH:26][c:27]21>>[O:1]=[C:2]([CH2:3][CH2:4][N:5]1[CH2:6][CH2:7][N:8]([c:9]2[cH:10][cH:11][cH:12][c:13]([Cl:14])[c:15]2[Cl:16])[CH2:17][CH2...
Clc1cccc(N2CCNCC2)c1Cl.O=C(CCCl)N1CCc2ccccc21
O=C(CCN1CCN(c2cccc(Cl)c2Cl)CC1)N1CCc2ccccc21
null
null
CC(CC)=O.CN(C=O)C
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
bad6b7d8e43c3debef0c262d60564e43415b41bcee72e526419c8c16be18fec1
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
O=C(CCN1CCN(c2ccccc2)CC1)N1CCc2ccccc21
Cl-[CH2;D2;+0:1]-[C:2]-[C:3](=[O;D1;H0:4])-[#7:5](-[C:6])-[c:7].[#7:8]1-[C:9]-[C:10]-[NH;D2;+0:11]-[C:12]-[C:13]-1>>[C:6]-[#7:5](-[C:3](=[O;D1;H0:4])-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:11]1-[C:10]-[C:9]-[#7:8]-[C:13]-[C:12]-1)-[c:7]
null
[]
50
CELSIUS
null
null
A mixture of 1-(2,3-dichlorophenyl)piperazine, hydrochloride (8.0 g) and potassium carbonate (15 g) in a mixture of butanone (50 mL) and dimethyl formamide (5 mL) was heated to 50° C. followed by the addition of 3-chloro-1-(2,3-dihydro-1H-indol-1-yl)propan-1-one (6.0 g). The resulting mixture was boiled under reflux fo...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1.c1ccccc1.c1ccc2c(c1)CC[NH]2
HCl
CC(CC)=O.CN(C=O)C
50
null
Clc1cccc(N2CCNCC2)c1Cl.O=C(CCCl)N1CCc2ccccc21>CC(CC)=O.CN(C=O)C>O=C(CCN1CCN(c2cccc(Cl)c2Cl)CC1)N1CCc2ccccc21
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-43478e91f8c64eae94c35aa44c372d3c
Clc1cccc(N2CCNCC2)c1Cl.O=C(CCCCBr)N1CCc2ccccc21>>O=C(CCCCN1CCN(c2cccc(Cl)c2Cl)CC1)N1CCc2ccccc21
Cl.ClC1=C(C=CC=C1Cl)N1CCNCC1.C(C)(C)N(CC)C(C)C.BrCCCCC(=O)N1CCC2=CC=CC=C12>>ClC1=C(C=CC=C1Cl)N1CCN(CC1)CCCCC(=O)N1CCC2=CC=CC=C12
[NH:7]1[CH2:8][CH2:9][N:10]([c:11]2[cH:12][cH:13][cH:14][c:15]([Cl:16])[c:17]2[Cl:18])[CH2:19][CH2:20]1.Br[CH2:6][CH2:5][CH2:4][CH2:3][C:2](=[O:1])[N:21]1[CH2:22][CH2:23][c:24]2[cH:25][cH:26][cH:27][cH:28][c:29]21>>[O:1]=[C:2]([CH2:3][CH2:4][CH2:5][CH2:6][N:7]1[CH2:8][CH2:9][N:10]([c:11]2[cH:12][cH:13][cH:14][c:15]([Cl...
Clc1cccc(N2CCNCC2)c1Cl.O=C(CCCCBr)N1CCc2ccccc21
O=C(CCCCN1CCN(c2cccc(Cl)c2Cl)CC1)N1CCc2ccccc21
null
null
CC(CC)=O
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
bad6b7d8e43c3debef0c262d60564e43415b41bcee72e526419c8c16be18fec1
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
O=C(CCCCN1CCN(c2ccccc2)CC1)N1CCc2ccccc21
Br-[CH2;D2;+0:1]-[C:2]-[C:3].[#7:4]1-[C:5]-[C:6]-[NH;D2;+0:7]-[C:8]-[C:9]-1>>[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:7]1-[C:6]-[C:5]-[#7:4]-[C:9]-[C:8]-1
null
[]
45
CELSIUS
null
null
A mixture of 1-(2,3-dichlorophenyl)piperazine hydrochloride (8.0 g) and diisopropylethylamine (15 mL) in butanone (50 mL) was heated to 45° C. followed by the addition of 5-bromo-1-(2,3-dihydro-1H-indol-1-yl)pentan-1-one (5.4 g). The resulting mixture was boiled under reflux for 40 h and filtered hot. The remaining org...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1.c1ccccc1.c1ccc2c(c1)CC[NH]2
HBr
CC(CC)=O
45
null
Clc1cccc(N2CCNCC2)c1Cl.O=C(CCCCBr)N1CCc2ccccc21>CC(CC)=O>O=C(CCCCN1CCN(c2cccc(Cl)c2Cl)CC1)N1CCc2ccccc21
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-0bb40dc82a3a4afea345f53344ad0ac4
Clc1ccccc1N1CCNCC1.O=C(CCCCl)N1CCc2ccccc21>>O=C(CCCN1CCN(c2ccccc2Cl)CC1)N1CCc2ccccc21
Cl.ClC1=C(C=CC=C1)N1CCNCC1.ClCCCC(=O)N1CCC2=CC=CC=C12>>ClC1=C(C=CC=C1)N1CCN(CC1)CCCC(=O)N1CCC2=CC=CC=C12
[NH:6]1[CH2:7][CH2:8][N:9]([c:10]2[cH:11][cH:12][cH:13][cH:14][c:15]2[Cl:16])[CH2:17][CH2:18]1.Cl[CH2:5][CH2:4][CH2:3][C:2](=[O:1])[N:19]1[CH2:20][CH2:21][c:22]2[cH:23][cH:24][cH:25][cH:26][c:27]21>>[O:1]=[C:2]([CH2:3][CH2:4][CH2:5][N:6]1[CH2:7][CH2:8][N:9]([c:10]2[cH:11][cH:12][cH:13][cH:14][c:15]2[Cl:16])[CH2:17][CH2...
Clc1ccccc1N1CCNCC1.O=C(CCCCl)N1CCc2ccccc21
O=C(CCCN1CCN(c2ccccc2Cl)CC1)N1CCc2ccccc21
null
null
null
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
bad6b7d8e43c3debef0c262d60564e43415b41bcee72e526419c8c16be18fec1
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
O=C(CCCN1CCN(c2ccccc2)CC1)N1CCc2ccccc21
Cl-[CH2;D2;+0:1]-[C:2]-[C:3]-[C:4](-[#7:5])=[O;D1;H0:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[#7:5]-[C:4](=[O;D1;H0:6])-[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[C:12]-[C:11]-1
null
[]
null
null
null
null
from 1-(2-chlorophenyl)piperazine, hydrochloride and 4-chloro-1-(2,3-dihydro-1H-indol-1-yl)butan-1-one. Mp 119–121° C. 1H NMR (DMSO-d6): 1.75–1.85 (m, 2H); 2.35–2.50 (m, 4H); 2.55 (s, 4H); 3.95 (s, 4H); 3.15 (t, 2H); 4.10 (t, 2H); 6.95 (t, 1H); 7.05 (t, 1H); 7.10 (d, 1H); 7.15 (t, 1H); 7.20 (d, 1H); 7.25 (t, 1H); 7.40 ...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1.c1ccccc1.c1ccc2c(c1)CC[NH]2
HCl
null
null
null
Clc1ccccc1N1CCNCC1.O=C(CCCCl)N1CCc2ccccc21>>O=C(CCCN1CCN(c2ccccc2Cl)CC1)N1CCc2ccccc21
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-22d2c8fcfcd84c428fb38bd7d6223c47
Clc1cccc(N2CCNCC2)c1.O=C(CCCCl)N1CCc2ccccc21>>O=C(CCCN1CCN(c2cccc(Cl)c2)CC1)N1CCc2ccccc21
Cl.Cl.ClC=1C=C(C=CC1)N1CCNCC1.ClCCCC(=O)N1CCC2=CC=CC=C12>>ClC=1C=C(C=CC1)N1CCN(CC1)CCCC(=O)N1CCC2=CC=CC=C12
[NH:6]1[CH2:7][CH2:8][N:9]([c:10]2[cH:11][cH:12][cH:13][c:14]([Cl:15])[cH:16]2)[CH2:17][CH2:18]1.Cl[CH2:5][CH2:4][CH2:3][C:2](=[O:1])[N:19]1[CH2:20][CH2:21][c:22]2[cH:23][cH:24][cH:25][cH:26][c:27]21>>[O:1]=[C:2]([CH2:3][CH2:4][CH2:5][N:6]1[CH2:7][CH2:8][N:9]([c:10]2[cH:11][cH:12][cH:13][c:14]([Cl:15])[cH:16]2)[CH2:17]...
Clc1cccc(N2CCNCC2)c1.O=C(CCCCl)N1CCc2ccccc21
O=C(CCCN1CCN(c2cccc(Cl)c2)CC1)N1CCc2ccccc21
null
null
null
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
bad6b7d8e43c3debef0c262d60564e43415b41bcee72e526419c8c16be18fec1
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
O=C(CCCN1CCN(c2ccccc2)CC1)N1CCc2ccccc21
Cl-[CH2;D2;+0:1]-[C:2]-[C:3]-[C:4](-[#7:5])=[O;D1;H0:6].[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1>>[#7:5]-[C:4](=[O;D1;H0:6])-[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:10]1-[C:9]-[C:8]-[#7:7]-[C:12]-[C:11]-1
null
[]
null
null
null
null
from 1-(3-chlorophenyl)piperazine, dihydrochloride and 4-chloro-1-(2,3-dihydro-1H-indol-1-yl)butan-1-one. Mp 102–107° C. 1H NMR (DMSO-d6): 1.75–1.85 (m, 2H); 2.35 (t, 2H); 2.45–2.55 (m, 6H); 3.10–3.20 (m, 6H); 4.10 (t, 2H); 6.75 (d, 1H); 6.85 (d, 1H); 6.90 (s, 1H); 6.95 (t, 1H); 7.10 (t, 1H); 7.15–7.25 (m, 2H); 8.10 (d...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CNCC[NH]1
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1.c1ccccc1.c1ccc2c(c1)CC[NH]2
HCl
null
null
null
Clc1cccc(N2CCNCC2)c1.O=C(CCCCl)N1CCc2ccccc21>>O=C(CCCN1CCN(c2cccc(Cl)c2)CC1)N1CCc2ccccc21
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d38d6c6f0c5a41f987fe4567dbc73965
O=C(CCN1CCN(c2cccc(Cl)c2Cl)CC1)N1CCc2ccccc21.O=C(CCN1CCN(c2cccc(Cl)c2Cl)CC1)N1CCc2ccccc21>>Cl.Clc1cccc(N2CCN(CCCN3CCc4ccccc43)CC2)c1Cl
ClC1=C(C=CC=C1Cl)N1CCN(CC1)CCC(=O)N1CCC2=CC=CC=C12.ClC1=C(C=CC=C1Cl)N1CCN(CC1)CCC(=O)N1CCC2=CC=CC=C12.[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl-].[Cl-].[Cl-].[Al+3]>>Cl.ClC1=C(C=CC=C1Cl)N1CCN(CC1)CCCN1CCC2=CC=CC=C12
O=C(CCN1CCN(c2cccc(Cl)c2[Cl:1])CC1)N1CCc2ccccc21.O=[C:14]([CH2:13][CH2:12][N:11]1[CH2:10][CH2:9][N:8]([c:7]2[cH:6][cH:5][cH:4][c:3]([Cl:2])[c:26]2[Cl:27])[CH2:25][CH2:24]1)[N:15]1[CH2:16][CH2:17][c:18]2[cH:19][cH:20][cH:21][cH:22][c:23]21>>[ClH:1].[Cl:2][c:3]1[cH:4][cH:5][cH:6][c:7]([N:8]2[CH2:9][CH2:10][N:11]([CH2:12]...
O=C(CCN1CCN(c2cccc(Cl)c2Cl)CC1)N1CCc2ccccc21.O=C(CCN1CCN(c2cccc(Cl)c2Cl)CC1)N1CCc2ccccc21
Cl.Clc1cccc(N2CCN(CCCN3CCc4ccccc43)CC2)c1Cl
null
null
O1CCCC1
Miscellaneous
OtherReaction
d26035f3bac55deefa8a21c9f376455003c56b07b74c94ffc8ec018719015d9a
52131a42c0c53e6809c722d2ccee9ef8cfbddf0557566469c2697d2902198f9c
c1ccc(N2CCN(CCCN3CCc4ccccc43)CC2)cc1
Cl-c1:c:c:c:c(-N2-C-C-N(-C-C-C(=O)-N3-C-C-c4:c:c:c:c:c:4-3)-C-C-2):c:1-[Cl;H0;D1;+0:1].O=[C;H0;D3;+0:2](-[C:3]-[C:4])-[#7:5](-[C:6])-[c:7]>>[C:4]-[C:3]-[CH2;D2;+0:2]-[#7:5](-[C:6])-[c:7].[ClH;D0;+0:1]
null
[]
5
CELSIUS
30
MINUTE
Lithium aluminium hydride (1.8 g) was suspended in tetrahydrofuran (30 mL) at 0° C., and the suspension was added a solution of aluminium trichloride (1.8 g) in tetrahydrofuran (30 mL) at 0–5° C. over 15 min. To this mixture, a solution of 1a, 3-[4-(2,3-dichlorophenyl)piperazin-1-yl]-1-(2,3-dihydro-1H-indol-1-yl)propan...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Tertiary amide.Tertiary amide.Tertiary amine.Tertiary amine
null
C1CNCCN1.c1ccccc1.c1ccc2c(c1)CCN2
null
c1ccccc1.C1C[NH]CC[NH]1.c1ccc2c(c1)CC[NH]2
HCl
O1CCCC1
5
0.5
O=C(CCN1CCN(c2cccc(Cl)c2Cl)CC1)N1CCc2ccccc21.O=C(CCN1CCN(c2cccc(Cl)c2Cl)CC1)N1CCc2ccccc21>O1CCCC1>Cl.Clc1cccc(N2CCN(CCCN3CCc4ccccc43)CC2)c1Cl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-5336bacc510e450986497bcfc85c5b3a
BrCCCc1c[nH]c2ccccc12.Clc1cccc(N2CCNCC2)c1Cl>>Cl.Clc1cccc(N2CCN(CCCc3c[nH]c4ccccc34)CC2)c1Cl
BrCCCC1=CNC2=CC=CC=C12.C([O-])([O-])=O.[K+].[K+].ClC1=C(C=CC=C1Cl)N1CCNCC1>>Cl.ClC1=C(C=CC=C1Cl)N1CCN(CC1)CCCC1=CNC2=CC=CC=C12
Br[CH2:12][CH2:13][CH2:14][c:15]1[cH:16][nH:17][c:18]2[cH:19][cH:20][cH:21][cH:22][c:23]12.[Cl:1][c:3]1[cH:4][cH:5][cH:6][c:7]([N:8]2[CH2:9][CH2:10][NH:11][CH2:24][CH2:25]2)[c:26]1[Cl:27]>>[ClH:1].[Cl:2][c:3]1[cH:4][cH:5][cH:6][c:7]([N:8]2[CH2:9][CH2:10][N:11]([CH2:12][CH2:13][CH2:14][c:15]3[cH:16][nH:17][c:18]4[cH:19]...
BrCCCc1c[nH]c2ccccc12.Clc1cccc(N2CCNCC2)c1Cl
Cl.Clc1cccc(N2CCN(CCCc3c[nH]c4ccccc34)CC2)c1Cl
null
null
C(C)#N
Functional Group Interconversion
N-alkylation of secondary amines with alkyl halides
34ecf698ba4c3d229136de4eafceea7425b5555faba807457b006ad2633abdb9
55cb0223d3535b9197d8f7ec112fe586b516e0475448133020904f1839920be7
c1ccc(N2CCN(CCCc3c[nH]c4ccccc34)CC2)cc1
Br-[CH2;D2;+0:1]-[C:2]-[C:3].[Cl;D1;H0:4]-[c:5](:[c:6]-[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1):[c;H0;D3;+0:13](-[Cl;H0;D1;+0:14]):[c:15]:[c:16]>>[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:10]1-[C:11]-[C:12]-[#7:7](-[c:6]:[c:5](-[Cl;D1;H0:4]):[c;H0;D3;+0:13](-[Cl;D1;H0:17]):[c:15]:[c:16])-[C:8]-[C:9]-1.[ClH;D0;+0:...
null
[]
null
null
null
null
A mixture of 3-(3-bromopropyl)-1H-indole (1.19 g), potassium carbonate (1.4 g) and 1-(2,3-dichlorophenyl)piperazine (1.27 g) in anhydrous acetonitrile (10 mL) was boiled under reflux for 5 h and cooled to room temperature. The mixture was added silicagel (7 g), and the solvent was evaporated in vacuo. The compound was ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary halide.Secondary amine
Aromatic halide.Tertiary amine
c1ccccc1.C1C[NH]CCN1
c1ccccc1.C1C[NH]CC[NH]1
c1ccccc1.C1C[NH]CC[NH]1.c1ccc2[nH]ccc2c1
null
C(C)#N
null
null
BrCCCc1c[nH]c2ccccc12.Clc1cccc(N2CCNCC2)c1Cl>C(C)#N>Cl.Clc1cccc(N2CCN(CCCc3c[nH]c4ccccc34)CC2)c1Cl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c9094f1f8b12457f9aa9cb2169657c75
BrCCCCc1c[nH]c2ccccc12.Clc1cccc(N2CCNCC2)c1Cl>>Cl.Clc1cccc(N2CCN(CCCCc3c[nH]c4ccccc34)CC2)c1Cl
ClC1=C(C=CC=C1Cl)N1CCNCC1.BrCCCCC1=CNC2=CC=CC=C12>>Cl.ClC1=C(C=CC=C1Cl)N1CCN(CC1)CCCCC1=CNC2=CC=CC=C12
Br[CH2:12][CH2:13][CH2:14][CH2:15][c:16]1[cH:17][nH:18][c:19]2[cH:20][cH:21][cH:22][cH:23][c:24]12.[Cl:1][c:3]1[cH:4][cH:5][cH:6][c:7]([N:8]2[CH2:9][CH2:10][NH:11][CH2:25][CH2:26]2)[c:27]1[Cl:28]>>[ClH:1].[Cl:2][c:3]1[cH:4][cH:5][cH:6][c:7]([N:8]2[CH2:9][CH2:10][N:11]([CH2:12][CH2:13][CH2:14][CH2:15][c:16]3[cH:17][nH:1...
BrCCCCc1c[nH]c2ccccc12.Clc1cccc(N2CCNCC2)c1Cl
Cl.Clc1cccc(N2CCN(CCCCc3c[nH]c4ccccc34)CC2)c1Cl
null
null
null
Functional Group Interconversion
N-alkylation of secondary amines with alkyl halides
34ecf698ba4c3d229136de4eafceea7425b5555faba807457b006ad2633abdb9
55cb0223d3535b9197d8f7ec112fe586b516e0475448133020904f1839920be7
c1ccc(N2CCN(CCCCc3c[nH]c4ccccc34)CC2)cc1
Br-[CH2;D2;+0:1]-[C:2]-[C:3].[Cl;D1;H0:4]-[c:5](:[c:6]-[#7:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-[C:12]-1):[c;H0;D3;+0:13](-[Cl;H0;D1;+0:14]):[c:15]:[c:16]>>[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:10]1-[C:11]-[C:12]-[#7:7](-[c:6]:[c:5](-[Cl;D1;H0:4]):[c;H0;D3;+0:13](-[Cl;D1;H0:17]):[c:15]:[c:16])-[C:8]-[C:9]-1.[ClH;D0;+0:...
null
[]
null
null
null
null
from 1-(2,3-dichlorophenyl)piperazine and 3-(4-bromobutyl)-1H-indole. Mp 121–122° C. 1H NMR (DMSO-d6): 1.45–1.55 (m, 2H); 1.65–1.75 (m, 2H); 2.35 (t, 2H); 2.50 (b s, 4H); 2.70 (t, 2H); 2.95 (b s, 4H); 6.95 (t, 1H); 7.05 (t, 1H); 7.10–7.15 (m, 2H); 7.25–7.30 (m, 2H); 7.35 (d, 1H); 7.50 (d, 1H); 10.75 (b s, 1H). Ms m/z: ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary halide.Secondary amine
Aromatic halide.Tertiary amine
c1ccccc1.C1C[NH]CCN1
c1ccccc1.C1C[NH]CC[NH]1
c1ccccc1.C1C[NH]CC[NH]1.c1ccc2[nH]ccc2c1
null
null
null
null
BrCCCCc1c[nH]c2ccccc12.Clc1cccc(N2CCNCC2)c1Cl>>Cl.Clc1cccc(N2CCN(CCCCc3c[nH]c4ccccc34)CC2)c1Cl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-399ea26007484f3396cee9cf2d6969d1
Clc1cccc(N2CCNCC2)c1Cl.Fc1ccc2[nH]cc(CCCCl)c2c1>>Fc1ccc2[nH]cc(CCCN3CCN(c4cccc(Cl)c4Cl)CC3)c2c1
ClC1=C(C=CC=C1Cl)N1CCNCC1.ClCCCC1=CNC2=CC=C(C=C12)F>>ClC1=C(C=CC=C1Cl)N1CCN(CC1)CCCC1=CNC2=CC=C(C=C12)F
[NH:12]1[CH2:13][CH2:14][N:15]([c:16]2[cH:17][cH:18][cH:19][c:20]([Cl:21])[c:22]2[Cl:23])[CH2:24][CH2:25]1.Cl[CH2:11][CH2:10][CH2:9][c:8]1[cH:7][nH:6][c:5]2[cH:4][cH:3][c:2]([F:1])[cH:27][c:26]21>>[F:1][c:2]1[cH:3][cH:4][c:5]2[nH:6][cH:7][c:8]([CH2:9][CH2:10][CH2:11][N:12]3[CH2:13][CH2:14][N:15]([c:16]4[cH:17][cH:18][c...
Clc1cccc(N2CCNCC2)c1Cl.Fc1ccc2[nH]cc(CCCCl)c2c1
Fc1ccc2[nH]cc(CCCN3CCN(c4cccc(Cl)c4Cl)CC3)c2c1
null
null
null
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
bad6b7d8e43c3debef0c262d60564e43415b41bcee72e526419c8c16be18fec1
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
c1ccc(N2CCN(CCCc3c[nH]c4ccccc34)CC2)cc1
Cl-[CH2;D2;+0:1]-[C:2]-[C:3].[#7:4]1-[C:5]-[C:6]-[NH;D2;+0:7]-[C:8]-[C:9]-1>>[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:7]1-[C:6]-[C:5]-[#7:4]-[C:9]-[C:8]-1
null
[]
null
null
null
null
from 1-(2,3-dichlorophenyl)piperazine and 3-(3-chloropropyl)-5-fluoro-1H-indole. Mp 147–148° C. 1H NMR (DMSO-d6): 1.75–1.85 (m, 2H); 2.30–2.45 (t, 2H); 2.45–2.60 (m, 2H); 2.70 (t, 2H); 3.00 (b s, 4H); 3.35 (b s, 2H); 6.85–6.95 (m, 1H); 7.05–7.15 (m, 1H); 7.20 (s, 1H); 7.20–7.35 (m, 4H); 10.85 (b s, 1H). Ms m/z: 406 (MH...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CNCC[NH]1
C1C[NH]CC[NH]1
c1ccc2[nH]ccc2c1.C1C[NH]CC[NH]1.c1ccccc1
HCl
null
null
null
Clc1cccc(N2CCNCC2)c1Cl.Fc1ccc2[nH]cc(CCCCl)c2c1>>Fc1ccc2[nH]cc(CCCN3CCN(c4cccc(Cl)c4Cl)CC3)c2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b5dd867193b449d4bcf48c923e1b0011
Clc1cccc(N2CCNCC2)c1Cl.O=C1CCc2ccccc2N1CCCCBr>>O=C1CCc2ccccc2N1CCCCN1CCN(c2cccc(Cl)c2Cl)CC1
Cl.ClC1=C(C=CC=C1Cl)N1CCNCC1.N.BrCCCCN1C(CCC2=CC=CC=C12)=O.C([O-])([O-])=O.[K+].[K+]>>ClC1=C(C=CC=C1Cl)N1CCN(CC1)CCCCN1C(CCC2=CC=CC=C12)=O
[NH:16]1[CH2:17][CH2:18][N:19]([c:20]2[cH:21][cH:22][cH:23][c:24]([Cl:25])[c:26]2[Cl:27])[CH2:28][CH2:29]1.Br[CH2:15][CH2:14][CH2:13][CH2:12][N:11]1[C:2](=[O:1])[CH2:3][CH2:4][c:5]2[cH:6][cH:7][cH:8][cH:9][c:10]21>>[O:1]=[C:2]1[CH2:3][CH2:4][c:5]2[cH:6][cH:7][cH:8][cH:9][c:10]2[N:11]1[CH2:12][CH2:13][CH2:14][CH2:15][N:...
Clc1cccc(N2CCNCC2)c1Cl.O=C1CCc2ccccc2N1CCCCBr
O=C1CCc2ccccc2N1CCCCN1CCN(c2cccc(Cl)c2Cl)CC1
null
null
CC(CC)=O.C(C)(=O)OCC
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
bad6b7d8e43c3debef0c262d60564e43415b41bcee72e526419c8c16be18fec1
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
O=C1CCc2ccccc2N1CCCCN1CCN(c2ccccc2)CC1
Br-[CH2;D2;+0:1]-[C:2]-[C:3].[#7:4]1-[C:5]-[C:6]-[NH;D2;+0:7]-[C:8]-[C:9]-1>>[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:7]1-[C:6]-[C:5]-[#7:4]-[C:9]-[C:8]-1
null
[]
null
null
null
null
The free base of 1-(2,3-dichlorophenyl)piperazine, hydrochloride (6.0 g) was liberated by the use ethyl acetate and aqueous ammonia. The remaining oil was dissolved in butanone (500 mL) followed by the addition of potassium carbonate (9.7 g), and the mixture was heated to reflux temperature. To this mixture was added a...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CNCC[NH]1
C1C[NH]CC[NH]1
c1ccc2c(c1)CCC[NH]2.C1C[NH]CC[NH]1.c1ccccc1
HBr
CC(CC)=O.C(C)(=O)OCC
null
null
Clc1cccc(N2CCNCC2)c1Cl.O=C1CCc2ccccc2N1CCCCBr>CC(CC)=O.C(C)(=O)OCC>O=C1CCc2ccccc2N1CCCCN1CCN(c2cccc(Cl)c2Cl)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-326998311bbe455d9881ea3eb9391ede
Clc1cccc(N2CCNCC2)c1Cl.Fc1ccc2c(c1)CCN2.O=C(Cl)CCBr>>O=C(CCN1CCN(c2cccc(Cl)c2Cl)CC1)N1CCc2cc(F)ccc21
ClC1=C(C=CC=C1Cl)N1CCNCC1.C(C)(C)N(CC)C(C)C.[Al+3].[Cl-].[Cl-].[Cl-].BrCCC(=O)Cl.ClCCl.C(C)(C)N(CC)C(C)C.FC=1C=C2CCNC2=CC1.[OH-].[Na+]>>ClC1=C(C=CC=C1Cl)N1CCN(CC1)CCC(=O)N1CCC2=CC(=CC=C12)F
[NH:5]1[CH2:6][CH2:7][N:8]([c:9]2[cH:10][cH:11][cH:12][c:13]([Cl:14])[c:15]2[Cl:16])[CH2:17][CH2:18]1.[NH:19]1[CH2:20][CH2:21][c:22]2[cH:23][c:24]([F:25])[cH:26][cH:27][c:28]21.Cl[C:2](=[O:1])[CH2:3][CH2:4]Br>>[O:1]=[C:2]([CH2:3][CH2:4][N:5]1[CH2:6][CH2:7][N:8]([c:9]2[cH:10][cH:11][cH:12][c:13]([Cl:14])[c:15]2[Cl:16])[...
Clc1cccc(N2CCNCC2)c1Cl.Fc1ccc2c(c1)CCN2.O=C(Cl)CCBr
O=C(CCN1CCN(c2cccc(Cl)c2Cl)CC1)N1CCc2cc(F)ccc21
null
null
C(C)#N
Acylation
OtherReaction
e6ee41d9f586f8b18421fe58ac66cc363ad58542c3491ff27206bb457448ba5a
ef8b84f1e1da90e48fb3c0bc44e43a80cb90e07afa1034aea7a1477489231c3f
O=C(CCN1CCN(c2ccccc2)CC1)N1CCc2ccccc21
Br-[CH2;D2;+0:1]-[C:2]-[C;H0;D3;+0:3](-Cl)=[O;D1;H0:4].[#7:5]1-[C:6]-[C:7]-[NH;D2;+0:8]-[C:9]-[C:10]-1.[c:11]:[c:12]1:[c:13]-[C:14]-[C:15]-[NH;D2;+0:16]-1>>[O;D1;H0:4]=[C;H0;D3;+0:3](-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:8]1-[C:7]-[C:6]-[#7:5]-[C:10]-[C:9]-1)-[N;H0;D3;+0:16]1-[C:15]-[C:14]-[c:13]:[c:12]-1:[c:11]
null
[]
null
null
8
HOUR
3-Bromopropanoyl chloride (1 g in 10 ml dry dichloromethane) was added with stirring at 0° C. to a suspension of 1 g Wang resin (Rapp polymere, loading 0.95 mmol/g) in 10 ml dry dichloromethane containing 5 equivalents of diisopropylethyl amine. The mixture was stirred overnight at room temperature, filtered and washed...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary halide.Secondary amine.Secondary amine
Tertiary amide.Tertiary amine
C1CNCC[NH]1.c1ccc2c(c1)CCN2
C1C[NH]CC[NH]1.c1ccc2c(c1)CC[NH]2
C1C[NH]CC[NH]1.c1ccccc1.c1ccc2c(c1)CC[NH]2
HCl.Br-
C(C)#N
null
8
Clc1cccc(N2CCNCC2)c1Cl.Fc1ccc2c(c1)CCN2.O=C(Cl)CCBr>C(C)#N>O=C(CCN1CCN(c2cccc(Cl)c2Cl)CC1)N1CCc2cc(F)ccc21
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-312d7d2a6a2543d7a04ff7f6190d2754
Clc1ncnc(Cl)n1.Nc1nc2ccccc2[nH]1>>Nc1nc2ccccc2n1-c1ncnc(Cl)n1
ClC1=NC=NC(=N1)Cl.CCN(C(C)C)C(C)C.O.O.NC=1NC2=C(N1)C=CC=C2>>ClC1=NC(=NC=N1)N1C(=NC2=C1C=CC=C2)N
Cl[c:11]1[n:12][cH:13][n:14][c:15]([Cl:16])[n:17]1.[NH2:1][c:2]1[n:3][c:4]2[cH:5][cH:6][cH:7][cH:8][c:9]2[nH:10]1>>[NH2:1][c:2]1[n:3][c:4]2[cH:5][cH:6][cH:7][cH:8][c:9]2[n:10]1-[c:11]1[n:12][cH:13][n:14][c:15]([Cl:16])[n:17]1
Clc1ncnc(Cl)n1.Nc1nc2ccccc2[nH]1
Nc1nc2ccccc2n1-c1ncnc(Cl)n1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
de8ca90b6a87d8cb2c34d2d3043201922cff5cf5653513773b5948279865a7ce
e3660767655c50df0f92afc78c794dd2af7cf646bf1430960eafd30c23bf3fa7
c1ccc2c(c1)ncn2-c1ncncn1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](-[Cl;D1;H0:6]):[#7;a:7]:1.[N;D1;H2:8]-[c:9]1:[#7;a:10]:[c:11](:[c:12]):[c:13](:[c:14]):[nH;D2;+0:15]:1>>[Cl;D1;H0:6]-[c:5]1:[#7;a:4]:[c:3]:[#7;a:2]:[c;H0;D3;+0:1](-[n;H0;D3;+0:15]2:[c:9](-[N;D1;H2:8]):[#7;a:10]:[c:11](:[c:12]):[c:13]:2:[c:14]):[#7;a:7]:1
83
[{"value": 83.0, "product": "ClC1=NC(=NC=N1)N1C(=NC2=C1C=CC=C2)N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 82.7, "product": "ClC1=NC(=NC=N1)N1C(=NC2=C1C=CC=C2)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
1.9
HOUR
To 1.0 g (6.67 mmol) of 2,4-dichloro-1,3,5-triazine in 3 mL of DMF at 0° C. is added 1.16 mL (6.67 mmol) of DIEA. The resulting yellow solution is stirred at 0° C. for 10 min when-888 mg (6.67 mmol) of 2-aminobenzimidazole is added portionwise over 5 min, followed by an additional 1 mL of DMF. The resulting mixture is ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
c1ncncn1.c1ccc2[nH]cnc2c1
c1nc2ccccc2[nH]1.c1ncncn1
c1nc2ccccc2[nH]1.c1ncncn1
HCl
CN(C)C=O
0
1.9
Clc1ncnc(Cl)n1.Nc1nc2ccccc2[nH]1>CN(C)C=O>Nc1nc2ccccc2n1-c1ncnc(Cl)n1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3775196ad1a841a887da7e8896b6bcf3
CC(=O)OC(C)=O.CCC(N)C(=O)O>>CCC(NC(C)=O)C(=O)O
NC(C(=O)O)CC.C(C)(=O)OC(C)=O>>C(C)(=O)NC(C(=O)O)CC
CC(=O)O[C:5]([CH3:6])=[O:7].[CH3:1][CH2:2][CH:3]([NH2:4])[C:8](=[O:9])[OH:10]>>[CH3:1][CH2:2][CH:3]([NH:4][C:5]([CH3:6])=[O:7])[C:8](=[O:9])[OH:10]
CC(=O)OC(C)=O.CCC(N)C(=O)O
CCC(NC(C)=O)C(=O)O
null
null
C(C)(=O)O
Acylation
Aminolysis of esters
87d35e51b477fc9a658a6f307eb56d84c8879182772c9dd3a42ec0d584fd2684
627cbc0550c9f51ad0105d9fcf46677e8c93bed87ee95bfe69292a82550c95b7
null
C-C(=O)-O-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[C:4]-[C:5](-[NH2;D1;+0:6])-[C:7](=[O;D1;H0:8])-[O;D1;H1:9]>>[C:4]-[C:5](-[NH;D2;+0:6]-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3])-[C:7](=[O;D1;H0:8])-[O;D1;H1:9]
null
[]
100
CELSIUS
2
HOUR
163 g (1.58 mol) 2-aminobutanoic acid are dissolved in acetic acid, and 242 g (2.37 mol) acetic anhydride are added dropwise. The mixture is stirred for 2 h at 100° C. until completion of reaction, then the solution is evaporated to dryness in vacuo. The solid residue is suspended in ethyl acetate, filtered and washed ...
10.6084/m9.figshare.5104873.v1
null
Anhydride.Primary amine
Secondary amide
null
null
null
HO-
C(C)(=O)O
100
2
CC(=O)OC(C)=O.CCC(N)C(=O)O>C(C)(=O)O>CCC(NC(C)=O)C(=O)O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-6e9da760204a424b95349e789bfbea5b
CCC(NC(C)=O)C(=O)O.CCOC(=O)C(=O)Cl>>CCOC(=O)C(=O)C(CC)NC(C)=O
ClC(C(=O)OCC)=O.C(C)(=O)NC(C(=O)O)CC.N1=CC=CC=C1>>C(C)(=O)NC(C(C(=O)OCC)=O)CC
O=C(O)[CH:8]([CH2:9][CH3:10])[NH:11][C:12]([CH3:13])=[O:14].Cl[C:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])=[O:7]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[C:6](=[O:7])[CH:8]([CH2:9][CH3:10])[NH:11][C:12]([CH3:13])=[O:14]
CCC(NC(C)=O)C(=O)O.CCOC(=O)C(=O)Cl
CCOC(=O)C(=O)C(CC)NC(C)=O
null
null
O1CCCC1
C-C Coupling
Ketonization by decarboxylation of acid halides
aaebaa0d813a71dc889ae147df75d12dcb32900152f1a5154d5b3ca46552ea1b
3f61ba26fe9791436c27b93d0c669474775a60e3446708a267a9de08824bde1e
null
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](=[O;D1;H0:4])-[#8:5]-[C:6].O-C(=O)-[CH;D3;+0:7](-[#7:8]-[C:9](-[C;D1;H3:10])=[O;D1;H0:11])-[C:12]-[C;D1;H3:13]>>[C:6]-[#8:5]-[C:3](=[O;D1;H0:4])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[CH;D3;+0:7](-[#7:8]-[C:9](-[C;D1;H3:10])=[O;D1;H0:11])-[C:12]-[C;D1;H3:13]
null
[]
null
null
null
null
9.2 g (63.4 mmol) 2-(acetylamino)butanoic acid are suspended in 120 ml tetrahydrofuran and heated to reflux together with 15.0 g (190 mmol) pyridine and a bit of N,N-dimethylaminopyridine. While heating at reflux, 17.3 g (127 mmol) ethyl chloro(oxo)acetate are added dropwise. The reaction mixture is heated at reflux un...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Carboxylic acid.Ester
Ketone
null
null
null
HCl
O1CCCC1
null
null
CCC(NC(C)=O)C(=O)O.CCOC(=O)C(=O)Cl>O1CCCC1>CCOC(=O)C(=O)C(CC)NC(C)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-923e5209c9ad44c6922b3b07fafeed4a
CCC(N)C(=O)O.O=C(Cl)C1CCCC1>>CCC(NC(=O)C1CCCC1)C(=O)O
NC(C(=O)O)CC.Cl[Si](C)(C)C.C1(CCCC1)C(=O)Cl.C(C)N(CC)CC>>C1(CCCC1)C(=O)NC(C(=O)O)CC
[CH3:1][CH2:2][CH:3]([NH2:4])[C:12](=[O:13])[OH:14].Cl[C:5](=[O:6])[CH:7]1[CH2:8][CH2:9][CH2:10][CH2:11]1>>[CH3:1][CH2:2][CH:3]([NH:4][C:5](=[O:6])[CH:7]1[CH2:8][CH2:9][CH2:10][CH2:11]1)[C:12](=[O:13])[OH:14]
CCC(N)C(=O)O.O=C(Cl)C1CCCC1
CCC(NC(=O)C1CCCC1)C(=O)O
null
null
ClCCl.O
Acylation
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
38143a4d536201990008fd6f2c68e6571a341d1c367481869fbbbe36cb038937
0e6ae078978e324f714e184b4f72826d4e3bf2d9ab22d6e9f73740af687be16f
C1CCCC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])-[C:5].[C:6]-[C:7](-[NH2;D1;+0:8])-[C:9](=[O;D1;H0:10])-[O;D1;H1:11]>>[C:4]-[C:3](-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:8]-[C:7](-[C:6])-[C:9](=[O;D1;H0:10])-[O;D1;H1:11])-[C:5]
null
[]
0
CELSIUS
1
HOUR
35 g (339 mmol) 2-aminobutanoic acid and 75.6 g (747 mmol) triethylamine are suspended in 300 ml of dichloromethane and stirred at 0° C. 81 g (747 mmol) chlorotrimethylsilane are added dropwise, then the mixture is stirred for 1 hour at room temperature and for 1 hour at 40° C. After cooling down to −10° C., 45 g (339 ...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amine
Secondary amide
null
null
C1CCCC1
HCl
ClCCl.O
0
1
CCC(N)C(=O)O.O=C(Cl)C1CCCC1>ClCCl.O>CCC(NC(=O)C1CCCC1)C(=O)O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2a59515024644f7f9268fc7d7abe72fa
CCC(NC(=O)C1CCCC1)C(=O)O.CCOC(=O)C(=O)Cl>>CCOC(=O)C(=O)C(CC)NC(=O)C1CCCC1
ClC(C(=O)OCC)=O.C1(CCCC1)C(=O)NC(C(=O)O)CC.N1=CC=CC=C1>>C1(CCCC1)C(=O)NC(C(C(=O)OCC)=O)CC
O[C:6](=[O:7])[CH:8]([CH2:9][CH3:10])[NH:11][C:12](=[O:13])[CH:14]1[CH2:15][CH2:16][CH2:17][CH2:18]1.O=C(Cl)[C:4]([O:3][CH2:2][CH3:1])=[O:5]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[C:6](=[O:7])[CH:8]([CH2:9][CH3:10])[NH:11][C:12](=[O:13])[CH:14]1[CH2:15][CH2:16][CH2:17][CH2:18]1
CCC(NC(=O)C1CCCC1)C(=O)O.CCOC(=O)C(=O)Cl
CCOC(=O)C(=O)C(CC)NC(=O)C1CCCC1
null
null
O1CCCC1
C-C Coupling
Ketonization by decarboxylation of acid halides
aaebaa0d813a71dc889ae147df75d12dcb32900152f1a5154d5b3ca46552ea1b
3f61ba26fe9791436c27b93d0c669474775a60e3446708a267a9de08824bde1e
C1CCCC1
Cl-C(=O)-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[C:4].O-[C;H0;D3;+0:5](=[O;D1;H0:6])-[C:7](-[C:8])-[#7:9]-[C:10]=[O;D1;H0:11]>>[C:4]-[#8:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C;H0;D3;+0:5](=[O;D1;H0:6])-[C:7](-[C:8])-[#7:9]-[C:10]=[O;D1;H0:11]
null
[]
null
null
null
null
1.6 g (8 mmol) 2-[(cyclopentylcarbonyl)amino]butanoic acid are suspended in 30 ml tetrahydrofuran and heated to reflux together with 1.91 g (24 mmol) pyridine and a bit of N,N-dimethylaminopyridine. While heating at reflux, 2.19 g (16 mmol) ethyl chloro(oxo)acetate are added dropwise. The reaction mixture is heated at ...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Carboxylic acid.Ester
Ketone
null
null
C1CCCC1
HCl
O1CCCC1
null
null
CCC(NC(=O)C1CCCC1)C(=O)O.CCOC(=O)C(=O)Cl>O1CCCC1>CCOC(=O)C(=O)C(CC)NC(=O)C1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-1e2a99234f7f4c078ff0b3dc5a472c6e
CCOC(=O)C(=O)C(CC)NC(C)=O.CCOC(=O)c1ccc(C(=N)N)cc1.NN>>CCOC(=O)c1ccc(-c2nnc(C(CC)NC(C)=O)c(=O)[nH]2)cc1
C(C)(=O)NC(C(C(=O)OCC)=O)CC.Cl.NC(C1=CC=C(C(=O)OCC)C=C1)=N.O.NN>>C(C)(=O)NC(CC)C=1C(NC(=NN1)C1=CC=C(C(=O)OCC)C=C1)=O
CCO[C:21]([C:13](=O)[CH:14]([CH2:15][CH3:16])[NH:17][C:18]([CH3:19])=[O:20])=[O:22].N[C:10]([c:9]1[cH:8][cH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[cH:25][cH:24]1)=[NH:23].[NH2:11][NH2:12]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][cH:8][c:9](-[c:10]2[n:11][n:12][c:13]([CH:14]([CH2:15][CH3:16])[NH:17][C:18]([CH3:1...
CCOC(=O)C(=O)C(CC)NC(C)=O.CCOC(=O)c1ccc(C(=N)N)cc1.NN
CCOC(=O)c1ccc(-c2nnc(C(CC)NC(C)=O)c(=O)[nH]2)cc1
null
null
C(C)O
Aromatic Heterocycle Formation
OtherReaction
e7bab37df0829099558b3ea1b1d6c14ca29d111a0fe7c4e70294ed15a1035365
b9a6c12d0e1239b0cb412542e52dae4bfecd4fc5a7cf6f6405348266ba7aff2e
O=c1cnnc(-c2ccccc2)[nH]1
C-C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C;H0;D3;+0:3](=O)-[C:4](-[C:5])-[#7:6]-[C:7](-[C;D1;H3:8])=[O;D1;H0:9].N-[C;H0;D3;+0:10](=[NH;D1;+0:11])-[c;H0;D3;+0:12](:[c:13]:[c:14]):[c:15]:[c:16].[NH2;D1;+0:17]-[NH2;D1;+0:18]>>[C:5]-[C:4](-[#7:6]-[C:7](-[C;D1;H3:8])=[O;D1;H0:9])-[c;H0;D3;+0:3]1:[n;H0;D2;+0:18]:[n;H0;D2;+0:17]:[...
null
[]
null
null
1
HOUR
1.98 g (8.66 mmol) ethyl 4-[amino(imino)methyl]benzoate hydrochloride are suspended in 50 ml of ethanol and 1.47 g (10.2 mmol, 1.2 equiv.) hydrazine hydrate are added. After stirring at room temperature for 1 hour, 2.59 g (13 mmol, 1.5 equiv.) of the compound of Example 2A, dissolved in 10 ml of ethanol, are added. The...
10.6084/m9.figshare.5104873.v1
null
Hydrazine.Ketone.Ester.Primary amine
null
null
c1cnncn1
c1ccccc1.c1cnncn1
HO-
C(C)O
null
1
CCOC(=O)C(=O)C(CC)NC(C)=O.CCOC(=O)c1ccc(C(=N)N)cc1.NN>C(C)O>CCOC(=O)c1ccc(-c2nnc(C(CC)NC(C)=O)c(=O)[nH]2)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d63c930ad8b54bf6bec77254a03a4189
CCOC(=O)C(=O)C(CC)NC(=O)C1CCCC1.N=C(N)c1ccc(C(N)=O)cc1.NN>>CCC(NC(=O)C1CCCC1)c1nnc(-c2ccc(C(N)=O)cc2)[nH]c1=O
C1(CCCC1)C(=O)NC(C(C(=O)OCC)=O)CC.Cl.NC(C1=CC=C(C(=O)N)C=C1)=N.O.NN>>C1(CCCC1)C(=O)NC(CC)C=1C(NC(=NN1)C1=CC=C(C(=O)N)C=C1)=O
CCO[C:26]([C:12](=O)[CH:3]([CH2:2][CH3:1])[NH:4][C:5](=[O:6])[CH:7]1[CH2:8][CH2:9][CH2:10][CH2:11]1)=[O:27].N=[C:15]([c:16]1[cH:17][cH:18][c:19]([C:20]([NH2:21])=[O:22])[cH:23][cH:24]1)[NH2:25].[NH2:13][NH2:14]>>[CH3:1][CH2:2][CH:3]([NH:4][C:5](=[O:6])[CH:7]1[CH2:8][CH2:9][CH2:10][CH2:11]1)[c:12]1[n:13][n:14][c:15](-[c...
CCOC(=O)C(=O)C(CC)NC(=O)C1CCCC1.N=C(N)c1ccc(C(N)=O)cc1.NN
CCC(NC(=O)C1CCCC1)c1nnc(-c2ccc(C(N)=O)cc2)[nH]c1=O
null
null
C(C)O
Aromatic Heterocycle Formation
OtherReaction
e7bab37df0829099558b3ea1b1d6c14ca29d111a0fe7c4e70294ed15a1035365
b9a6c12d0e1239b0cb412542e52dae4bfecd4fc5a7cf6f6405348266ba7aff2e
O=C(NCc1nnc(-c2ccccc2)[nH]c1=O)C1CCCC1
C-C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C;H0;D3;+0:3](=O)-[C:4](-[C:5])-[#7:6]-[C:7]=[O;D1;H0:8].N=[C;H0;D3;+0:9](-[NH2;D1;+0:10])-[c;H0;D3;+0:11](:[c:12]:[c:13]):[c:14]:[c:15].[NH2;D1;+0:16]-[NH2;D1;+0:17]>>[C:5]-[C:4](-[#7:6]-[C:7]=[O;D1;H0:8])-[c;H0;D3;+0:3]1:[n;H0;D2;+0:16]:[n;H0;D2;+0:17]:[c;H0;D3;+0:9](-[c;H0;D3;+0:1...
null
[]
60
CELSIUS
1
HOUR
2.84 g (14.2 mmol, 1 equiv.) 4-[amino(imino)methyl]benzamide hydrochloride are suspended in 10 ml of ethanol and 1.37 g (26.8 mmol, 1.2 equiv.) hydrazine hydrate are added. After stirring at 60° C. for 1 hour, 6.28 g (24.6 mmol, 1.1 equiv.) ethyl 3-[(cyclopentylcarbonyl)-amino]-2-oxopentanoate (Example 4A), dissolved i...
10.6084/m9.figshare.5104873.v1
null
Hydrazine.Ketone.Ester.Primary amine
null
null
c1cnncn1
C1CCCC1.c1cnncn1.c1ccccc1
HO-
C(C)O
60
1
CCOC(=O)C(=O)C(CC)NC(=O)C1CCCC1.N=C(N)c1ccc(C(N)=O)cc1.NN>C(C)O>CCC(NC(=O)C1CCCC1)c1nnc(-c2ccc(C(N)=O)cc2)[nH]c1=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c1660cc2acdb4b9a91f01468284b9579
CCC(N)c1nnc(-c2cccc([N+](=O)[O-])c2)[nH]c1=O.O=C(Cl)C1CCCC1>>CCC(NC(=O)C1CCCC1)c1nnc(-c2cccc([N+](=O)[O-])c2)[nH]c1=O
NC(CC)C=1C(NC(=NN1)C1=CC(=CC=C1)[N+](=O)[O-])=O.C1(CCCC1)C(=O)Cl>>[N+](=O)([O-])C=1C=C(C=CC1)C1=NN=C(C(N1)=O)C(CC)NC(=O)C1CCCC1
[CH3:1][CH2:2][CH:3]([NH2:4])[c:12]1[n:13][n:14][c:15](-[c:16]2[cH:17][cH:18][cH:19][c:20]([N+:21](=[O:22])[O-:23])[cH:24]2)[nH:25][c:26]1=[O:27].Cl[C:5](=[O:6])[CH:7]1[CH2:8][CH2:9][CH2:10][CH2:11]1>>[CH3:1][CH2:2][CH:3]([NH:4][C:5](=[O:6])[CH:7]1[CH2:8][CH2:9][CH2:10][CH2:11]1)[c:12]1[n:13][n:14][c:15](-[c:16]2[cH:17...
CCC(N)c1nnc(-c2cccc([N+](=O)[O-])c2)[nH]c1=O.O=C(Cl)C1CCCC1
CCC(NC(=O)C1CCCC1)c1nnc(-c2cccc([N+](=O)[O-])c2)[nH]c1=O
null
null
null
Acylation
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
38143a4d536201990008fd6f2c68e6571a341d1c367481869fbbbe36cb038937
0e6ae078978e324f714e184b4f72826d4e3bf2d9ab22d6e9f73740af687be16f
O=C(NCc1nnc(-c2ccccc2)[nH]c1=O)C1CCCC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])-[C:5].[#7;a:6]:[#7;a:7]:[c:8](-[C:9](-[C:10])-[NH2;D1;+0:11]):[c:12]:[#7;a:13]>>[#7;a:6]:[#7;a:7]:[c:8](-[C:9](-[C:10])-[NH;D2;+0:11]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])-[C:5]):[c:12]:[#7;a:13]
null
[]
null
null
null
null
In analogy to the procedure for Example 16A, 3.0 g (10.9 mmol) 6-(1-aminopropyl)-3-(3-nitrophenyl)-1,2,4-triazin-5(4H)-one (Example 15A), 2.2 g (16.3 mmol) cyclopentanecarbonyl chloride and proportionate amounts of the other reagents are used. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amine
Secondary amide
null
null
C1CCCC1.c1cnncn1.c1ccccc1
HCl
null
null
null
CCC(N)c1nnc(-c2cccc([N+](=O)[O-])c2)[nH]c1=O.O=C(Cl)C1CCCC1>>CCC(NC(=O)C1CCCC1)c1nnc(-c2cccc([N+](=O)[O-])c2)[nH]c1=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-cfcdddc5545c4ae5a70abee645f7a605
CC(C)(C)[C@@H]1CC[C@H](C(=O)Cl)CC1.CCC(N)c1nnc(-c2cccc([N+](=O)[O-])c2)[nH]c1=O>>CCC(NC(=O)[C@H]1CC[C@@H](C(C)(C)C)CC1)c1nnc(-c2cccc([N+](=O)[O-])c2)[nH]c1=O
NC(CC)C=1C(NC(=NN1)C1=CC(=CC=C1)[N+](=O)[O-])=O.C(C)(C)(C)[C@H]1CC[C@H](CC1)C(=O)Cl>>C(C)(C)(C)[C@H]1CC[C@H](CC1)C(=O)NC(CC)C=1C(NC(=NN1)C1=CC(=CC=C1)[N+](=O)[O-])=O
Cl[C:5](=[O:6])[C@@H:7]1[CH2:8][CH2:9][C@H:10]([C:11]([CH3:12])([CH3:13])[CH3:14])[CH2:15][CH2:16]1.[CH3:1][CH2:2][CH:3]([NH2:4])[c:17]1[n:18][n:19][c:20](-[c:21]2[cH:22][cH:23][cH:24][c:25]([N+:26](=[O:27])[O-:28])[cH:29]2)[nH:30][c:31]1=[O:32]>>[CH3:1][CH2:2][CH:3]([NH:4][C:5](=[O:6])[C@H:7]1[CH2:8][CH2:9][C@@H:10]([...
CC(C)(C)[C@@H]1CC[C@H](C(=O)Cl)CC1.CCC(N)c1nnc(-c2cccc([N+](=O)[O-])c2)[nH]c1=O
CCC(NC(=O)[C@H]1CC[C@@H](C(C)(C)C)CC1)c1nnc(-c2cccc([N+](=O)[O-])c2)[nH]c1=O
null
null
null
Acylation
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
38143a4d536201990008fd6f2c68e6571a341d1c367481869fbbbe36cb038937
0e6ae078978e324f714e184b4f72826d4e3bf2d9ab22d6e9f73740af687be16f
O=C(NCc1nnc(-c2ccccc2)[nH]c1=O)C1CCCCC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])-[C:5].[#7;a:6]:[#7;a:7]:[c:8](-[C:9](-[C:10])-[NH2;D1;+0:11]):[c:12]:[#7;a:13]>>[#7;a:6]:[#7;a:7]:[c:8](-[C:9](-[C:10])-[NH;D2;+0:11]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])-[C:5]):[c:12]:[#7;a:13]
null
[]
null
null
null
null
In analogy to the procedure for Example 16A, 3.2 g (11.6 mmol) 6-(1-aminopropyl)-3-(3-nitrophenyl)-1,2,4-triazin-5(4H)-one (Example 15A), 2.4 g (11.6 mmol) cis-4-tert.-butylcyclohexanecarbonyl chloride (Example 42A) and proportionate amounts of the other reagents are used. The crude product is used in the next step wit...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amine
Secondary amide
null
null
C1CCCCC1.c1cnncn1.c1ccccc1
HCl
null
null
null
CC(C)(C)[C@@H]1CC[C@H](C(=O)Cl)CC1.CCC(N)c1nnc(-c2cccc([N+](=O)[O-])c2)[nH]c1=O>>CCC(NC(=O)[C@H]1CC[C@@H](C(C)(C)C)CC1)c1nnc(-c2cccc([N+](=O)[O-])c2)[nH]c1=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-cb90fbfc22ad4b189a6629d9ec2fd186
CCC(NC(=O)C1CCCC1)c1nnc(-c2cccc([N+](=O)[O-])c2)[nH]c1=O>>CCc1nc(C2CCCC2)n2nc(-c3cccc([N+](=O)[O-])c3)[nH]c(=O)c12
[N+](=O)([O-])C=1C=C(C=CC1)C1=NN=C(C(N1)=O)C(CC)NC(=O)C1CCCC1.O=P(Cl)(Cl)Cl.C(=O)(O)[O-].[Na+]>>C1(CCCC1)C1=NC(=C2C(NC(=NN21)C2=CC(=CC=C2)[N+](=O)[O-])=O)CC
O=[C:5]([NH:4][CH:3]([CH2:2][CH3:1])[c:26]1[n:11][n:12][c:13](-[c:14]2[cH:15][cH:16][cH:17][c:18]([N+:19](=[O:20])[O-:21])[cH:22]2)[nH:23][c:24]1=[O:25])[CH:6]1[CH2:7][CH2:8][CH2:9][CH2:10]1>>[CH3:1][CH2:2][c:3]1[n:4][c:5]([CH:6]2[CH2:7][CH2:8][CH2:9][CH2:10]2)[n:11]2[n:12][c:13](-[c:14]3[cH:15][cH:16][cH:17][c:18]([N+...
CCC(NC(=O)C1CCCC1)c1nnc(-c2cccc([N+](=O)[O-])c2)[nH]c1=O
CCc1nc(C2CCCC2)n2nc(-c3cccc([N+](=O)[O-])c3)[nH]c(=O)c12
null
null
ClC(C)Cl
Aromatic Heterocycle Formation
OtherReaction
3c5d83dfcd7109f683218f4a2fbc6318a6967949b1a10b0e61cecdd6812a48d3
4c49decc0d3b49884847872e93a9c81862e00fd5fd04c96a796b9efc98b43f78
O=c1[nH]c(-c2ccccc2)nn2c(C3CCCC3)ncc12
O=[C;H0;D3;+0:1](-[NH;D2;+0:2]-[CH;D3;+0:3](-[C:4]-[C;D1;H3:5])-[c:6]1:[n;H0;D2;+0:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:1=[O;D1;H0:12])-[C:13](-[C:14])-[C:15]>>[C:14]-[C:13](-[c;H0;D3;+0:1]1:[n;H0;D2;+0:2]:[c;H0;D3;+0:3](-[C:4]-[C;D1;H3:5]):[c:6]2:[c:11](=[O;D1;H0:12]):[#7;a:10]:[c:9]:[#7;a:8]:[n;H0;D3;+0:7]:2:1)-[C:15]
null
[]
0
CELSIUS
null
null
3.5 g (9.4 mmol) N-{1-[3-(3-nitrophenyl)-5-oxo-4,5-dihydro-1,2,4-triazin-6-yl]propyl}-cyclopentanecarboxamide (Example 19A) are suspended in 60 ml dichloroethane, and 1.45 g (9.4 mmol) phosphoroxychloride are added. The mixture is stirred at reflux for 3 hour. After cooling down to 0° C., 10 ml saturated NaHCO3 (aq) is...
10.6084/m9.figshare.5104873.v1
null
Secondary amide
null
c1cnncn1
c1ncc2cncn2n1
C1CCCC1.c1ncc2cncn2n1.c1ccccc1
HO-
ClC(C)Cl
0
null
CCC(NC(=O)C1CCCC1)c1nnc(-c2cccc([N+](=O)[O-])c2)[nH]c1=O>ClC(C)Cl>CCc1nc(C2CCCC2)n2nc(-c3cccc([N+](=O)[O-])c3)[nH]c(=O)c12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-dc632e6c43e7444987fca0e1a90e6503
CCC(NC(=O)[C@H]1CC[C@@H](C(C)(C)C)CC1)c1nnc(-c2cccc([N+](=O)[O-])c2)[nH]c1=O>>CCc1nc(C2CCC(C(C)(C)C)CC2)n2nc(-c3cccc([N+](=O)[O-])c3)[nH]c(=O)c12
C(C)(C)(C)[C@H]1CC[C@H](CC1)C(=O)NC(CC)C=1C(NC(=NN1)C1=CC(=CC=C1)[N+](=O)[O-])=O.P(=O)(Cl)(Cl)Cl>>C(C)(C)(C)C1CCC(CC1)C1=NC(=C2C(NC(=NN21)C2=CC(=CC=C2)[N+](=O)[O-])=O)CC
O=[C:5]([NH:4][CH:3]([CH2:2][CH3:1])[c:31]1[n:16][n:17][c:18](-[c:19]2[cH:20][cH:21][cH:22][c:23]([N+:24](=[O:25])[O-:26])[cH:27]2)[nH:28][c:29]1=[O:30])[C@H:6]1[CH2:7][CH2:8][C@@H:9]([C:10]([CH3:11])([CH3:12])[CH3:13])[CH2:14][CH2:15]1>>[CH3:1][CH2:2][c:3]1[n:4][c:5]([CH:6]2[CH2:7][CH2:8][CH:9]([C:10]([CH3:11])([CH3:1...
CCC(NC(=O)[C@H]1CC[C@@H](C(C)(C)C)CC1)c1nnc(-c2cccc([N+](=O)[O-])c2)[nH]c1=O
CCc1nc(C2CCC(C(C)(C)C)CC2)n2nc(-c3cccc([N+](=O)[O-])c3)[nH]c(=O)c12
null
null
null
Aromatic Heterocycle Formation
OtherReaction
3c5d83dfcd7109f683218f4a2fbc6318a6967949b1a10b0e61cecdd6812a48d3
4c49decc0d3b49884847872e93a9c81862e00fd5fd04c96a796b9efc98b43f78
O=c1[nH]c(-c2ccccc2)nn2c(C3CCCCC3)ncc12
O=[C;H0;D3;+0:1](-[NH;D2;+0:2]-[CH;D3;+0:3](-[C:4]-[C;D1;H3:5])-[c:6]1:[n;H0;D2;+0:7]:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:1=[O;D1;H0:12])-[C@@H;D3;+0:13](-[C:14]-[C:15])-[C:16]-[C:17]>>[C:15]-[C:14]-[CH;D3;+0:13](-[c;H0;D3;+0:1]1:[n;H0;D2;+0:2]:[c;H0;D3;+0:3](-[C:4]-[C;D1;H3:5]):[c:6]2:[c:11](=[O;D1;H0:12]):[#7;a:10]:[c:9]...
null
[]
null
null
null
null
In analogy to the procedure for Example 21A, 5.1 g (11.6 mmol) crude cis-4-tert-butyl-N-{1-[3-(3-nitrophenyl)-5-oxo-4,5-dihydro-1,2,4-triazin-6-yl]propyl}cyclo-hexanecarboxamide (Example 20A), 2.7 g (17.4 mmol) phosphoric trichloride are stirred at reflux for 3 hours and proportionate amounts of the solvents are used. ...
10.6084/m9.figshare.5104873.v1
null
Secondary amide
null
c1cnncn1
c1ncc2cncn2n1
C1CCCCC1.c1ncc2cncn2n1.c1ccccc1
HO-
null
null
null
CCC(NC(=O)[C@H]1CC[C@@H](C(C)(C)C)CC1)c1nnc(-c2cccc([N+](=O)[O-])c2)[nH]c1=O>>CCc1nc(C2CCC(C(C)(C)C)CC2)n2nc(-c3cccc([N+](=O)[O-])c3)[nH]c(=O)c12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-22e1a08ab57f4e1e9d83778a11c66ea6
CCOC(=O)C(=O)C(CC)NC(C)=O.N=C(N)c1cccc(Br)c1.NN>>CCC(NC(C)=O)c1nnc(-c2cccc(Br)c2)[nH]c1=O
C(C)(=O)NC(C(C(=O)OCC)=O)CC.Cl.BrC=1C=C(C=CC1)C(N)=N.O.NN>>BrC=1C=C(C=CC1)C1=NN=C(C(N1)=O)C(CC)NC(C)=O
CCO[C:20]([C:8](=O)[CH:3]([CH2:2][CH3:1])[NH:4][C:5]([CH3:6])=[O:7])=[O:21].N=[C:11]([c:12]1[cH:13][cH:14][cH:15][c:16]([Br:17])[cH:18]1)[NH2:19].[NH2:9][NH2:10]>>[CH3:1][CH2:2][CH:3]([NH:4][C:5]([CH3:6])=[O:7])[c:8]1[n:9][n:10][c:11](-[c:12]2[cH:13][cH:14][cH:15][c:16]([Br:17])[cH:18]2)[nH:19][c:20]1=[O:21]
CCOC(=O)C(=O)C(CC)NC(C)=O.N=C(N)c1cccc(Br)c1.NN
CCC(NC(C)=O)c1nnc(-c2cccc(Br)c2)[nH]c1=O
null
null
C(C)O
Aromatic Heterocycle Formation
OtherReaction
e7bab37df0829099558b3ea1b1d6c14ca29d111a0fe7c4e70294ed15a1035365
b9a6c12d0e1239b0cb412542e52dae4bfecd4fc5a7cf6f6405348266ba7aff2e
O=c1cnnc(-c2ccccc2)[nH]1
C-C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C;H0;D3;+0:3](=O)-[C:4](-[C:5])-[#7:6]-[C:7](-[C;D1;H3:8])=[O;D1;H0:9].N=[C;H0;D3;+0:10](-[NH2;D1;+0:11])-[c;H0;D3;+0:12](:[c:13]:[c:14]):[c:15]:[c:16].[NH2;D1;+0:17]-[NH2;D1;+0:18]>>[C:5]-[C:4](-[#7:6]-[C:7](-[C;D1;H3:8])=[O;D1;H0:9])-[c;H0;D3;+0:3]1:[n;H0;D2;+0:18]:[n;H0;D2;+0:17]:...
null
[]
null
null
1
HOUR
2.02 g (8.6 mmol, 1 equiv.) 3-bromobenzenecarboximidamide hydrochloride (Example 31A) are suspended in 50 ml of ethanol, and 1.47 g (10.2 mmol, 1.2 equiv.) hydrazine hydrate are added. After stirring at room temperature for 1 hour, 2.59 g (13 mmol, 1.5 equiv.) of the compound of Example 2A, dissolved in 10 l of ethanol...
10.6084/m9.figshare.5104873.v1
null
Hydrazine.Ketone.Ester.Primary amine
null
null
c1cnncn1
c1cnncn1.c1ccccc1
HO-
C(C)O
null
1
CCOC(=O)C(=O)C(CC)NC(C)=O.N=C(N)c1cccc(Br)c1.NN>C(C)O>CCC(NC(C)=O)c1nnc(-c2cccc(Br)c2)[nH]c1=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-93fdfe881a7d4298bc877d00cd996986
CC(C)(C)[C@@H]1CC[C@H](C(=O)Cl)CC1.CCC(N)c1nnc(-c2ccc(Br)cc2)[nH]c1=O>>CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3ccc(Br)cc3)[nH]c(=O)c12
NC(CC)C=1C(NC(=NN1)C1=CC=C(C=C1)Br)=O.C(C)(C)(C)[C@H]1CC[C@H](CC1)C(=O)Cl>>BrC1=CC=C(C=C1)C1=NN2C(C(N1)=O)=C(N=C2[C@@H]2CC[C@@H](CC2)C(C)(C)C)CC
O=[C:5](Cl)[C@@H:6]1[CH2:7][CH2:8][C@H:9]([C:10]([CH3:11])([CH3:12])[CH3:13])[CH2:14][CH2:15]1.[CH3:1][CH2:2][CH:3]([NH2:4])[c:29]1[n:16][n:17][c:18](-[c:19]2[cH:20][cH:21][c:22]([Br:23])[cH:24][cH:25]2)[nH:26][c:27]1=[O:28]>>[CH3:1][CH2:2][c:3]1[n:4][c:5]([C@H:6]2[CH2:7][CH2:8][C@@H:9]([C:10]([CH3:11])([CH3:12])[CH3:1...
CC(C)(C)[C@@H]1CC[C@H](C(=O)Cl)CC1.CCC(N)c1nnc(-c2ccc(Br)cc2)[nH]c1=O
CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3ccc(Br)cc3)[nH]c(=O)c12
null
null
null
Aromatic Heterocycle Formation
OtherReaction
d528f61cb17ffa5934389707620e92dc49083bef6ae6ec9976a5efa729d467e2
f4550a08821e4f2624eeee345c16eafd026df7c9988e01c5dbe20cc7df2780e1
O=c1[nH]c(-c2ccccc2)nn2c(C3CCCCC3)ncc12
Cl-[C;H0;D3;+0:1](=O)-[C:2](-[C:3])-[C:4].[C;D1;H3:5]-[C:6]-[CH;D3;+0:7](-[NH2;D1;+0:8])-[c:9]1:[n;H0;D2;+0:10]:[#7;a:11]:[c:12]:[#7;a:13]:[c:14]:1=[O;D1;H0:15]>>[C:3]-[C:2](-[c;H0;D3;+0:1]1:[n;H0;D2;+0:8]:[c;H0;D3;+0:7](-[C:6]-[C;D1;H3:5]):[c:9]2:[c:14](=[O;D1;H0:15]):[#7;a:13]:[c:12]:[#7;a:11]:[n;H0;D3;+0:10]:2:1)-[C...
null
[]
null
null
null
null
In analogy to the procedure for Example 23A, 7.6 g (24.6 mmol) 6-(1-aminopropyl)-3-(4-bromophenyl)-1,2,4-triazin-5(4H)-one (Example 29A), 4.98 g (24.55 mmol) cis-4-tert-butylcyclohexylcarbonyl chloride (Example 42A) and proportionate amounts of the other reagents are used. Conditions: See reaction.notes.procedure_detai...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amine
null
c1cnncn1
c1ncc2cncn2n1
C1CCCCC1.c1ncc2cncn2n1.c1ccccc1
HCl
null
null
null
CC(C)(C)[C@@H]1CC[C@H](C(=O)Cl)CC1.CCC(N)c1nnc(-c2ccc(Br)cc2)[nH]c1=O>>CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3ccc(Br)cc3)[nH]c(=O)c12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c56de4fcd326441085356916ca06878c
N#Cc1cccc(Br)c1.[Cl-].[NH4+]>>Cl.N=C(N)c1cccc(Br)c1
BrC=1C=C(C#N)C=CC1.[Cl-].[NH4+].C[Al](C)C.CO>>Cl.BrC=1C=C(C=CC1)C(N)=N
[N:2]#[C:3][c:5]1[cH:6][cH:7][cH:8][c:9]([Br:10])[cH:11]1.[Cl-:1].[NH4+:4]>>[ClH:1].[NH:2]=[C:3]([NH2:4])[c:5]1[cH:6][cH:7][cH:8][c:9]([Br:10])[cH:11]1
N#Cc1cccc(Br)c1.[Cl-].[NH4+]
Cl.N=C(N)c1cccc(Br)c1
null
null
CCCCCC.C1(=CC=CC=C1)C
Functional Group Interconversion
OtherReaction
3b047a13c16a607c445b1c419e256808e8c9a0097d8fb9efd4e7970deb782b70
2882e57127fc469aa16ca9a2fd53388b6d97c74c76c010e6eb01be5726f46aa5
c1ccccc1
[Cl-;H0;D0:1].[N;H0;D1;+0:2]#[C;H0;D2;+0:3]-[c:4](:[c:5]):[c:6].[NH4+;D0:7]>>[ClH;D0;+0:1].[NH2;D1;+0:7]-[C;H0;D3;+0:3](=[NH;D1;+0:2])-[c:4](:[c:5]):[c:6]
null
[]
0
CELSIUS
null
null
1.18 g (22 mmol, 2 equiv.) ammonium chloride are suspended in 40 ml of dry toluene under an argon atmosphere, and the mixture is cooled to 0° C. 11 ml (22 mmol, 2 equiv.) of a 2M solution of trimethylaluminium in hexane are added dropwise, and the reaction mixture is stirred at room temperature until no more evolution ...
10.6084/m9.figshare.5104873.v1
null
Nitrile
Primary amine
null
null
c1ccccc1
null
CCCCCC.C1(=CC=CC=C1)C
0
null
N#Cc1cccc(Br)c1.[Cl-].[NH4+]>CCCCCC.C1(=CC=CC=C1)C>Cl.N=C(N)c1cccc(Br)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-da9f0d343f6d4457a3b2671de9eb68a5
CC(C)(C)[C@@H]1CC[C@H](C(=O)O)CC1.O=C(Cl)C(=O)Cl>>CC(C)(C)[C@@H]1CC[C@H](C(=O)Cl)CC1
C(C)(C)(C)[C@H]1CC[C@H](CC1)C(=O)O.C(C(=O)Cl)(=O)Cl>>C(C)(C)(C)[C@H]1CC[C@H](CC1)C(=O)Cl
O[C:9]([C@@H:8]1[CH2:7][CH2:6][C@H:5]([C:2]([CH3:1])([CH3:3])[CH3:4])[CH2:13][CH2:12]1)=[O:10].O=C(Cl)C(=O)[Cl:11]>>[CH3:1][C:2]([CH3:3])([CH3:4])[C@H:5]1[CH2:6][CH2:7][C@@H:8]([C:9](=[O:10])[Cl:11])[CH2:12][CH2:13]1
CC(C)(C)[C@@H]1CC[C@H](C(=O)O)CC1.O=C(Cl)C(=O)Cl
CC(C)(C)[C@@H]1CC[C@H](C(=O)Cl)CC1
null
null
ClCCl
Functional Group Interconversion
Alcohol to chloride_Other
013cec2edeb273a7a148f349d36a52d99ff4e7bcf8eed78085df830088e387ac
aedb1f68dc5b7eb0583043e1125b741382b17974140a2f46554f0110e2ddc884
C1CCCCC1
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]>>[C:5]-[C:4](-[C;H0;D3;+0:2](-[Cl;H0;D1;+0:1])=[O;D1;H0:3])-[C:6]
null
[]
null
null
1
HOUR
2.0 g (10.85 mmol) cis-4-tert-Butylcyclohexanecarboxylic acid are dissolved in 50 ml dichloromethane, 1.65 g (13.02 mmol) ethanedioyl dichloride are added and the solution is stirred at room temperature for one hour. The mixture is then stirred at reflux for two hours and, after cooling down to room temperature, evapor...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Acyl halide.Carboxylic acid
Acyl halide
null
null
C1CCCCC1
HCl
ClCCl
null
1
CC(C)(C)[C@@H]1CC[C@H](C(=O)O)CC1.O=C(Cl)C(=O)Cl>ClCCl>CC(C)(C)[C@@H]1CC[C@H](C(=O)Cl)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-57330aed75694e0fb1c2e0f3489fd77b
CC(C)(C)[C@@H]1CC[C@@H](C(=O)O)CC1.O=C(Cl)C(=O)Cl>>CC(C)(C)[C@@H]1CC[C@@H](C(=O)Cl)CC1
C(C(=O)Cl)(=O)Cl.C(C)(C)(C)[C@@H]1CC[C@H](CC1)C(=O)O>>C(C)(C)(C)[C@@H]1CC[C@H](CC1)C(=O)Cl
O[C:9]([C@H:8]1[CH2:7][CH2:6][C@H:5]([C:2]([CH3:1])([CH3:3])[CH3:4])[CH2:13][CH2:12]1)=[O:10].O=C(Cl)C(=O)[Cl:11]>>[CH3:1][C:2]([CH3:3])([CH3:4])[C@H:5]1[CH2:6][CH2:7][C@H:8]([C:9](=[O:10])[Cl:11])[CH2:12][CH2:13]1
CC(C)(C)[C@@H]1CC[C@@H](C(=O)O)CC1.O=C(Cl)C(=O)Cl
CC(C)(C)[C@@H]1CC[C@@H](C(=O)Cl)CC1
null
CN(C)C=O
ClCCl
Functional Group Interconversion
Alcohol to chloride_Other
013cec2edeb273a7a148f349d36a52d99ff4e7bcf8eed78085df830088e387ac
aedb1f68dc5b7eb0583043e1125b741382b17974140a2f46554f0110e2ddc884
C1CCCCC1
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]>>[C:5]-[C:4](-[C;H0;D3;+0:2](-[Cl;H0;D1;+0:1])=[O;D1;H0:3])-[C:6]
null
[]
null
null
1
HOUR
11.0 g (59.7 mmol) trans-4-tert-Butylcyclohexanecarboxylic acid are dissolved in 400 ml dichloromethane plus a few drops of DMF, 9.09 g (71.6 mmol) ethanedioyl dichloride are added and the solution is stirred at room temperature for one hour. The mixture is then stirred at reflux for two hours and, after cooling down t...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Acyl halide.Carboxylic acid
Acyl halide
null
null
C1CCCCC1
HCl
CN(C)C=O.ClCCl
null
1
CC(C)(C)[C@@H]1CC[C@@H](C(=O)O)CC1.O=C(Cl)C(=O)Cl>CN(C)C=O.ClCCl>CC(C)(C)[C@@H]1CC[C@@H](C(=O)Cl)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-ca737ecba18b4b259414def625785f5c
CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3ccc([N+](=O)[O-])cc3)[nH]c(=O)c12>>CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3ccc(N)cc3)[nH]c(=O)c12
C(C)(C)(C)[C@H]1CC[C@H](CC1)C1=NC(=C2C(NC(=NN21)C2=CC=C(C=C2)[N+](=O)[O-])=O)CC.[H][H]>>NC1=CC=C(C=C1)C1=NN2C(C(N1)=O)=C(N=C2[C@@H]2CC[C@@H](CC2)C(C)(C)C)CC
O=[N+:23]([O-])[c:22]1[cH:21][cH:20][c:19](-[c:18]2[n:17][n:16]3[c:5]([C@H:6]4[CH2:7][CH2:8][C@@H:9]([C:10]([CH3:11])([CH3:12])[CH3:13])[CH2:14][CH2:15]4)[n:4][c:3]([CH2:2][CH3:1])[c:29]3[c:27](=[O:28])[nH:26]2)[cH:25][cH:24]1>>[CH3:1][CH2:2][c:3]1[n:4][c:5]([C@H:6]2[CH2:7][CH2:8][C@@H:9]([C:10]([CH3:11])([CH3:12])[CH3...
CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3ccc([N+](=O)[O-])cc3)[nH]c(=O)c12
CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3ccc(N)cc3)[nH]c(=O)c12
null
[Pd]
O1CCCC1
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
O=c1[nH]c(-c2ccccc2)nn2c(C3CCCCC3)ncc12
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
null
null
null
null
580 mg (1.37 mmol) cis-7-(4-tert-butylcyclohexyl)-5-ethyl-2-(4-nitrophenyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one (Example 36A) are dissolved in 50 ml tetrahydrofuran and catalytic amounts of palladium (10% on charcoal) are added. The mixture is stirred for 18 hour at room temperature in a 3 bar hydrogen atmosphere. Th...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
C1CCCCC1.c1ncc2cncn2n1.c1ccccc1
Other
[Pd].O1CCCC1
null
null
CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3ccc([N+](=O)[O-])cc3)[nH]c(=O)c12>[Pd].O1CCCC1>CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3ccc(N)cc3)[nH]c(=O)c12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-706b6d16575d4ae18beff0d43bed92fb
C=CC(=O)OCC.CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3cccc(Br)c3)[nH]c(=O)c12>>CCOC(=O)/C=C/c1cccc(-c2nn3c([C@H]4CC[C@@H](C(C)(C)C)CC4)nc(CC)c3c(=O)[nH]2)c1
BrC=1C=C(C=CC1)C1=NN2C(C(N1)=O)=C(N=C2[C@@H]2CC[C@@H](CC2)C(C)(C)C)CC.C(C=C)(=O)OCC.C(C)N(CC)CC>>C(C)(C)(C)[C@H]1CC[C@H](CC1)C1=NC(=C2C(NC(=NN21)C=2C=C(C=CC2)/C=C/C(=O)OCC)=O)CC
[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]=[CH2:7].Br[c:8]1[cH:9][cH:10][cH:11][c:12](-[c:13]2[n:14][n:15]3[c:16]([c:17]([CH2:18][CH3:19])[n:20][c:21]3[C@H:22]3[CH2:23][CH2:24][C@@H:25]([C:26]([CH3:27])([CH3:28])[CH3:29])[CH2:30][CH2:31]3)[c:32](=[O:33])[nH:34]2)[cH:35]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])/[CH:6]=[CH:7]/[c:8...
C=CC(=O)OCC.CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3cccc(Br)c3)[nH]c(=O)c12
CCOC(=O)/C=C/c1cccc(-c2nn3c([C@H]4CC[C@@H](C(C)(C)C)CC4)nc(CC)c3c(=O)[nH]2)c1
null
Cl[Pd]([P](C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3)([P](C4=CC=CC=C4)(C5=CC=CC=C5)C6=CC=CC=C6)Cl
CN(C)C=O
C-C Coupling
Heck terminal vinyl
55becfded1a3842d5a03bbf3e1610411c659aff0806930400c4db2ef61f9c87f
4b186811a4930853b446d93d9faa39b267bddb9ce0b8021bda5c5a3b2bc69f0b
O=c1[nH]c(-c2ccccc2)nn2c(C3CCCCC3)ncc12
Br-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C:6]-[#8:7]-[C:8](=[O;D1;H0:9])-[C:10]=[CH2;D1;+0:11]>>[C:6]-[#8:7]-[C:8](=[O;D1;H0:9])/[C:10]=[CH;D2;+0:11]/[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]
null
[]
null
null
null
null
740 mg (1.62 mmol) cis-2-(3-bromophenyl)-7-(4-tert-butylcyclohexyl)-5-ethylimidazo[5,1-f][1,2,4]triazin-4(3H)-one (Example 27A), 1.6 g (16.2 mmol) ethyl acrylate, 327 mg (3.24 mmol) triethylamine and 227 mg (0.32 mmol) dichlorobis(triphenylphosphine)palladium(II) are stirred at 120° C. in 20 ml DMF in an argon atmosphe...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Vinyl
null
c1ccccc1
c1ccccc1
c1ccccc1.c1ncc2cncn2n1.C1CCCCC1
HBr
Cl[Pd]([P](C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3)([P](C4=CC=CC=C4)(C5=CC=CC=C5)C6=CC=CC=C6)Cl.CN(C)C=O
null
null
C=CC(=O)OCC.CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3cccc(Br)c3)[nH]c(=O)c12>Cl[Pd]([P](C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3)([P](C4=CC=CC=C4)(C5=CC=CC=C5)C6=CC=CC=C6)Cl.CN(C)C=O>CCOC(=O)/C=C/c1cccc(-c2nn3c([C@H]4CC[C@@H](C(C)(C)C)CC4)nc(CC)c3c(=O)[nH]2)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-51044c91d0ff457886ab82df0c68c972
CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3cccc(C#N)c3)[nH]c(=O)c12>>CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3cccc(C(N)=O)c3)[nH]c(=O)c12
ClCCl.C([O-])([O-])=O.[K+].[K+].C(C)(C)(C)[C@H]1CC[C@H](CC1)C1=NC(=C2C(NC(=NN21)C=2C=C(C#N)C=CC2)=O)CC>>C(C)(C)(C)[C@H]1CC[C@H](CC1)C1=NC(=C2C(NC(=NN21)C=2C=C(C(=O)N)C=CC2)=O)CC
[CH3:1][CH2:2][c:3]1[n:4][c:5]([C@H:6]2[CH2:7][CH2:8][C@@H:9]([C:10]([CH3:11])([CH3:12])[CH3:13])[CH2:14][CH2:15]2)[n:16]2[n:17][c:18](-[c:19]3[cH:20][cH:21][cH:22][c:23]([C:24]#[N:25])[cH:27]3)[nH:28][c:29](=[O:30])[c:31]12>>[CH3:1][CH2:2][c:3]1[n:4][c:5]([C@H:6]2[CH2:7][CH2:8][C@@H:9]([C:10]([CH3:11])([CH3:12])[CH3:1...
CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3cccc(C#N)c3)[nH]c(=O)c12
CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3cccc(C(N)=O)c3)[nH]c(=O)c12
null
null
O.C(C)O
Functional Group Addition
Nitrile to amide
538c271df55faf6c40eed3b4a4f85f3f4e5c19a479326ea2f666ed82bd9b2b69
276fda5d5f5a53d66ac109e4f504751b1c2e3eef2b30a60eb746c3377c075030
O=c1[nH]c(-c2ccccc2)nn2c(C3CCCCC3)ncc12
[N;H0;D1;+0:1]#[C;H0;D2;+0:2]-[c:3](:[c:4]):[c:5]>>[NH2;D1;+0:1]-[C;H0;D3;+0:2](=[O;D1;H0:6])-[c:3](:[c:4]):[c:5]
null
[]
null
null
18
HOUR
100 mg (0.25 mmol) cis-3-[7-(4-tert-butylcyclohexyl)-5-ethyl-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl]benzonitrile (Example 40A) are dissolved in 5 ml ethanol and 10 ml water. 342 mg (2.48 mmol) potassium carbonate and 281 mg (2.48 mmol) hydrogene peroxide are added. The reaction mixture is stirred at room te...
10.6084/m9.figshare.5104873.v1
null
Nitrile
Primary amide
null
null
C1CCCCC1.c1ncc2cncn2n1.c1ccccc1
Other
O.C(C)O
null
18
CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3cccc(C#N)c3)[nH]c(=O)c12>O.C(C)O>CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3cccc(C(N)=O)c3)[nH]c(=O)c12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-8989254712ee4cc1a25f2470b71bdd04
CCOC(C)=O.CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3cccc(C#N)c3)[nH]c(=O)c12.[OH-]>>CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3cccc(C(=O)O)c3)[nH]c(=O)c12
C(C)(C)(C)[C@H]1CC[C@H](CC1)C1=NC(=C2C(NC(=NN21)C=2C=C(C#N)C=CC2)=O)CC.[OH-].[Na+].C(C)OC(C)=O>>C(C)(C)(C)[C@H]1CC[C@H](CC1)C1=NC(=C2C(NC(=NN21)C=2C=C(C(=O)O)C=CC2)=O)CC
CCOC(C)=[O:25].N#[C:24][c:23]1[cH:22][cH:21][cH:20][c:19](-[c:18]2[n:17][n:16]3[c:5]([C@H:6]4[CH2:7][CH2:8][C@@H:9]([C:10]([CH3:11])([CH3:12])[CH3:13])[CH2:14][CH2:15]4)[n:4][c:3]([CH2:2][CH3:1])[c:31]3[c:29](=[O:30])[nH:28]2)[cH:27]1.[OH-:26]>>[CH3:1][CH2:2][c:3]1[n:4][c:5]([C@H:6]2[CH2:7][CH2:8][C@@H:9]([C:10]([CH3:1...
CCOC(C)=O.CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3cccc(C#N)c3)[nH]c(=O)c12.[OH-]
CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3cccc(C(=O)O)c3)[nH]c(=O)c12
null
null
Cl
Acylation
OtherReaction
974e60925fd89af1c3b044d933553cce925faa6db18d80fa0703702af6700b36
35145860eafb9e213e05cd391336310346475d6c08ca0007d2df89a15df4c11f
O=c1[nH]c(-c2ccccc2)nn2c(C3CCCCC3)ncc12
C-C-O-C(-C)=[O;H0;D1;+0:1].N#[C;H0;D2;+0:2]-[c:3](:[c:4]):[c:5].[OH-;D0:6]>>[O;H0;D1;+0:1]=[C;H0;D3;+0:2](-[OH;D1;+0:6])-[c:3](:[c:4]):[c:5]
null
[]
95
CELSIUS
3
HOUR
108 mg (0.27 mmol) cis-3-[7-(4-tert-butylcyclohexyl)-5-ethyl-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl]benzonitrile (Example 40A) are dissolved in concentrated hydrochloric acid, and the reaction mixture is stirred at 95° C. for three hours. Sodium hydroxide (10% aqueous solution) (until a pH of 6–7 is achieve...
10.6084/m9.figshare.5104873.v1
null
Ester.Nitrile
Carboxylic acid
null
null
C1CCCCC1.c1ncc2cncn2n1.c1ccccc1
HO-
Cl
95
3
CCOC(C)=O.CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3cccc(C#N)c3)[nH]c(=O)c12.[OH-]>Cl>CCc1nc([C@H]2CC[C@@H](C(C)(C)C)CC2)n2nc(-c3cccc(C(=O)O)c3)[nH]c(=O)c12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4efe20b2dcc24235867d1b924dfb1180
CCc1nc(C2CCCC2)n2nc(-c3cccc([N+](=O)[O-])c3)[nH]c(=O)c12>>CCc1nc(C2CCCC2)n2nc(-c3cccc(N)c3)[nH]c(=O)c12
C1(CCCC1)C1=NC(=C2C(NC(=NN21)C2=CC(=CC=C2)[N+](=O)[O-])=O)CC.[H][H].[H][H]>>NC=1C=C(C=CC1)C1=NN2C(C(N1)=O)=C(N=C2C2CCCC2)CC
O=[N+:19]([O-])[c:18]1[cH:17][cH:16][cH:15][c:14](-[c:13]2[n:12][n:11]3[c:5]([CH:6]4[CH2:7][CH2:8][CH2:9][CH2:10]4)[n:4][c:3]([CH2:2][CH3:1])[c:24]3[c:22](=[O:23])[nH:21]2)[cH:20]1>>[CH3:1][CH2:2][c:3]1[n:4][c:5]([CH:6]2[CH2:7][CH2:8][CH2:9][CH2:10]2)[n:11]2[n:12][c:13](-[c:14]3[cH:15][cH:16][cH:17][c:18]([NH2:19])[cH:...
CCc1nc(C2CCCC2)n2nc(-c3cccc([N+](=O)[O-])c3)[nH]c(=O)c12
CCc1nc(C2CCCC2)n2nc(-c3cccc(N)c3)[nH]c(=O)c12
null
[Pd]
CO
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
O=c1[nH]c(-c2ccccc2)nn2c(C3CCCC3)ncc12
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
null
null
null
null
1.8 g (5.1 mmol) 7-cyclopentyl-5-ethyl-2-(3-nitrophenyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one (Example 21A) are dissolved in 100 ml methanol, and 200 mg palladium (10% on charcoal) are added. The mixture is exposed to an hydrogen atmosphere until no more hydrogen is absorbed. Then the palladium/charcoal is removed by ...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
C1CCCC1.c1ncc2cncn2n1.c1ccccc1
Other
[Pd].CO
null
null
CCc1nc(C2CCCC2)n2nc(-c3cccc([N+](=O)[O-])c3)[nH]c(=O)c12>[Pd].CO>CCc1nc(C2CCCC2)n2nc(-c3cccc(N)c3)[nH]c(=O)c12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3c08076cfb544b0ab431d668be6fd6ed
CC(C)(C)C(=O)Cl.CCc1nc(C2CCCC2)n2nc(-c3cccc(N)c3)[nH]c(=O)c12>>CCc1nc(C2CCCC2)n2nc(-c3cccc(NC(=O)C(C)(C)C)c3)[nH]c(=O)c12
NC=1C=C(C=CC1)C1=NN2C(C(N1)=O)=C(N=C2C2CCCC2)CC.C(C)N(CC)CC.CC(C(=O)Cl)(C)C>>C1(CCCC1)C1=NC(=C2C(NC(=NN21)C=2C=C(C=CC2)NC(C(C)(C)C)=O)=O)CC
Cl[C:20](=[O:21])[C:22]([CH3:23])([CH3:24])[CH3:25].[CH3:1][CH2:2][c:3]1[n:4][c:5]([CH:6]2[CH2:7][CH2:8][CH2:9][CH2:10]2)[n:11]2[n:12][c:13](-[c:14]3[cH:15][cH:16][cH:17][c:18]([NH2:19])[cH:26]3)[nH:27][c:28](=[O:29])[c:30]12>>[CH3:1][CH2:2][c:3]1[n:4][c:5]([CH:6]2[CH2:7][CH2:8][CH2:9][CH2:10]2)[n:11]2[n:12][c:13](-[c:...
CC(C)(C)C(=O)Cl.CCc1nc(C2CCCC2)n2nc(-c3cccc(N)c3)[nH]c(=O)c12
CCc1nc(C2CCCC2)n2nc(-c3cccc(NC(=O)C(C)(C)C)c3)[nH]c(=O)c12
null
null
ClCCl
Acylation
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
38143a4d536201990008fd6f2c68e6571a341d1c367481869fbbbe36cb038937
0e6ae078978e324f714e184b4f72826d4e3bf2d9ab22d6e9f73740af687be16f
O=c1[nH]c(-c2ccccc2)nn2c(C3CCCC3)ncc12
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C;D1;H3:4])(-[C;D1;H3:5])-[C;D1;H3:6].[NH2;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[C;D1;H3:4]-[C:3](-[C;D1;H3:5])(-[C;D1;H3:6])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:7]-[c:8](:[c:9]):[c:10]
null
[]
null
null
2
HOUR
50 mg (0.16 mmol) 2-(3-aminophenyl)-7-cyclopentyl-5-ethylimidazo[5,1-f][1,2,4]-triazin-4(3H)-one (Example 29) and 78 mg (0.77 mmol) triethylamine are dissolved in 4 ml dichloromethane. 37 mg (0.31 mmol) 2,2-dimethylpropanoyl chloride are added dropwise. The mixture is stirred for 2 hours at room temperature and then wa...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amine
Secondary amide
null
null
C1CCCC1.c1ncc2cncn2n1.c1ccccc1
HCl
ClCCl
null
2
CC(C)(C)C(=O)Cl.CCc1nc(C2CCCC2)n2nc(-c3cccc(N)c3)[nH]c(=O)c12>ClCCl>CCc1nc(C2CCCC2)n2nc(-c3cccc(NC(=O)C(C)(C)C)c3)[nH]c(=O)c12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f2177943fabb401aba978188f1d2b8c8
CCc1nc(C2CCCC2)n2nc(-c3cccc(N)c3)[nH]c(=O)c12.O=C(Cl)c1ccccc1>>CCc1nc(C2CCCC2)n2nc(-c3cccc(N(C(=O)c4ccccc4)C(=O)c4ccccc4)c3)[nH]c(=O)c12
NC=1C=C(C=CC1)C1=NN2C(C(N1)=O)=C(N=C2C2CCCC2)CC.C(C1=CC=CC=C1)(=O)Cl>>C(C1=CC=CC=C1)(=O)N(C(C1=CC=CC=C1)=O)C1=CC(=CC=C1)C1=NN2C(C(N1)=O)=C(N=C2C2CCCC2)CC
[CH3:1][CH2:2][c:3]1[n:4][c:5]([CH:6]2[CH2:7][CH2:8][CH2:9][CH2:10]2)[n:11]2[n:12][c:13](-[c:14]3[cH:15][cH:16][cH:17][c:18]([NH2:19])[cH:36]3)[nH:37][c:38](=[O:39])[c:40]12.Cl[C:20](=[O:21])[c:22]1[cH:23][cH:24][cH:25][cH:26][cH:27]1>>[CH3:1][CH2:2][c:3]1[n:4][c:5]([CH:6]2[CH2:7][CH2:8][CH2:9][CH2:10]2)[n:11]2[n:12][c...
CCc1nc(C2CCCC2)n2nc(-c3cccc(N)c3)[nH]c(=O)c12.O=C(Cl)c1ccccc1
CCc1nc(C2CCCC2)n2nc(-c3cccc(N(C(=O)c4ccccc4)C(=O)c4ccccc4)c3)[nH]c(=O)c12
null
null
null
Aromatic Heterocycle Formation
OtherReaction
f3ae2e26e5c36d950e8992dbf8a0d4cd9801e072d869a545bd74b2e75d5c8d9d
62c5d788e8fa1e7e363d67f0f0f1fa483cc214ddb72adc066e5c9da856c4fbfe
O=C(c1ccccc1)N(C(=O)c1ccccc1)c1cccc(-c2nn3c(C4CCCC4)ncc3c(=O)[nH]2)c1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[NH2;D1;+0:6]-[c:7](:[c:8]):[c:9]>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[N;H0;D3;+0:6](-[C:10](=[O;D1;H0:11])-[c:12])-[c:7](:[c:8]):[c:9])-[c:3](:[c:4]):[c:5]
null
[]
null
null
null
null
In analogy to the procedure for Example 31, 50 mg (0.15 mmol) 2-(3-aminophenyl)-7-cyclopentyl-5-ethylimidazo[5,1-f][1,2,4]triazin-4(3H)-one (Example 29), 43 mg (0.31 mmol) benzoyl chloride and proportionate amounts of the other reagents are used. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amine
Substituted dicarboximide
null
c1ccccc1
C1CCCC1.c1ncc2cncn2n1.c1ccccc1.c1ccccc1.c1ccccc1
null
null
null
null
CCc1nc(C2CCCC2)n2nc(-c3cccc(N)c3)[nH]c(=O)c12.O=C(Cl)c1ccccc1>>CCc1nc(C2CCCC2)n2nc(-c3cccc(N(C(=O)c4ccccc4)C(=O)c4ccccc4)c3)[nH]c(=O)c12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3ada23c7cb8648bc9f3e1d83868ffd3c
CCc1nc(C2CCCC2)n2nc(-c3cccc(N)c3)[nH]c(=O)c12.O=Cc1ccccc1>>CCc1nc(C2CCCC2)n2nc(-c3cccc(NCc4ccccc4)c3)[nH]c(=O)c12
NC=1C=C(C=CC1)C1=NN2C(C(N1)=O)=C(N=C2C2CCCC2)CC.C(C1=CC=CC=C1)=O>>C(C1=CC=CC=C1)NC=1C=C(C=CC1)C1=NN2C(C(N1)=O)=C(N=C2C2CCCC2)CC
[CH3:1][CH2:2][c:3]1[n:4][c:5]([CH:6]2[CH2:7][CH2:8][CH2:9][CH2:10]2)[n:11]2[n:12][c:13](-[c:14]3[cH:15][cH:16][cH:17][c:18]([NH2:19])[cH:27]3)[nH:28][c:29](=[O:30])[c:31]12.O=[CH:20][c:21]1[cH:22][cH:23][cH:24][cH:25][cH:26]1>>[CH3:1][CH2:2][c:3]1[n:4][c:5]([CH:6]2[CH2:7][CH2:8][CH2:9][CH2:10]2)[n:11]2[n:12][c:13](-[c...
CCc1nc(C2CCCC2)n2nc(-c3cccc(N)c3)[nH]c(=O)c12.O=Cc1ccccc1
CCc1nc(C2CCCC2)n2nc(-c3cccc(NCc4ccccc4)c3)[nH]c(=O)c12
null
null
null
Heteroatom Alkylation and Arylation
Reductive amination with aldehyde
422be648aea52bce28ccc8fb32ec3178aaa47bbd624f063874619362f075b5f2
7915721a3e395aed85e3c40dc4d725c571a931ac517c6a0da16f2a2b0bb5eac7
O=c1[nH]c(-c2cccc(NCc3ccccc3)c2)nn2c(C3CCCC3)ncc12
O=[CH;D2;+0:1]-[c:2](:[c:3]):[c:4].[NH2;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[c:7]:[c:6](-[NH;D2;+0:5]-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4]):[c:8]
null
[]
null
null
null
null
In analogy to the procedure for Example 8, 100 mg (0.31 mmol) 2-(3-aminophenyl)-7-cyclopentyl-5-ethylimidazo[5,1-f][1,2,4]triazin-4(3H)-one (Example 29), 52 mg (0.49 mmol) benzaldehyde and proportionate amounts of the other reagents are used. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Primary amine
Secondary amine
null
null
C1CCCC1.c1ncc2cncn2n1.c1ccccc1.c1ccccc1
Other
null
null
null
CCc1nc(C2CCCC2)n2nc(-c3cccc(N)c3)[nH]c(=O)c12.O=Cc1ccccc1>>CCc1nc(C2CCCC2)n2nc(-c3cccc(NCc4ccccc4)c3)[nH]c(=O)c12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e3b36a21bf3042018d6e832c2ae48db7
COC(=O)c1ccc(-c2ccccc2C(F)(F)F)cc1[N+](=O)[O-]>>COC(=O)c1ccc(-c2ccccc2C(F)(F)F)cc1N
COC(=O)C1=C(C=C(C=C1)C1=C(C=CC=C1)C(F)(F)F)[N+](=O)[O-].[H][H]>>COC(=O)C1=C(C=C(C=C1)C1=C(C=CC=C1)C(F)(F)F)N
O=[N+:21]([O-])[c:20]1[c:5]([C:3]([O:2][CH3:1])=[O:4])[cH:6][cH:7][c:8](-[c:9]2[cH:10][cH:11][cH:12][cH:13][c:14]2[C:15]([F:16])([F:17])[F:18])[cH:19]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8](-[c:9]2[cH:10][cH:11][cH:12][cH:13][c:14]2[C:15]([F:16])([F:17])[F:18])[cH:19][c:20]1[NH2:21]
COC(=O)c1ccc(-c2ccccc2C(F)(F)F)cc1[N+](=O)[O-]
COC(=O)c1ccc(-c2ccccc2C(F)(F)F)cc1N
null
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1
null
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccc(-c2ccccc2)cc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]-[C:5](-[#8:6])=[O;D1;H0:7]>>[#8:6]-[C:5](=[O;D1;H0:7])-[c:4]:[c:2](-[NH2;D1;+0:1]):[c:3]
null
[]
null
null
18
HOUR
In a Parr apparatus, hydrogenate an ethanolic solution of 3-nitro-2′-trifluoromethyl-biphenyl-4-carboxylic acid methyl ester (5.54 g, 0.0169 mol) under 55 psi of hydrogen using tetrakis(triphenylphosphine)palladium(0) (300 mg). After 18 hours, filter the mixture through celite and concentrate under reduced pressure to ...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccccc1.c1ccccc1
Other
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1
null
18
COC(=O)c1ccc(-c2ccccc2C(F)(F)F)cc1[N+](=O)[O-]>C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1>COC(=O)c1ccc(-c2ccccc2C(F)(F)F)cc1N
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-55ccd850a1ba47d9acc11261c2133a02
COC(=O)c1ccc(-c2ccccc2C(F)(F)F)cc1N.N=CN>>O=c1[nH]cnc2cc(-c3ccccc3C(F)(F)F)ccc12
COC(=O)C1=C(C=C(C=C1)C1=C(C=CC=C1)C(F)(F)F)N.C(C)(=O)O.C(=N)N>>FC(C1=C(C=CC=C1)C1=CC=C2C(NC=NC2=C1)=O)(F)F
CO[C:2](=[O:1])[c:21]1[c:6]([NH2:5])[cH:7][c:8](-[c:9]2[cH:10][cH:11][cH:12][cH:13][c:14]2[C:15]([F:16])([F:17])[F:18])[cH:19][cH:20]1.N[CH:4]=[NH:3]>>[O:1]=[c:2]1[nH:3][cH:4][n:5][c:6]2[cH:7][c:8](-[c:9]3[cH:10][cH:11][cH:12][cH:13][c:14]3[C:15]([F:16])([F:17])[F:18])[cH:19][cH:20][c:21]12
COC(=O)c1ccc(-c2ccccc2C(F)(F)F)cc1N.N=CN
O=c1[nH]cnc2cc(-c3ccccc3C(F)(F)F)ccc12
null
null
COCCO.[OH-].[Na+]
Aromatic Heterocycle Formation
OtherReaction
530017bcdfdaa01ed48948cb6a4af5f6e6064762ac85d2ad3985f28bd32a3b8a
36efa24579e0043fdba8918e78f1d75cb4504837c08d344d01203f5fa64bfaef
O=c1[nH]cnc2cc(-c3ccccc3)ccc12
C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5](-[NH2;D1;+0:6]):[c:7].N-[CH;D2;+0:8]=[NH;D1;+0:9]>>[O;D1;H0:2]=[c;H0;D3;+0:1]1:[nH;D2;+0:9]:[cH;D2;+0:8]:[n;H0;D2;+0:6]:[c:5](:[c:7]):[c:3]:1:[c:4]
null
[]
null
null
null
null
Heat a solution of 3-amino-2′-trifluoromethyl-biphenyl-4-carboxylic acid methyl ester (5.0 g, 0.0169 mol) and formamidine acetate (2.8 g, 0.0203 mol) in 2-methoxyethanol at reflux for 8 hours. Cool the mixture and concentrate under reduced pressure to give a dark oil. Dissolve the residue in 10% NaOH and wash the aqueo...
10.6084/m9.figshare.5104873.v1
null
Ester.Primary amine.Primary amine
null
c1ccccc1
c1ccc2cncnc2c1
c1ccc2cncnc2c1.c1ccccc1
HO-
COCCO.[OH-].[Na+]
null
null
COC(=O)c1ccc(-c2ccccc2C(F)(F)F)cc1N.N=CN>COCCO.[OH-].[Na+]>O=c1[nH]cnc2cc(-c3ccccc3C(F)(F)F)ccc12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-85096be6402a44cfbf3fe7673cde7d26
O=P(Cl)(Cl)Cl.O=c1[nH]cnc2cc(-c3ccccc3C(F)(F)F)ccc12>>FC(F)(F)c1ccccc1-c1ccc2c(Cl)ncnc2c1
FC(C1=C(C=CC=C1)C1=CC=C2C(NC=NC2=C1)=O)(F)F.O=P(Cl)(Cl)Cl>>ClC1=NC=NC2=CC(=CC=C12)C1=C(C=CC=C1)C(F)(F)F
O=P(Cl)(Cl)[Cl:16].O=[c:15]1[c:14]2[cH:13][cH:12][c:11](-[c:10]3[c:5]([C:2]([F:1])([F:3])[F:4])[cH:6][cH:7][cH:8][cH:9]3)[cH:21][c:20]2[n:19][cH:18][nH:17]1>>[F:1][C:2]([F:3])([F:4])[c:5]1[cH:6][cH:7][cH:8][cH:9][c:10]1-[c:11]1[cH:12][cH:13][c:14]2[c:15]([Cl:16])[n:17][cH:18][n:19][c:20]2[cH:21]1
O=P(Cl)(Cl)Cl.O=c1[nH]cnc2cc(-c3ccccc3C(F)(F)F)ccc12
FC(F)(F)c1ccccc1-c1ccc2c(Cl)ncnc2c1
null
null
null
Functional Group Interconversion
OtherReaction
5d38f97f3712b237e9f3fba95a694ccb97b6e400bb6127459a74d91e2bc1ab18
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccc(-c2ccc3cncnc3c2)cc1
Cl-P(-Cl)(=O)-[Cl;H0;D1;+0:1].O=[c;H0;D3;+0:2]1:[nH;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[n;H0;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]
null
[]
null
null
null
null
Reflux a solution of 7-(2-Trifluoromethyl-phenyl)-3H-quinazolin-4-one (1.12 g, 0.0039 mol) in POCl3 for 16 hours. Cool the mixture and concentrate under reduced pressure. Partition the residue between saturated aqueous NaHCO3 and EtOAc. Wash the EtOAc layer once with additional NaHCO3, dry it (Na2SO4), and concentrate ...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccc2cncnc2c1
c1ccc2ncncc2c1
c1ccccc1.c1ccc2ncncc2c1
HCl
null
null
null
O=P(Cl)(Cl)Cl.O=c1[nH]cnc2cc(-c3ccccc3C(F)(F)F)ccc12>>FC(F)(F)c1ccccc1-c1ccc2c(Cl)ncnc2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b14ae749108a4bd3898ed601b3fb77a8
OB(O)c1ccccc1C(F)(F)F.Oc1ccnc2cc(Cl)ccc12>>Oc1ccnc2cc(-c3ccccc3C(F)(F)F)ccc12
C1(CCCCC1)P(C1=C(C=CC=C1)C1=CC=CC=C1)C1CCCCC1.[O-]P(=O)([O-])[O-].[K+].[K+].[K+].ClC1=CC=C2C(=CC=NC2=C1)O.FC(C1=C(C=CC=C1)B(O)O)(F)F>>FC(C1=C(C=CC=C1)C1=CC=C2C(=CC=NC2=C1)O)(F)F
OB(O)[c:9]1[cH:10][cH:11][cH:12][cH:13][c:14]1[C:15]([F:16])([F:17])[F:18].Cl[c:8]1[cH:7][c:6]2[n:5][cH:4][cH:3][c:2]([OH:1])[c:21]2[cH:20][cH:19]1>>[OH:1][c:2]1[cH:3][cH:4][n:5][c:6]2[cH:7][c:8](-[c:9]3[cH:10][cH:11][cH:12][cH:13][c:14]3[C:15]([F:16])([F:17])[F:18])[cH:19][cH:20][c:21]12
OB(O)c1ccccc1C(F)(F)F.Oc1ccnc2cc(Cl)ccc12
Oc1ccnc2cc(-c3ccccc3C(F)(F)F)ccc12
null
C(C)(=O)[O-].[Pd+2].C(C)(=O)[O-]
O.C1(=CC=CC=C1)C.CCOC(=O)C
C-C Coupling
Suzuki coupling with boronic acids
73d3d45d842e591351c81053feb1b3096820b80e5a86db47217e78e2a9707cc8
08d2969413ef1a2cd5b43667268ba178160c7b55545bf48018e31f2b019632ec
c1ccc(-c2ccc3cccnc3c2)cc1
Cl-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[c:4]:[c:5](:[#7;a:6]:[c:7]):[c:8]:1.O-B(-O)-[c;H0;D3;+0:9](:[c:10]:[c:11]):[c:12](-[C:13](-[F;D1;H0:14])(-[F;D1;H0:15])-[F;D1;H0:16]):[c:17]>>[F;D1;H0:14]-[C:13](-[F;D1;H0:15])(-[F;D1;H0:16])-[c:12](:[c:17]):[c;H0;D3;+0:9](-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[c:4]:[c:5](:[#7;a:6]:[c:7]):[c:8]:1...
6.9
[{"value": 6.9, "product": "FC(C1=C(C=CC=C1)C1=CC=C2C(=CC=NC2=C1)O)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Combine 7-chloroquinolin-4-ol (1000 mg, 5.55 mmol,) 2-(trifluoromethyl)phenylboronic acid (1583 mg, 8.33 mmol) and toluene (50 mL), and bubble nitrogen into the solution for 10 minutes. Add palladium acetate (25 mg, 0.11 mmol), 2-(dicyclohexylphosphino)biphenyl (78 mg, 0.22 mmol), and K3PO4 (2353 mg, 11.1 mmol) and hea...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Boronic acid
null
c1ccccc1.c1ccc2ncccc2c1
c1ccc2ncccc2c1.c1ccccc1
c1ccc2ncccc2c1.c1ccccc1
HCl.B
C(C)(=O)[O-].[Pd+2].C(C)(=O)[O-].O.C1(=CC=CC=C1)C.CCOC(=O)C
null
null
OB(O)c1ccccc1C(F)(F)F.Oc1ccnc2cc(Cl)ccc12>C(C)(=O)[O-].[Pd+2].C(C)(=O)[O-].O.C1(=CC=CC=C1)C.CCOC(=O)C>Oc1ccnc2cc(-c3ccccc3C(F)(F)F)ccc12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-25f5926006814ac5acea8cf5bef902fc
O=P(Cl)(Cl)Cl.Oc1ccnc2cc(-c3ccccc3C(F)(F)F)ccc12>>FC(F)(F)c1ccccc1-c1ccc2c(Cl)ccnc2c1
FC(C1=C(C=CC=C1)C1=CC=C2C(=CC=NC2=C1)O)(F)F.O=P(Cl)(Cl)Cl>>ClC1=CC=NC2=CC(=CC=C12)C1=C(C=CC=C1)C(F)(F)F
O=P(Cl)(Cl)[Cl:16].O[c:15]1[c:14]2[cH:13][cH:12][c:11](-[c:10]3[c:5]([C:2]([F:1])([F:3])[F:4])[cH:6][cH:7][cH:8][cH:9]3)[cH:21][c:20]2[n:19][cH:18][cH:17]1>>[F:1][C:2]([F:3])([F:4])[c:5]1[cH:6][cH:7][cH:8][cH:9][c:10]1-[c:11]1[cH:12][cH:13][c:14]2[c:15]([Cl:16])[cH:17][cH:18][n:19][c:20]2[cH:21]1
O=P(Cl)(Cl)Cl.Oc1ccnc2cc(-c3ccccc3C(F)(F)F)ccc12
FC(F)(F)c1ccccc1-c1ccc2c(Cl)ccnc2c1
null
null
null
Functional Group Interconversion
Alcohol to chloride_POCl3_para
27014e1419adc48e7dd5f2024d7f933bb85e42d4ec6c57e509da2884d477d689
e71580a8ffadb7b2717ecd7d68c1d3c0ca161ba5e6a787a49dad5a1359adc993
c1ccc(-c2ccc3cccnc3c2)cc1
Cl-P(-Cl)(=O)-[Cl;H0;D1;+0:1].O-[c;H0;D3;+0:2]1:[c:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[c:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]
null
[]
null
null
null
null
Heat a mixture of 7-(2-trifluoromethyl-phenyl)-quinolin-4-ol (50 mg, 0.17 mmol) in POCl3 (10 mL) at 90° C. for 16 hours. Evaporate the POCl3, and add ice (100 g) followed by careful addition of saturated NaHCO3. Extract with EtOAc, dry (Na2SO4), and evaporate to provide 4-chloro-7-(2-trifluoromethyl-phenyl)-quinoline a...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol
Aromatic halide
c1ccc2ncccc2c1
c1ccc2ncccc2c1
c1ccccc1.c1ccc2ncccc2c1
HCl
null
null
null
O=P(Cl)(Cl)Cl.Oc1ccnc2cc(-c3ccccc3C(F)(F)F)ccc12>>FC(F)(F)c1ccccc1-c1ccc2c(Cl)ccnc2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-7d5f6a01c648471eabeceb164af85f3f
CC(C)(C)c1ccc(N)cc1.FC(F)(F)c1ccccc1-c1ccc2c(Cl)ccnc2c1>>CC(C)(C)c1ccc(Nc2ccnc3cc(-c4ccccc4C(F)(F)F)ccc23)cc1
ClC1=CC=NC2=CC(=CC=C12)C1=C(C=CC=C1)C(F)(F)F.C(C)(C)(C)C1=CC=C(N)C=C1>>C(C)(C)(C)C1=CC=C(C=C1)NC1=CC=NC2=CC(=CC=C12)C1=C(C=CC=C1)C(F)(F)F
[CH3:1][C:2]([CH3:3])([CH3:4])[c:5]1[cH:6][cH:7][c:8]([NH2:9])[cH:30][cH:31]1.Cl[c:10]1[cH:11][cH:12][n:13][c:14]2[cH:15][c:16](-[c:17]3[cH:18][cH:19][cH:20][cH:21][c:22]3[C:23]([F:24])([F:25])[F:26])[cH:27][cH:28][c:29]12>>[CH3:1][C:2]([CH3:3])([CH3:4])[c:5]1[cH:6][cH:7][c:8]([NH:9][c:10]2[cH:11][cH:12][n:13][c:14]3[c...
CC(C)(C)c1ccc(N)cc1.FC(F)(F)c1ccccc1-c1ccc2c(Cl)ccnc2c1
CC(C)(C)c1ccc(Nc2ccnc3cc(-c4ccccc4C(F)(F)F)ccc23)cc1
null
null
CC(C)O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
45e8470a78418ade39424f40732aa5ecf6717a7e5d47830a67429c5970ebd551
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(Nc2ccnc3cc(-c4ccccc4)ccc23)cc1
Cl-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[NH2;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:6]:[c:5]1:[#7;a:4]:[c:3]:[c:2]:[c;H0;D3;+0:1](-[NH;D2;+0:9]-[c:10](:[c:11]):[c:12]):[c:7]:1:[c:8]
null
[]
null
null
null
null
Heat a mixture of 4-chloro-7-(2-trifluoromethyl-phenyl)-quinoline (42 mg, 0.14 mmol) and 4-(tert-butyl)aniline (41 mg, 0.29 mmol) in 2-propanol (10 mL) at reflux for 3 hours. Evaporate the mixture, add 1M NaOH (10 mL), extract twice with EtOAc (10 mL each), dry (Na2SO4), and evaporate to provide the crude product. Puri...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncccc2c1
c1ccc2ncccc2c1
c1ccccc1.c1ccc2ncccc2c1.c1ccccc1
HCl
CC(C)O
null
null
CC(C)(C)c1ccc(N)cc1.FC(F)(F)c1ccccc1-c1ccc2c(Cl)ccnc2c1>CC(C)O>CC(C)(C)c1ccc(Nc2ccnc3cc(-c4ccccc4C(F)(F)F)ccc23)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-5a51a6fbac0844e1938e16615a729bdb
O=[N+]([O-])c1cc(Br)cnc1Br>>N#Cc1ncc(Br)cc1[N+](=O)[O-]
BrC1=NC=C(C=C1[N+](=O)[O-])Br.CN(C(C)=O)C>>BrC=1C=C(C(=NC1)C#N)[N+](=O)[O-]
Br[c:3]1[n:4][cH:5][c:6]([Br:7])[cH:8][c:9]1[N+:10](=[O:11])[O-:12]>>[N:1]#[C:2][c:3]1[n:4][cH:5][c:6]([Br:7])[cH:8][c:9]1[N+:10](=[O:11])[O-:12]
O=[N+]([O-])c1cc(Br)cnc1Br
N#Cc1ncc(Br)cc1[N+](=O)[O-]
null
null
O
Miscellaneous
OtherReaction
8bb970223fb9058022a1c0cc1f9e538de973681a8f3a5dcbab2e4e1d78c06c44
73a96fe5e833259ca394a42f82d6cc2ee7231bcde92d95030d2893b90c3fef76
c1ccncc1
Br-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](-[#7;+:5]):[c:6]>>[#7;+:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[C:7]#[N;D1;H0:8]):[#7;a:2]:[c:3]
null
[]
null
null
null
null
Heat a solution of 2,5-dibromo-3-nitropyridine (1.77 g, 6.3 mmol; Malinowski (1988) Bull. Soc. Chim. Belg. 97:51; see also U.S. Pat. No. 5,801,183) and cuprous cyanide (0.60 g, 6.69 mmol) in N,N-dimethylacetamide (25 mL) at 100° C. for 72 hours. After cooling, dilute the mixture with water (25 mL) and extract twice wit...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
Nitrile
c1ccncc1
c1ccncc1
c1ccncc1
Br-
O
null
null
O=[N+]([O-])c1cc(Br)cnc1Br>O>N#Cc1ncc(Br)cc1[N+](=O)[O-]
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2083691b1f084ed88c88f49ded1090c7
N#Cc1ncc(Br)cc1[N+](=O)[O-]>>N#Cc1ncc(Br)cc1N
BrC=1C=C(C(=NC1)C#N)[N+](=O)[O-].[OH-].[Na+]>>NC=1C(=NC=C(C1)Br)C#N
O=[N+:10]([O-])[c:9]1[c:3]([C:2]#[N:1])[n:4][cH:5][c:6]([Br:7])[cH:8]1>>[N:1]#[C:2][c:3]1[n:4][cH:5][c:6]([Br:7])[cH:8][c:9]1[NH2:10]
N#Cc1ncc(Br)cc1[N+](=O)[O-]
N#Cc1ncc(Br)cc1N
null
null
Cl
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccncc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4](-[C:5]#[N;D1;H0:6]):[#7;a:7]:[c:8]>>[N;D1;H0:6]#[C:5]-[c:4](:[#7;a:7]:[c:8]):[c:2](-[NH2;D1;+0:1]):[c:3]
null
[]
null
null
8
HOUR
Mix 5-bromo-3-nitropyridine-2-carbonitrile (1.5 g, 5.3 mmol) and SnCl2-dihydrate (5.00 g, 26.3 mmol) in concentrated HCl and allow to stir at room temperature overnight. Work up by adding ice and carefully adding 10 M NaOH until basic. Extract twice with Et2O (200 mL), dry (Na2SO4) and evaporate. Purify by silica gel c...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccncc1
Other
Cl
null
8
N#Cc1ncc(Br)cc1[N+](=O)[O-]>Cl>N#Cc1ncc(Br)cc1N
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-6ee57e5de1aa44ac9b53be26be235c4c
CC(C)(C)c1ccc(N)cc1.Clc1nncc2cc(Br)ccc12>>CC(C)(C)c1ccc(Nc2nncc3cc(Br)ccc23)cc1
BrC=1C=C2C=NN=C(C2=CC1)Cl.C(C)(C)(C)C1=CC=C(N)C=C1>>BrC=1C=C2C=NN=C(C2=CC1)NC1=CC=C(C=C1)C(C)(C)C
[CH3:1][C:2]([CH3:3])([CH3:4])[c:5]1[cH:6][cH:7][c:8]([NH2:9])[cH:21][cH:22]1.Cl[c:10]1[n:11][n:12][cH:13][c:14]2[cH:15][c:16]([Br:17])[cH:18][cH:19][c:20]12>>[CH3:1][C:2]([CH3:3])([CH3:4])[c:5]1[cH:6][cH:7][c:8]([NH:9][c:10]2[n:11][n:12][cH:13][c:14]3[cH:15][c:16]([Br:17])[cH:18][cH:19][c:20]23)[cH:21][cH:22]1
CC(C)(C)c1ccc(N)cc1.Clc1nncc2cc(Br)ccc12
CC(C)(C)c1ccc(Nc2nncc3cc(Br)ccc23)cc1
null
null
CC(C)O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
df3bfedad2a7f0f256464ab6dcf71ec93640ec0ccd579b3524f93860b3777b00
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(Nc2nncc3ccccc23)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[#7;a:3]:[c:4]:[c:5]:[c:6]:1:[c:7].[NH2;D1;+0:8]-[c:9](:[c:10]):[c:11]>>[c:7]:[c:6]1:[c:5]:[c:4]:[#7;a:3]:[#7;a:2]:[c;H0;D3;+0:1]:1-[NH;D2;+0:8]-[c:9](:[c:10]):[c:11]
null
[]
null
null
null
null
Heat a mixture of 6-bromo-1-chloro-phthalazine (500 mg, 2.05 mmol) and 4-(tert-butyl)aniline (611 mg, 4.10 mmol) in 2-propanol (10 mL) at reflux for 3 hours. Evaporate the mixture, add 1M NaOH (10 mL), extract twice with EtOAc (10 mL each), dry (Na2SO4), and evaporate to provide the crude product. Purify by silica gel ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2cnncc2c1
c1ccc2cnncc2c1
c1ccccc1.c1ccc2cnncc2c1
HCl
CC(C)O
null
null
CC(C)(C)c1ccc(N)cc1.Clc1nncc2cc(Br)ccc12>CC(C)O>CC(C)(C)c1ccc(Nc2nncc3cc(Br)ccc23)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f05793046f79432d89909773a45ee04d
CC(C)(C)c1ccc(Nc2nncc3cc(Br)ccc23)cc1.OB(O)c1ccccc1C(F)(F)F>>CC(C)(C)c1ccc(Nc2nncc3cc(-c4ccccc4C(F)(F)F)ccc23)cc1
C(=O)([O-])[O-].[Na+].[Na+].BrC=1C=C2C=NN=C(C2=CC1)NC1=CC=C(C=C1)C(C)(C)C.FC(C1=C(C=CC=C1)B(O)O)(F)F>>C(C)(C)(C)C1=CC=C(C=C1)NC1=NN=CC2=CC(=CC=C12)C1=C(C=CC=C1)C(F)(F)F
Br[c:16]1[cH:15][c:14]2[cH:13][n:12][n:11][c:10]([NH:9][c:8]3[cH:7][cH:6][c:5]([C:2]([CH3:1])([CH3:3])[CH3:4])[cH:31][cH:30]3)[c:29]2[cH:28][cH:27]1.OB(O)[c:17]1[cH:18][cH:19][cH:20][cH:21][c:22]1[C:23]([F:24])([F:25])[F:26]>>[CH3:1][C:2]([CH3:3])([CH3:4])[c:5]1[cH:6][cH:7][c:8]([NH:9][c:10]2[n:11][n:12][cH:13][c:14]3[...
CC(C)(C)c1ccc(Nc2nncc3cc(Br)ccc23)cc1.OB(O)c1ccccc1C(F)(F)F
CC(C)(C)c1ccc(Nc2nncc3cc(-c4ccccc4C(F)(F)F)ccc23)cc1
null
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1
O.COCCOC
C-C Coupling
Suzuki coupling with boronic acids
765124a941a4c2fe32bcda035a01876b5b57c8176ac5bdf9422b29a396026af6
08d2969413ef1a2cd5b43667268ba178160c7b55545bf48018e31f2b019632ec
c1ccc(Nc2nncc3cc(-c4ccccc4)ccc23)cc1
Br-[c;H0;D3;+0:1](:[c:2]:[c:3]:[c:4]:[#7;a:5]):[c:6]:[c:7].O-B(-O)-[c;H0;D3;+0:8](:[c:9]:[c:10]):[c:11](-[C:12](-[F;D1;H0:13])(-[F;D1;H0:14])-[F;D1;H0:15]):[c:16]>>[#7;a:5]:[c:4]:[c:3]:[c:2]:[c;H0;D3;+0:1](-[c;H0;D3;+0:8](:[c:9]:[c:10]):[c:11](-[C:12](-[F;D1;H0:13])(-[F;D1;H0:14])-[F;D1;H0:15]):[c:16]):[c:6]:[c:7]
null
[]
null
null
48
HOUR
Combine (6-bromo-phthalazin-1-yl)-(4-tert-butyl-phenyl)-amine (60 mg, 0.19 mmol), 2-(trifluoromethyl)phenyl-boronic acid (50 mg, 0.26 mmol) in 1,2-dimethoxyethane (10 mL) and bubble nitrogen into the mixture for 10 minutes. Add tetrakis(triphenylphosphine)palladium(0) (12 mg, 0.01 mmol) and 2M Na2CO3 (1 mL) and heat at...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Boronic acid
null
c1ccc2cnncc2c1.c1ccccc1
c1ccc2cnncc2c1.c1ccccc1
c1ccccc1.c1ccc2cnncc2c1.c1ccccc1
HBr.B
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.O.COCCOC
null
48
CC(C)(C)c1ccc(Nc2nncc3cc(Br)ccc23)cc1.OB(O)c1ccccc1C(F)(F)F>C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.O.COCCOC>CC(C)(C)c1ccc(Nc2nncc3cc(-c4ccccc4C(F)(F)F)ccc23)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-379f8681ec584b4c8d13c1cdd41f476a
CC(C)(C)Nc1ccccc1>>Nc1ccccc1
C(C)(C)N(CC)C(C)C.C(C)(C)(C)NC1=CC=CC=C1.C(C)(C)(C)C1=CC=C(C=C1)NC=1C2=C(N=C(N1)Cl)N=C(C=C2)C2=C(C=CC=C2)C(F)(F)F>>C(C)(C)(C)C1=CC=C(C=C1)NC=1C2=C(N=C(N1)Cl)N=C(C=C2)C2=C(C=CC=C2)C(F)(F)F.NC2=CC=CC=C2
CC(C)(C)[NH:33][c:34]1[cH:35][cH:36][cH:37][cH:38][cH:39]1>>[NH2:33][c:34]1[cH:35][cH:36][cH:37][cH:38][cH:39]1
CC(C)(C)Nc1ccccc1
Nc1ccccc1
null
null
C(C)#N
Deprotection
Tert-butyl deprotection of amine
943c3301bc8692208363af5a150ec6960d70d9b046717b9510b73482a3b682a4
f6571fb5b7780a2b467937abfba91ba7d787f19d503265f299ff4a25a08963bd
c1ccccc1
C-C(-C)(-C)-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
80
CELSIUS
null
null
To a mixture of diisopropylethylamine (260 mg, 2.0 mmol) in acetonitrile (5 mL), add t-butylaniline (124 mg, 1.0 mmol) followed by (4-tert-Butyl-phenyl)-[2-chloro-7-(2-trifluoromethyl-phenyl)-pyrido[2,3-d]pyrimidin-4-yl]-amine (310 mg, 1.0 mmol). Heat the mixture to 80° C. for six hours. Evaporate the solvent, and part...
10.6084/m9.figshare.5104873.v1
null
Secondary amine
Primary amine
null
null
c1ccccc1
Other
C(C)#N
80
null
CC(C)(C)Nc1ccccc1>C(C)#N>Nc1ccccc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4e3a059aa84b42eca801680bf25c1ced
O=P(Cl)(Cl)Cl.O=c1[nH]cnc2cc(Br)ccc12>>Clc1ncnc2cc(Br)ccc12
BrC1=CC=C2C(NC=NC2=C1)=O.O=P(Cl)(Cl)Cl>>BrC1=CC=C2C(=NC=NC2=C1)Cl
O=P(Cl)(Cl)[Cl:1].O=[c:2]1[nH:3][cH:4][n:5][c:6]2[cH:7][c:8]([Br:9])[cH:10][cH:11][c:12]12>>[Cl:1][c:2]1[n:3][cH:4][n:5][c:6]2[cH:7][c:8]([Br:9])[cH:10][cH:11][c:12]12
O=P(Cl)(Cl)Cl.O=c1[nH]cnc2cc(Br)ccc12
Clc1ncnc2cc(Br)ccc12
null
null
null
Functional Group Interconversion
OtherReaction
5d38f97f3712b237e9f3fba95a694ccb97b6e400bb6127459a74d91e2bc1ab18
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccc2ncncc2c1
Cl-P(-Cl)(=O)-[Cl;H0;D1;+0:1].O=[c;H0;D3;+0:2]1:[nH;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[n;H0;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]
null
[]
null
null
null
null
Reflux a solution of 7-bromo-3H-quinazolin-4-one (1.24 g, 0.0055 mol) in POCl3 for 3.5 h. Remove the excess POCl3 under reduced pressure and partition the residue between EtOAc and saturated aqueous NaHCO3. Dry the EtOAc layer and remove the solvent under reduced pressure to give 7-bromo-4-chloro-quinazoline as a yello...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccc2cncnc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1
HCl
null
null
null
O=P(Cl)(Cl)Cl.O=c1[nH]cnc2cc(Br)ccc12>>Clc1ncnc2cc(Br)ccc12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-21e4402921fa4633ac07f6e8ca557001
Clc1ncnc2cc(Br)ccc12.Nc1ccc(C(F)(F)F)cn1>>FC(F)(F)c1ccc(Nc2ncnc3cc(Br)ccc23)nc1
BrC1=CC=C2C(=NC=NC2=C1)Cl.NC1=NC=C(C=C1)C(F)(F)F>>BrC1=CC=C2C(=NC=NC2=C1)NC1=NC=C(C=C1)C(F)(F)F
Cl[c:10]1[n:11][cH:12][n:13][c:14]2[cH:15][c:16]([Br:17])[cH:18][cH:19][c:20]12.[F:1][C:2]([F:3])([F:4])[c:5]1[cH:6][cH:7][c:8]([NH2:9])[n:21][cH:22]1>>[F:1][C:2]([F:3])([F:4])[c:5]1[cH:6][cH:7][c:8]([NH:9][c:10]2[n:11][cH:12][n:13][c:14]3[cH:15][c:16]([Br:17])[cH:18][cH:19][c:20]23)[n:21][cH:22]1
Clc1ncnc2cc(Br)ccc12.Nc1ccc(C(F)(F)F)cn1
FC(F)(F)c1ccc(Nc2ncnc3cc(Br)ccc23)nc1
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(Nc2ncnc3ccccc23)nc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[NH2;D1;+0:9]-[c:10](:[c:11]):[#7;a:12]:[c:13]>>[c:6]:[c:5]1:[#7;a:4]:[c:3]:[#7;a:2]:[c;H0;D3;+0:1](-[NH;D2;+0:9]-[c:10](:[c:11]):[#7;a:12]:[c:13]):[c:7]:1:[c:8]
null
[]
null
null
null
null
Heat a mixture of 7-bromo-4-chloro-quinazoline (200 mg, 0.821 mmol) and 2-amino-5-trifluoromethyl-pyridine (239 mg, 1.48 mmol) at 230° C. for 2 minutes. Cool and partition the solid residue between EtOAc and 10% NaOH. Dry the EtOAc layer (Na2SO4), remove the solvent under reduced pressure, and purify via flash chromato...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccncc1.c1ccc2ncncc2c1
HCl
null
null
null
Clc1ncnc2cc(Br)ccc12.Nc1ccc(C(F)(F)F)cn1>>FC(F)(F)c1ccc(Nc2ncnc3cc(Br)ccc23)nc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-6380d983a4184ff791f58c0af08cb0a2
CCC[CH2][Sn]([Cl])([CH2]CCC)[CH2]CCC.Fc1cccnc1Br>>CCC[CH2][Sn]([CH2]CCC)([CH2]CCC)[c]1ncccc1F
C(CCC)[Sn](CCCC)(CCCC)Cl.BrC1=NC=CC=C1F.C(CCC)[Li]>>FC=1C(=NC=CC1)[Sn](CCCC)(CCCC)CCCC
[Cl][Sn:5]([CH2:4][CH2:3][CH2:2][CH3:1])([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:10][CH2:11][CH2:12][CH3:13].Br[c:14]1[n:15][cH:16][cH:17][cH:18][c:19]1[F:20]>>[CH3:1][CH2:2][CH2:3][CH2:4][Sn:5]([CH2:6][CH2:7][CH2:8][CH3:9])([CH2:10][CH2:11][CH2:12][CH3:13])[c:14]1[n:15][cH:16][cH:17][cH:18][c:19]1[F:20]
CCC[CH2][Sn]([Cl])([CH2]CCC)[CH2]CCC.Fc1cccnc1Br
CCC[CH2][Sn]([CH2]CCC)([CH2]CCC)[c]1ncccc1F
null
null
C1CCOC1
Functional Group Interconversion
OtherReaction
595ac0abb5e92435d058c6ee48fc895ec9c292bdbe417f57a54b9f065eff0354
d9bf9bd3fc00efb5d713d9ac7f168986c2c94f1f455d32bdc9901567c1014c76
c1ccncc1
Br-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](-[F;D1;H0:5]):[c:6].[C:7]-[C:8]-[Sn;H0;D4;+0:9](-[Cl])(-[C:10]-[C:11])-[C:12]-[C:13]>>[C:7]-[C:8]-[Sn;H0;D4;+0:9](-[C:10]-[C:11])(-[C:12]-[C:13])-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](-[F;D1;H0:5]):[c:6]
null
[]
-78
CELSIUS
1.5
HOUR
Cool a solution of 2-bromo-3-fluoro-pyridine (542 mg, 3.08 mmol) in dry THF to −78° C. using a dry ice acetone bath. Add n-butyl-lithium (1.6 M in THF, 2.0 mL) to the reaction mixture dropwise via syringe over a 20 minute period. After stirring for 1.5 hours at −78° C., add tributyltin chloride slowly via syringe and r...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Tin
Tin
c1ccncc1
c1ccncc1
c1ccncc1
Br-
C1CCOC1
-78
1.5
CCC[CH2][Sn]([Cl])([CH2]CCC)[CH2]CCC.Fc1cccnc1Br>C1CCOC1>CCC[CH2][Sn]([CH2]CCC)([CH2]CCC)[c]1ncccc1F
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4080763d33fc4969b23659b3cd2ed48e
O=[N+]([O-])c1cc(Br)ccc1Br>>N#Cc1ccc(Br)cc1[N+](=O)[O-]
BrC1=C(C=C(C=C1)Br)[N+](=O)[O-].C(#N)[Cu]>>BrC1=CC(=C(C#N)C=C1)[N+](=O)[O-]
Br[c:3]1[cH:4][cH:5][c:6]([Br:7])[cH:8][c:9]1[N+:10](=[O:11])[O-:12]>>[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([Br:7])[cH:8][c:9]1[N+:10](=[O:11])[O-:12]
O=[N+]([O-])c1cc(Br)ccc1Br
N#Cc1ccc(Br)cc1[N+](=O)[O-]
null
null
CC(=O)N(C)C.CCOC(=O)C
Miscellaneous
OtherReaction
3ae4da8b7f110de99cf8afc091b6f0c8540050148e425770f8030bce1480042c
73a96fe5e833259ca394a42f82d6cc2ee7231bcde92d95030d2893b90c3fef76
c1ccccc1
Br-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[#7;+:5]):[c:6]>>[#7;+:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[C:7]#[N;D1;H0:8]):[c:2]:[c:3]
null
[]
null
null
null
null
Stir the mixture of 1,4-dibromo-2-nitro-benzene (3.56 mmol)and CuCN (3.74 mmol) in DMA (4 ml) at 100° C. for 5hours. Cool to room temperature, dilute with EtOAc, filter through celite, wash the organic layer with brine, dry over Na2SO4, and concentrate under vacuum. Purify the residue by flash chromatography (4:1 hexan...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
Nitrile
c1ccccc1
c1ccccc1
c1ccccc1
Br-
CC(=O)N(C)C.CCOC(=O)C
null
null
O=[N+]([O-])c1cc(Br)ccc1Br>CC(=O)N(C)C.CCOC(=O)C>N#Cc1ccc(Br)cc1[N+](=O)[O-]
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-41e29dcecaa84db69b632fdb529c9fb7
N#Cc1ccc(Br)cc1[N+](=O)[O-]>>N#Cc1ccc(Br)cc1N
BrC1=CC(=C(C#N)C=C1)[N+](=O)[O-].[OH-].[Na+]>>NC1=C(C#N)C=CC(=C1)Br
O=[N+:10]([O-])[c:9]1[c:3]([C:2]#[N:1])[cH:4][cH:5][c:6]([Br:7])[cH:8]1>>[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([Br:7])[cH:8][c:9]1[NH2:10]
N#Cc1ccc(Br)cc1[N+](=O)[O-]
N#Cc1ccc(Br)cc1N
null
null
Cl
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]
null
[]
null
null
null
null
To a suspension of 4-bromo-2-nitro-benzonitrile (2.60 g, 0.0115 mol) in 12N HCl at 0° C., add SnCl2-2H2O portionwise. As the reaction is stirred vigorously, a white precipitate will form. After 1 h add ice to the reaction vessel followed by 10N NaOH until the solution is basic. Extract the aqueous mixture with ether (2...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccccc1
Other
Cl
null
null
N#Cc1ccc(Br)cc1[N+](=O)[O-]>Cl>N#Cc1ccc(Br)cc1N
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-644bf33342364541a0db4fab617e76e7
N#Cc1ccc(Br)cc1N>>O=c1[nH]cnc2cc(Br)ccc12
[OH-].[Na+].NC1=C(C#N)C=CC(=C1)Br.C(C)(=O)[O-].[Na+]>>BrC1=CC=C2C(NC=NC2=C1)=O
[C:2](#[N:3])[c:12]1[c:6]([NH2:5])[cH:7][c:8]([Br:9])[cH:10][cH:11]1>>[O:1]=[c:2]1[nH:3][cH:4][n:5][c:6]2[cH:7][c:8]([Br:9])[cH:10][cH:11][c:12]12
N#Cc1ccc(Br)cc1N
O=c1[nH]cnc2cc(Br)ccc12
null
null
C(=O)O
Aromatic Heterocycle Formation
OtherReaction
5d271e61807d16bbd3b0249b3cad4800dd1a5c4c451f2dd66ecf5447cbc2c902
7e3cbeb103ea1acdb1099adcfd389a4cbc40c9251b7e8442079d7b87a6dddf23
O=c1[nH]cnc2ccccc12
[N;H0;D1;+0:1]#[C;H0;D2;+0:2]-[c:3](:[c:4]):[c:5](-[NH2;D1;+0:6]):[c:7]>>[O;D1;H0:8]=[c;H0;D3;+0:2]1:[nH;D2;+0:1]:[c:9]:[n;H0;D2;+0:6]:[c:5](:[c:7]):[c:3]:1:[c:4]
null
[]
null
null
1
HOUR
To a solution of 2-amino-4-bromo-benzonitrile (550 mg, 2.79 mmol) in formic acid, add sodium acetate (435 mg, 5.30 mmol) in one portion. Reflux the reaction mixture for 16 h then remove the formic acid under reduced pressure to give a solid. Add 20% aqueous NaOH and stir for 1 hour. Remove the undissolved solids via fi...
10.6084/m9.figshare.5104873.v1
null
Nitrile.Primary amine
null
c1ccccc1
c1ccc2cncnc2c1
c1ccc2cncnc2c1
Other
C(=O)O
null
1
N#Cc1ccc(Br)cc1N>C(=O)O>O=c1[nH]cnc2cc(Br)ccc12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-89f287ff532043e496e44917243ee117
CCC[CH2][Sn]([CH2]CCC)([CH2]CCC)[c]1ccccn1.O=c1[nH]cnc2cc(Br)ccc12>>O=c1[nH]cnc2cc(-c3ccccn3)ccc12
BrC1=CC=C2C(NC=NC2=C1)=O.C(CCC)[Sn](C1=NC=CC=C1)(CCCC)CCCC>>N1=C(C=CC=C1)C1=CC=C2C(NC=NC2=C1)=O
CCC[CH2][Sn]([CH2]CCC)([CH2]CCC)[c:9]1[cH:10][cH:11][cH:12][cH:13][n:14]1.Br[c:8]1[cH:7][c:6]2[n:5][cH:4][nH:3][c:2](=[O:1])[c:17]2[cH:16][cH:15]1>>[O:1]=[c:2]1[nH:3][cH:4][n:5][c:6]2[cH:7][c:8](-[c:9]3[cH:10][cH:11][cH:12][cH:13][n:14]3)[cH:15][cH:16][c:17]12
CCC[CH2][Sn]([CH2]CCC)([CH2]CCC)[c]1ccccn1.O=c1[nH]cnc2cc(Br)ccc12
O=c1[nH]cnc2cc(-c3ccccn3)ccc12
null
[Pd].C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1
C1(=CC=CC=C1)C.O1CCOCC1
C-C Coupling
Stille reaction_aryl
1ad2daad2d66c7e83cb253b81bfefe414ab612665cdcf7bedd9a2df9ae159cf2
db27eeefac0475c6d74fa10b3167e95a61caaae74e8bbafd45892452c0c3d4d6
O=c1[nH]cnc2cc(-c3ccccn3)ccc12
Br-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[c:4]2:[c:5]:[#7;a:6]:[c:7]:[#7;a:8]:[c:9]:2:[c:10]:1.C-C-C-[CH2]-[Sn](-[CH2]-C-C-C)(-[CH2]-C-C-C)-[c;H0;D3;+0:11](:[#7;a:12]:[c:13]):[c:14]:[c:15]>>[c:15]:[c:14]:[c;H0;D3;+0:11](-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[c:4]2:[c:5]:[#7;a:6]:[c:7]:[#7;a:8]:[c:9]:2:[c:10]:1):[#7;a:12]:[c:13]
null
[]
115
CELSIUS
16
HOUR
To a solution of 7-bromo-3H-quinazolin-4-one (100 mg, 0.444 mmol) in toluene/dioxane (3:1), add 2-tributylstannanyl-pyridine (162 mg, 0.444 mmol) followed by tetrakis-(triphenylphosphine)-palladium(0) (26 mg, 0.022 mmol). Bubble dry nitrogen through the solution for 10 minutes then heat the stirring solution to 115° C....
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Tin
null
c1ccncc1.c1ccc2cncnc2c1
c1ccc2cncnc2c1.c1ccncc1
c1ccc2cncnc2c1.c1ccncc1
HBr.Sn
[Pd].C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)C.O1CCOCC1
115
16
CCC[CH2][Sn]([CH2]CCC)([CH2]CCC)[c]1ccccn1.O=c1[nH]cnc2cc(Br)ccc12>[Pd].C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)C.O1CCOCC1>O=c1[nH]cnc2cc(-c3ccccn3)ccc12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4e8cb0995cf849da806203796dbca3c7
FC(F)(F)c1cccnc1-c1ccc(Br)cc1.O=[N+]([O-])O>>O=[N+]([O-])c1cc(-c2ncccc2C(F)(F)F)ccc1Br
BrC1=CC=C(C=C1)C1=NC=CC=C1C(F)(F)F.[N+](=O)(O)[O-]>>BrC1=C(C=C(C=C1)C1=NC=CC=C1C(F)(F)F)[N+](=O)[O-]
[cH:4]1[cH:5][c:6](-[c:7]2[n:8][cH:9][cH:10][cH:11][c:12]2[C:13]([F:14])([F:15])[F:16])[cH:17][cH:18][c:19]1[Br:20].O[N+:2](=[O:1])[O-:3]>>[O:1]=[N+:2]([O-:3])[c:4]1[cH:5][c:6](-[c:7]2[n:8][cH:9][cH:10][cH:11][c:12]2[C:13]([F:14])([F:15])[F:16])[cH:17][cH:18][c:19]1[Br:20]
FC(F)(F)c1cccnc1-c1ccc(Br)cc1.O=[N+]([O-])O
O=[N+]([O-])c1cc(-c2ncccc2C(F)(F)F)ccc1Br
null
null
OS(=O)(=O)O
Functional Group Addition
Aromatic nitration with HNO3
53848b8b2bb4e867226e49db2e60519b24be9379900e3ad7c56af54fe8fde7a5
ddce49825c02b8965f10c8d99e3c841d26e1f136da6037b417c09313e6d73097
c1ccc(-c2ccccn2)cc1
O-[N+;H0;D3:1](-[O;-;D1;H0:2])=[O;D1;H0:3].[Br;D1;H0:4]-[c:5](:[c:6]):[cH;D2;+0:7]:[c:8]:[c:9]>>[Br;D1;H0:4]-[c:5](:[c:6]):[c;H0;D3;+0:7](-[N+;H0;D3:1](-[O;-;D1;H0:2])=[O;D1;H0:3]):[c:8]:[c:9]
null
[]
null
null
30
MINUTE
To a solution of 2-(4-bromophenyl)-3-(trifluoromethyl)-pyridine (0.93 mmol) in H2SO4 (4 mL) cautiously add fuming HNO3 (2 ml). Stir the mixture 30 minutes at room temperature. Pour the mixture onto ice-water (20 mL) and collect the precipitate. Dissolve the precipitate in EtOAc and neutralize with saturated NaHCO3, dry...
10.6084/m9.figshare.5104873.v1
null
Nitrate
Nitro group
c1ccccc1
c1ccccc1
c1ccccc1.c1ccncc1
HO-
OS(=O)(=O)O
null
0.5
FC(F)(F)c1cccnc1-c1ccc(Br)cc1.O=[N+]([O-])O>OS(=O)(=O)O>O=[N+]([O-])c1cc(-c2ncccc2C(F)(F)F)ccc1Br
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d65313b8e7bb46489d82036d77557d52
O=[N+]([O-])c1cc(-c2ncccc2C(F)(F)F)ccc1Br>>N#Cc1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
BrC1=C(C=C(C=C1)C1=NC=CC=C1C(F)(F)F)[N+](=O)[O-].C(#N)[Cu]>>[N+](=O)([O-])C1=C(C#N)C=CC(=C1)C1=NC=CC=C1C(F)(F)F
Br[c:3]1[cH:4][cH:5][c:6](-[c:7]2[n:8][cH:9][cH:10][cH:11][c:12]2[C:13]([F:14])([F:15])[F:16])[cH:17][c:18]1[N+:19](=[O:20])[O-:21]>>[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6](-[c:7]2[n:8][cH:9][cH:10][cH:11][c:12]2[C:13]([F:14])([F:15])[F:16])[cH:17][c:18]1[N+:19](=[O:20])[O-:21]
O=[N+]([O-])c1cc(-c2ncccc2C(F)(F)F)ccc1Br
N#Cc1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
null
null
CC(=O)N(C)C.CCOC(=O)C
Miscellaneous
OtherReaction
3ae4da8b7f110de99cf8afc091b6f0c8540050148e425770f8030bce1480042c
73a96fe5e833259ca394a42f82d6cc2ee7231bcde92d95030d2893b90c3fef76
c1ccc(-c2ccccn2)cc1
Br-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[#7;+:5]):[c:6]>>[#7;+:5]-[c:4](:[c:6]):[c;H0;D3;+0:1](-[C:7]#[N;D1;H0:8]):[c:2]:[c:3]
null
[]
110
CELSIUS
4
HOUR
To a solution of 2-(4-bromo-3-nitro-phenyl)-3-(trifluoromethyl)-pyridine (0.55 mmol) in DMA (4 mL) add CuCN (0.60 mmol). Stir the mixture 4 hours at 110° C. Cool to room temperature, dilute with 20 ml of EtOAc, and filter through celite pad. Wash the filtrated with brine, dry over Na2SO4, concentrate under vacuum, and ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
Nitrile
c1ccccc1
c1ccccc1
c1ccccc1.c1ccncc1
Br-
CC(=O)N(C)C.CCOC(=O)C
110
4
O=[N+]([O-])c1cc(-c2ncccc2C(F)(F)F)ccc1Br>CC(=O)N(C)C.CCOC(=O)C>N#Cc1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-20d9af898f4c46f19487c1a42313c410
N#Cc1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]>>N#Cc1ccc(-c2ncccc2C(F)(F)F)cc1N
[OH-].[Na+].[N+](=O)([O-])C1=C(C#N)C=CC(=C1)C1=NC=CC=C1C(F)(F)F.Cl[Sn]Cl>>NC1=C(C#N)C=CC(=C1)C1=NC=CC=C1C(F)(F)F
O=[N+:19]([O-])[c:18]1[c:3]([C:2]#[N:1])[cH:4][cH:5][c:6](-[c:7]2[n:8][cH:9][cH:10][cH:11][c:12]2[C:13]([F:14])([F:15])[F:16])[cH:17]1>>[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6](-[c:7]2[n:8][cH:9][cH:10][cH:11][c:12]2[C:13]([F:14])([F:15])[F:16])[cH:17][c:18]1[NH2:19]
N#Cc1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
N#Cc1ccc(-c2ncccc2C(F)(F)F)cc1N
null
null
Cl
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccc(-c2ccccn2)cc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
null
null
2
HOUR
To an ice-water cooled solution of 2-nitro-4-(3-trifluoromethyl-pyridin-2-yl)-benzonitrile (0.44 mmol) in conc. HCl (6 mL) add SnCl2 (1.457 mmol). Stir the mixture 2 h at room temperature. neutralize with NaOH, extract with EtOAc, dry over Na2SO4, and concentrate under vacuum. Purify the residue by flash chromatography...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccccc1.c1ccncc1
Other
Cl
null
2
N#Cc1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]>Cl>N#Cc1ccc(-c2ncccc2C(F)(F)F)cc1N
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-59c0121a94384cc9816e0179000b2cbe
O=P(Cl)(Cl)Cl.Oc1ncnc2cc(-c3ncccc3C(F)(F)F)ccc12>>FC(F)(F)c1cccnc1-c1ccc2c(Cl)ncnc2c1
FC(C=1C(=NC=CC1)C1=CC=C2C(=NC=NC2=C1)O)(F)F.O=P(Cl)(Cl)Cl>>ClC1=NC=NC2=CC(=CC=C12)C1=NC=CC=C1C(F)(F)F
O=P(Cl)(Cl)[Cl:16].O[c:15]1[c:14]2[cH:13][cH:12][c:11](-[c:10]3[c:5]([C:2]([F:1])([F:3])[F:4])[cH:6][cH:7][cH:8][n:9]3)[cH:21][c:20]2[n:19][cH:18][n:17]1>>[F:1][C:2]([F:3])([F:4])[c:5]1[cH:6][cH:7][cH:8][n:9][c:10]1-[c:11]1[cH:12][cH:13][c:14]2[c:15]([Cl:16])[n:17][cH:18][n:19][c:20]2[cH:21]1
O=P(Cl)(Cl)Cl.Oc1ncnc2cc(-c3ncccc3C(F)(F)F)ccc12
FC(F)(F)c1cccnc1-c1ccc2c(Cl)ncnc2c1
null
null
null
Functional Group Interconversion
Alcohol to chloride_POCl3_ortho
b0b0f8b7642d018e3b261231985ddd65d16d4d42cce7aa11791e49c826337b90
e71580a8ffadb7b2717ecd7d68c1d3c0ca161ba5e6a787a49dad5a1359adc993
c1ccc(-c2ccc3cncnc3c2)nc1
Cl-P(-Cl)(=O)-[Cl;H0;D1;+0:1].O-[c;H0;D3;+0:2]1:[#7;a:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[#7;a:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]
null
[]
null
null
null
null
Reflux 7-(3-trifluoromethyl-pyridin-2-yl)-quinazolin-4-ol (0.38 mmol) for 18 hours in POCl3 (5 mL). Evaporate the solvent in vacuo, then carefully neutralize with saturated NaHCO3, and extract with EtOAc. Dry over Na2SO4, concentrate under vacuum to obtain 4-chloro-7-(3-trifluoromethyl-pyridin-2-yl)-quinazoline. Condit...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol
Aromatic halide
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccncc1.c1ccc2ncncc2c1
HCl
null
null
null
O=P(Cl)(Cl)Cl.Oc1ncnc2cc(-c3ncccc3C(F)(F)F)ccc12>>FC(F)(F)c1cccnc1-c1ccc2c(Cl)ncnc2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d720991a8abf4ff597f1a39c481956a4
N#Cc1ccc(-c2ncccc2C(F)(F)F)cc1N.[OH-]>>NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N
NC1=C(C#N)C=CC(=C1)C1=NC=CC=C1C(F)(F)F.[OH-].[Na+]>>NC1=C(C(=O)N)C=CC(=C1)C1=NC=CC=C1C(F)(F)F
[N:1]#[C:2][c:4]1[cH:5][cH:6][c:7](-[c:8]2[n:9][cH:10][cH:11][cH:12][c:13]2[C:14]([F:15])([F:16])[F:17])[cH:18][c:19]1[NH2:20].[OH-:3]>>[NH2:1][C:2](=[O:3])[c:4]1[cH:5][cH:6][c:7](-[c:8]2[n:9][cH:10][cH:11][cH:12][c:13]2[C:14]([F:15])([F:16])[F:17])[cH:18][c:19]1[NH2:20]
N#Cc1ccc(-c2ncccc2C(F)(F)F)cc1N.[OH-]
NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N
null
null
OS(=O)(=O)O
Heteroatom Alkylation and Arylation
OtherReaction
1d1793919e847ed86dcb16487e62464531560dbf4782f9a5875bfe7e0477a3ec
d6f9d146e8ef95e62f1a3ab55a7e3b4ceec8856a5f71b6dccd4ad850f945b658
c1ccc(-c2ccccn2)cc1
[N;H0;D1;+0:1]#[C;H0;D2;+0:2]-[c:3](:[c:4]):[c:5].[OH-;D0:6]>>[NH2;D1;+0:1]-[C;H0;D3;+0:2](=[O;H0;D1;+0:6])-[c:3](:[c:4]):[c:5]
null
[]
null
null
null
null
Stir a mixture of 2-amino-4(3-trifluoromethyl-pyridin-2-yl)-benzo-nitrile (0.50 mmol) in 70% H2SO4 (10 ml) at 110° C. for 1 hour. Cool to room temperature, neutralize with NaOH, extract with EtOAc, dry over Na2SO4, and concentrate under vacuum. Purify the residue by flash chromatography (3:2 hexanes/EtOAc) to give 2-am...
10.6084/m9.figshare.5104873.v1
null
Nitrile
Primary amide
null
null
c1ccccc1.c1ccncc1
null
OS(=O)(=O)O
null
null
N#Cc1ccc(-c2ncccc2C(F)(F)F)cc1N.[OH-]>OS(=O)(=O)O>NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-dad51120f4da48c1b3c59053ef01c1a9
CC(=O)Cl.NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N>>CC(=O)Nc1cc(-c2ncccc2C(F)(F)F)ccc1C(N)=O
NC1=C(C(=O)N)C=CC(=C1)C1=NC=CC=C1C(F)(F)F.N1=CC=CC=C1.C(C)(=O)Cl>>C(C)(=O)NC1=C(C(=O)N)C=CC(=C1)C1=NC=CC=C1C(F)(F)F
Cl[C:2]([CH3:1])=[O:3].[NH2:4][c:5]1[cH:6][c:7](-[c:8]2[n:9][cH:10][cH:11][cH:12][c:13]2[C:14]([F:15])([F:16])[F:17])[cH:18][cH:19][c:20]1[C:21]([NH2:22])=[O:23]>>[CH3:1][C:2](=[O:3])[NH:4][c:5]1[cH:6][c:7](-[c:8]2[n:9][cH:10][cH:11][cH:12][c:13]2[C:14]([F:15])([F:16])[F:17])[cH:18][cH:19][c:20]1[C:21]([NH2:22])=[O:23]
CC(=O)Cl.NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N
CC(=O)Nc1cc(-c2ncccc2C(F)(F)F)ccc1C(N)=O
null
null
C1CCOC1
Acylation
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
38143a4d536201990008fd6f2c68e6571a341d1c367481869fbbbe36cb038937
0e6ae078978e324f714e184b4f72826d4e3bf2d9ab22d6e9f73740af687be16f
c1ccc(-c2ccccn2)cc1
Cl-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[N;D1;H2:4]-[C:5](=[O;D1;H0:6])-[c:7]:[c:8](-[NH2;D1;+0:9]):[c:10]>>[C;D1;H3:2]-[C;H0;D3;+0:1](=[O;D1;H0:3])-[NH;D2;+0:9]-[c:8](:[c:10]):[c:7]-[C:5](-[N;D1;H2:4])=[O;D1;H0:6]
null
[]
null
null
10
MINUTE
To a solution of 2-amino-4-(3-trifluoromethyl-pyridin-2-yl)-benzamide (0.5 mmol) and pyridine (0.55 mmol) in THF (5 ml) add acetyl chloride (0.55 mmol). Stir the mixture 10 minutes at room temperature. Concentrate under vacuum, extract with EtOAc, wash with brine, dry over Na2SO4, and concentrate under vacuum. Triturat...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccncc1
HCl
C1CCOC1
null
0.166667
CC(=O)Cl.NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N>C1CCOC1>CC(=O)Nc1cc(-c2ncccc2C(F)(F)F)ccc1C(N)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f16507baa8324bfd8e8a7be323aad471
CC(=O)Nc1cc(-c2ncccc2C(F)(F)F)ccc1C(N)=O>>Cc1nc(O)c2ccc(-c3ncccc3C(F)(F)F)cc2n1
C(C)(=O)NC1=C(C(=O)N)C=CC(=C1)C1=NC=CC=C1C(F)(F)F>>CC1=NC2=CC(=CC=C2C(=N1)O)C1=NC=CC=C1C(F)(F)F
O=[C:2]([CH3:1])[NH:22][c:21]1[c:6]([C:4]([NH2:3])=[O:5])[cH:7][cH:8][c:9](-[c:10]2[n:11][cH:12][cH:13][cH:14][c:15]2[C:16]([F:17])([F:18])[F:19])[cH:20]1>>[CH3:1][c:2]1[n:3][c:4]([OH:5])[c:6]2[cH:7][cH:8][c:9](-[c:10]3[n:11][cH:12][cH:13][cH:14][c:15]3[C:16]([F:17])([F:18])[F:19])[cH:20][c:21]2[n:22]1
CC(=O)Nc1cc(-c2ncccc2C(F)(F)F)ccc1C(N)=O
Cc1nc(O)c2ccc(-c3ncccc3C(F)(F)F)cc2n1
null
null
[OH-].[Na+]
Aromatic Heterocycle Formation
OtherReaction
2f062f807c82221b053d8e69b1222d7c6a9c8bd3dfea25f1341bdd9b6ded7751
b315f5051658d018f21ccded5f298d0b6fc5d41ed682f748b2c9a0a662ea20dc
c1ccc(-c2ccc3cncnc3c2)nc1
O=[C;H0;D3;+0:1](-[C;D1;H3:2])-[NH;D2;+0:3]-[c:4](:[c:5]):[c:6](-[C;H0;D3;+0:7](-[NH2;D1;+0:8])=[O;H0;D1;+0:9]):[c:10]>>[C;D1;H3:2]-[c;H0;D3;+0:1]1:[n;H0;D2;+0:3]:[c:4](:[c:5]):[c:6](:[c:10]):[c;H0;D3;+0:7](-[OH;D1;+0:9]):[n;H0;D2;+0:8]:1
null
[]
null
null
30
MINUTE
Suspend 2-acetylamino-4-(3-trifluoromethyl-pyridin-2-yl)-benzamide in 20 ml of 20% NaOH, stir for 30 minutes at room temperature. Filter, acidify to pH=6, extract with EtOAc, and concentrate under vacuum to give 2-methyl-7-(3-trifluoromethyl-pyridin-2-yl)-quinazolin-4-ol. Conditions: See reaction.notes.procedure_detail...
10.6084/m9.figshare.5104873.v1
null
Primary amide.Secondary amide
Aromatic alcohol
c1ccccc1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.c1ccncc1
HO-
[OH-].[Na+]
null
0.5
CC(=O)Nc1cc(-c2ncccc2C(F)(F)F)ccc1C(N)=O>[OH-].[Na+]>Cc1nc(O)c2ccc(-c3ncccc3C(F)(F)F)cc2n1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-8c67d5a5246c43f6b27f534f46c29b96
CC(C)(C)c1ccc(N)cc1.Cc1nc(Cl)c2ccc(-c3ncccc3C(F)(F)F)cc2n1>>Cc1nc(Nc2ccc(C(C)(C)C)cc2)c2ccc(-c3ncccc3C(F)(F)F)cc2n1
ClC1=NC(=NC2=CC(=CC=C12)C1=NC=CC=C1C(F)(F)F)C.C(C)(C)(C)C1=CC=C(N)C=C1>>C(C)(C)(C)C1=CC=C(C=C1)NC1=NC(=NC2=CC(=CC=C12)C1=NC=CC=C1C(F)(F)F)C
[NH2:5][c:6]1[cH:7][cH:8][c:9]([C:10]([CH3:11])([CH3:12])[CH3:13])[cH:14][cH:15]1.Cl[c:4]1[n:3][c:2]([CH3:1])[n:32][c:31]2[c:16]1[cH:17][cH:18][c:19](-[c:20]1[n:21][cH:22][cH:23][cH:24][c:25]1[C:26]([F:27])([F:28])[F:29])[cH:30]2>>[CH3:1][c:2]1[n:3][c:4]([NH:5][c:6]2[cH:7][cH:8][c:9]([C:10]([CH3:11])([CH3:12])[CH3:13])...
CC(C)(C)c1ccc(N)cc1.Cc1nc(Cl)c2ccc(-c3ncccc3C(F)(F)F)cc2n1
Cc1nc(Nc2ccc(C(C)(C)C)cc2)c2ccc(-c3ncccc3C(F)(F)F)cc2n1
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(Nc2ncnc3cc(-c4ccccn4)ccc23)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[NH2;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[NH;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
null
[]
null
null
null
null
Using procedures analogous to those already described, (4-tert-Butyl-phenyl)-[2-methyl-7-(3-trifluoromethyl-pyridin-2-yl)-quinazolin-4-yl]-amine is prepared by condensing 4-chloro-2-methyl-7-(3-trifluoromethyl-pyridin-2-yl)-quinazoline with 4-tert-butylaniline. Mass spec. 436.2. Conditions: See reaction.notes.procedure...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccccc1.c1ccc2ncncc2c1.c1ccncc1
HCl
null
null
null
CC(C)(C)c1ccc(N)cc1.Cc1nc(Cl)c2ccc(-c3ncccc3C(F)(F)F)cc2n1>>Cc1nc(Nc2ccc(C(C)(C)C)cc2)c2ccc(-c3ncccc3C(F)(F)F)cc2n1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-ff5bf02e260d4b349a75ea60e675fe3b
Cc1ccc(B(O)O)cc1.FC(F)(F)c1cccnc1Cl>>Cc1ccc(-c2ncccc2C(F)(F)F)cc1
ClC1=NC=CC=C1C(F)(F)F.B(C=1C=CC(=CC1)C)(O)O.C(=O)([O-])[O-].[Na+].[Na+]>>C1(=CC=C(C=C1)C1=NC=CC=C1C(F)(F)F)C
OB(O)[c:5]1[cH:4][cH:3][c:2]([CH3:1])[cH:17][cH:16]1.Cl[c:6]1[n:7][cH:8][cH:9][cH:10][c:11]1[C:12]([F:13])([F:14])[F:15]>>[CH3:1][c:2]1[cH:3][cH:4][c:5](-[c:6]2[n:7][cH:8][cH:9][cH:10][c:11]2[C:12]([F:13])([F:14])[F:15])[cH:16][cH:17]1
Cc1ccc(B(O)O)cc1.FC(F)(F)c1cccnc1Cl
Cc1ccc(-c2ncccc2C(F)(F)F)cc1
null
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1
COCCOC
C-C Coupling
Suzuki coupling with boronic acids
07e9b6e71d806aa92d4573f3838e77c7c8344de3e5d5735ebdb5fc6862ebf27d
08d2969413ef1a2cd5b43667268ba178160c7b55545bf48018e31f2b019632ec
c1ccc(-c2ccccn2)cc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](-[C:5](-[F;D1;H0:6])(-[F;D1;H0:7])-[F;D1;H0:8]):[c:9].O-B(-O)-[c;H0;D3;+0:10](:[c:11]:[c:12]):[c:13]:[c:14]>>[F;D1;H0:6]-[C:5](-[F;D1;H0:7])(-[F;D1;H0:8])-[c:4](:[c:9]):[c;H0;D3;+0:1](-[c;H0;D3;+0:10](:[c:11]:[c:12]):[c:13]:[c:14]):[#7;a:2]:[c:3]
null
[]
80
CELSIUS
8
HOUR
To a de-gassed mixture of 2-chloro-3-(trifluoromethyl)-pyridine (70.1 mmol), p-tolylboronic acid (70.6 mmol), and 2M Na2CO3 (175.0 mmol), in DME (200 mL) under nitrogen add Pd(PPh3)4 (2.8 mmol). Stir the mixture at 80° C. for overnight, concentrate, extract with EtOAc. Dry over Na2SO4, concentrate under vacuum, pass a ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Boronic acid
null
c1ccccc1.c1ccncc1
c1ccccc1.c1ccncc1
c1ccccc1.c1ccncc1
HCl.B
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.COCCOC
80
8
Cc1ccc(B(O)O)cc1.FC(F)(F)c1cccnc1Cl>C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.COCCOC>Cc1ccc(-c2ncccc2C(F)(F)F)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-ebbf801a55804f969f2c1ed3987f9bf7
Cc1ccc(-c2ncccc2C(F)(F)F)cc1.O=[N+]([O-])O>>Cc1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
C1(=CC=C(C=C1)C1=NC=CC=C1C(F)(F)F)C.[N+](=O)(O)[O-]>>CC1=C(C=C(C=C1)C1=NC=CC=C1C(F)(F)F)[N+](=O)[O-]
[CH3:1][c:2]1[cH:3][cH:4][c:5](-[c:6]2[n:7][cH:8][cH:9][cH:10][c:11]2[C:12]([F:13])([F:14])[F:15])[cH:16][cH:17]1.O[N+:18](=[O:19])[O-:20]>>[CH3:1][c:2]1[cH:3][cH:4][c:5](-[c:6]2[n:7][cH:8][cH:9][cH:10][c:11]2[C:12]([F:13])([F:14])[F:15])[cH:16][c:17]1[N+:18](=[O:19])[O-:20]
Cc1ccc(-c2ncccc2C(F)(F)F)cc1.O=[N+]([O-])O
Cc1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
null
null
OS(=O)(=O)O
Functional Group Addition
Aromatic nitration with HNO3
53848b8b2bb4e867226e49db2e60519b24be9379900e3ad7c56af54fe8fde7a5
ddce49825c02b8965f10c8d99e3c841d26e1f136da6037b417c09313e6d73097
c1ccc(-c2ccccn2)cc1
O-[N+;H0;D3:1](-[O;-;D1;H0:2])=[O;D1;H0:3].[C;D1;H3:4]-[c:5](:[c:6]):[cH;D2;+0:7]:[c:8]:[c:9]>>[C;D1;H3:4]-[c:5](:[c:6]):[c;H0;D3;+0:7](-[N+;H0;D3:1](-[O;-;D1;H0:2])=[O;D1;H0:3]):[c:8]:[c:9]
null
[]
null
null
60
MINUTE
To a solution of 2-p-tolyl-3-trifluoromethyl-pyridine (8.4 mmol) in H2SO4 (6 mL) cautiously add fuming HNO3 (2 ml). Stir the mixture 60 minutes at room temperature. Pour the mixture onto ice-water (30 mL), extract with EtOAc, neutralize with 1 N NaOH, dry over Na2SO4, and concentrate under vacuum to obtain 2-(4-methyl-...
10.6084/m9.figshare.5104873.v1
null
Nitrate
Nitro group
c1ccccc1
c1ccccc1
c1ccccc1.c1ccncc1
HO-
OS(=O)(=O)O
null
1
Cc1ccc(-c2ncccc2C(F)(F)F)cc1.O=[N+]([O-])O>OS(=O)(=O)O>Cc1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-5526c94546d94210aab6ec50f967604d
O=C(O)c1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]>>Nc1cc(-c2ncccc2C(F)(F)F)ccc1C(=O)O
[N+](=O)([O-])C1=C(C(=O)O)C=CC(=C1)C1=NC=CC=C1C(F)(F)F>>NC1=C(C(=O)O)C=CC(=C1)C1=NC=CC=C1C(F)(F)F
O=[N+:1]([O-])[c:2]1[cH:3][c:4](-[c:5]2[n:6][cH:7][cH:8][cH:9][c:10]2[C:11]([F:12])([F:13])[F:14])[cH:15][cH:16][c:17]1[C:18](=[O:19])[OH:20]>>[NH2:1][c:2]1[cH:3][c:4](-[c:5]2[n:6][cH:7][cH:8][cH:9][c:10]2[C:11]([F:12])([F:13])[F:14])[cH:15][cH:16][c:17]1[C:18](=[O:19])[OH:20]
O=C(O)c1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
Nc1cc(-c2ncccc2C(F)(F)F)ccc1C(=O)O
null
[Pd]
CCO
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccc(-c2ccccn2)cc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]-[C:5](=[O;D1;H0:6])-[O;D1;H1:7]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]-[C:5](=[O;D1;H0:6])-[O;D1;H1:7]
null
[]
null
null
null
null
Hydrogenate the solution of 2-nitro-4-(3-trifluoromethyl-pyridin-2-yl)-benzoic acid (3.84 mmol) in 95% EtOH (100 mL) with 10% Pd-C (150 mg) for over night. Filter through a celite pad and concentrate the filtrate to give 2-amino-4(3-trifluoromethyl-pyridin-2-yl)-benzoic acid. Conditions: See reaction.notes.procedure_de...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccccc1.c1ccncc1
Other
[Pd].CCO
null
null
O=C(O)c1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]>[Pd].CCO>Nc1cc(-c2ncccc2C(F)(F)F)ccc1C(=O)O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e3adbc372bc5406985e2d7235123dadd
NC=O.Nc1cc(-c2ncccc2C(F)(F)F)ccc1C(=O)O>>Oc1ncnc2cc(-c3ncccc3C(F)(F)F)ccc12
NC1=C(C(=O)O)C=CC(=C1)C1=NC=CC=C1C(F)(F)F.C(=O)N>>FC(C=1C(=NC=CC1)C1=CC=C2C(=NC=NC2=C1)O)(F)F
O=[CH:4][NH2:3].O=[C:2]([OH:1])[c:21]1[c:6]([NH2:5])[cH:7][c:8](-[c:9]2[n:10][cH:11][cH:12][cH:13][c:14]2[C:15]([F:16])([F:17])[F:18])[cH:19][cH:20]1>>[OH:1][c:2]1[n:3][cH:4][n:5][c:6]2[cH:7][c:8](-[c:9]3[n:10][cH:11][cH:12][cH:13][c:14]3[C:15]([F:16])([F:17])[F:18])[cH:19][cH:20][c:21]12
NC=O.Nc1cc(-c2ncccc2C(F)(F)F)ccc1C(=O)O
Oc1ncnc2cc(-c3ncccc3C(F)(F)F)ccc12
null
null
O
Aromatic Heterocycle Formation
OtherReaction
807899eca8aaecfbdeb908b04e93e4879b6b55eeb0c8734b3c80bf4c35c09f84
4f04e8811a54bdec385d5b77090c28cd7db5e4c638bda2b6e8fa910a109c2f98
c1ccc(-c2ccc3cncnc3c2)nc1
O=[C;H0;D3;+0:1](-[O;D1;H1:2])-[c:3](:[c:4]):[c:5](-[NH2;D1;+0:6]):[c:7].O=[CH;D2;+0:8]-[NH2;D1;+0:9]>>[O;D1;H1:2]-[c;H0;D3;+0:1]1:[n;H0;D2;+0:9]:[cH;D2;+0:8]:[n;H0;D2;+0:6]:[c:5](:[c:7]):[c:3]:1:[c:4]
null
[]
null
null
null
null
Stir the mixture of 2-amino-4-(3-trifluoromethyl-pyridin-2-yl)-benzoic acid (1.95 mmol) in HCONH2 (10 mL) for 4 hours at 145° C. Cool to room temperature, dilute with 20 ml of water, and collect the precipitate to give 7-(3-trifluoromethyl-pyridin-2-yl)-quinazolin-4-ol. Conditions: See reaction.notes.procedure_details....
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amide.Primary amine
Aromatic alcohol
c1ccccc1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.c1ccncc1
HO-
O
null
null
NC=O.Nc1cc(-c2ncccc2C(F)(F)F)ccc1C(=O)O>O>Oc1ncnc2cc(-c3ncccc3C(F)(F)F)ccc12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f2e2eccf6d8f41b5a9eb8ad2f9b6aa0c
CC(C)(C)c1ccc([N-]c2ncnc3cc(-c4ncccc4C(F)(F)F)ccc23)cc1>>CC(C)(C)c1ccc(Nc2ncnc3cc(-c4ncccc4C(F)(F)F)ccc23)cc1
Cl.C(C)(C)(C)C1=CC=C(C=C1)[N-]C1=NC=NC2=CC(=CC=C12)C1=NC=CC=C1C(F)(F)F.FC(C=1C(=NC=CC1)C1=CC=C2C(=NC=NC2=C1)O)(F)F>>Cl.C(C)(C)(C)C1=CC=C(C=C1)NC1=NC=NC2=CC(=CC=C12)C1=NC=CC=C1C(F)(F)F
[CH3:1][C:2]([CH3:3])([CH3:4])[c:5]1[cH:6][cH:7][c:8]([N-:9][c:10]2[n:11][cH:12][n:13][c:14]3[cH:15][c:16](-[c:17]4[n:18][cH:19][cH:20][cH:21][c:22]4[C:23]([F:24])([F:25])[F:26])[cH:27][cH:28][c:29]23)[cH:30][cH:31]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[c:5]1[cH:6][cH:7][c:8]([NH:9][c:10]2[n:11][cH:12][n:13][c:14]3[cH:15][c...
CC(C)(C)c1ccc([N-]c2ncnc3cc(-c4ncccc4C(F)(F)F)ccc23)cc1
CC(C)(C)c1ccc(Nc2ncnc3cc(-c4ncccc4C(F)(F)F)ccc23)cc1
null
null
null
Reduction
OtherReaction
5899c0b633c6821428aeb398f81b78a3426e5426f42dc475166a23c6e1174732
2b7f370a519e29b4dede190aa36b37f30822496e32f2c8bfa9736e631bde52e2
c1ccc(Nc2ncnc3cc(-c4ccccn4)ccc23)cc1
[c:1]:[c:2](-[N-;H0;D2:3]-[c:4]1:[#7;a:5]:[c:6]:[#7;a:7]:[c:8]:[c:9]:1):[c:10]>>[c:1]:[c:2](-[NH;D2;+0:3]-[c:4]1:[#7;a:5]:[c:6]:[#7;a:7]:[c:8]:[c:9]:1):[c:10]
null
[]
null
null
null
null
Using procedures analogous to those described above (see, for example, Schemes 1 and 2), (4-tert-Butyl-phenyl)-[7-(3-trifluoromethyl-pyridin-2-yl)-quinazolin-4-yl]-amide hydrochloride is prepared from 7-(3-trifluoromethyl-pyridin-2-yl)-quinazolin-4-ol in two steps. Mass spec. 422.2. Conditions: See reaction.notes.proce...
10.6084/m9.figshare.5104873.v1
null
null
Secondary amine
null
null
c1ccccc1.c1ccc2ncncc2c1.c1ccncc1
null
null
null
null
CC(C)(C)c1ccc([N-]c2ncnc3cc(-c4ncccc4C(F)(F)F)ccc23)cc1>>CC(C)(C)c1ccc(Nc2ncnc3cc(-c4ncccc4C(F)(F)F)ccc23)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-eff5ad7dd6fd44f08cb701595aa21c78
Cc1ccc(B(O)O)cc1.FC(F)(F)c1cccnc1Cl>>Cc1ccc(-c2ncccc2C(F)(F)F)cc1
ClC1=NC=CC=C1C(F)(F)F.B(C=1C=CC(=CC1)C)(O)O.C(=O)([O-])[O-].[Na+].[Na+]>>C1(=CC=C(C=C1)C1=NC=CC=C1C(F)(F)F)C
OB(O)[c:5]1[cH:4][cH:3][c:2]([CH3:1])[cH:17][cH:16]1.Cl[c:6]1[n:7][cH:8][cH:9][cH:10][c:11]1[C:12]([F:13])([F:14])[F:15]>>[CH3:1][c:2]1[cH:3][cH:4][c:5](-[c:6]2[n:7][cH:8][cH:9][cH:10][c:11]2[C:12]([F:13])([F:14])[F:15])[cH:16][cH:17]1
Cc1ccc(B(O)O)cc1.FC(F)(F)c1cccnc1Cl
Cc1ccc(-c2ncccc2C(F)(F)F)cc1
null
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1
COC
C-C Coupling
Suzuki coupling with boronic acids
07e9b6e71d806aa92d4573f3838e77c7c8344de3e5d5735ebdb5fc6862ebf27d
08d2969413ef1a2cd5b43667268ba178160c7b55545bf48018e31f2b019632ec
c1ccc(-c2ccccn2)cc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](-[C:5](-[F;D1;H0:6])(-[F;D1;H0:7])-[F;D1;H0:8]):[c:9].O-B(-O)-[c;H0;D3;+0:10](:[c:11]:[c:12]):[c:13]:[c:14]>>[F;D1;H0:6]-[C:5](-[F;D1;H0:7])(-[F;D1;H0:8])-[c:4](:[c:9]):[c;H0;D3;+0:1](-[c;H0;D3;+0:10](:[c:11]:[c:12]):[c:13]:[c:14]):[#7;a:2]:[c:3]
null
[]
80
CELSIUS
8
HOUR
To a de-gassed mixture of 2-chloro-3-(trifluoromethyl)-pyridine (70.1 mmol), p-tolylboronic acid (70.6 mmol), and 2M Na2CO3 (175.0 mmol), in dimethyl ether (DME; 200 mL) under nitrogen, add Pd(PPh3)4 (2.8 mmol). Stir the mixture at 80° C. overnight, concentrate, and extract with EtOAc. Dry over Na2SO4, concentrate unde...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Boronic acid
null
c1ccccc1.c1ccncc1
c1ccccc1.c1ccncc1
c1ccccc1.c1ccncc1
HCl.B
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.COC
80
8
Cc1ccc(B(O)O)cc1.FC(F)(F)c1cccnc1Cl>C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.COC>Cc1ccc(-c2ncccc2C(F)(F)F)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-61f36f4f067542aeb4b717764343315a
Cc1ccc(-c2ncccc2C(F)(F)F)cc1.O=[N+]([O-])O>>Cc1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
C1(=CC=C(C=C1)C1=NC=CC=C1C(F)(F)F)C.[N+](=O)(O)[O-]>>CC1=C(C=C(C=C1)C1=NC=CC=C1C(F)(F)F)[N+](=O)[O-]
[CH3:1][c:2]1[cH:3][cH:4][c:5](-[c:6]2[n:7][cH:8][cH:9][cH:10][c:11]2[C:12]([F:13])([F:14])[F:15])[cH:16][cH:17]1.O[N+:18](=[O:19])[O-:20]>>[CH3:1][c:2]1[cH:3][cH:4][c:5](-[c:6]2[n:7][cH:8][cH:9][cH:10][c:11]2[C:12]([F:13])([F:14])[F:15])[cH:16][c:17]1[N+:18](=[O:19])[O-:20]
Cc1ccc(-c2ncccc2C(F)(F)F)cc1.O=[N+]([O-])O
Cc1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
null
null
OS(=O)(=O)O
Functional Group Addition
Aromatic nitration with HNO3
53848b8b2bb4e867226e49db2e60519b24be9379900e3ad7c56af54fe8fde7a5
ddce49825c02b8965f10c8d99e3c841d26e1f136da6037b417c09313e6d73097
c1ccc(-c2ccccn2)cc1
O-[N+;H0;D3:1](-[O;-;D1;H0:2])=[O;D1;H0:3].[C;D1;H3:4]-[c:5](:[c:6]):[cH;D2;+0:7]:[c:8]:[c:9]>>[C;D1;H3:4]-[c:5](:[c:6]):[c;H0;D3;+0:7](-[N+;H0;D3:1](-[O;-;D1;H0:2])=[O;D1;H0:3]):[c:8]:[c:9]
null
[]
null
null
60
MINUTE
To a solution of 2-p-tolyl-3-trifluoromethyl-pyridine (8.4 mmol) in H2SO4 (6 mL) cautiously add fuming HNO3 (2 ml). Stir the mixture for 60 minutes at room temperature. Pour the mixture onto ice-water (30 mL), extract with EtOAc, neutralize with 1 N NaOH, dry over Na2SO4, and concentrate under vacuum to obtain 2-(4-met...
10.6084/m9.figshare.5104873.v1
null
Nitrate
Nitro group
c1ccccc1
c1ccccc1
c1ccccc1.c1ccncc1
HO-
OS(=O)(=O)O
null
1
Cc1ccc(-c2ncccc2C(F)(F)F)cc1.O=[N+]([O-])O>OS(=O)(=O)O>Cc1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-25c98ecb65a643498749bfa24400f231
NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]>>NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N
[N+](=O)([O-])C1=C(C(=O)N)C=CC(=C1)C1=NC=CC=C1C(F)(F)F>>NC1=C(C(=O)N)C=CC(=C1)C1=NC=CC=C1C(F)(F)F
O=[N+:20]([O-])[c:19]1[c:4]([C:2]([NH2:1])=[O:3])[cH:5][cH:6][c:7](-[c:8]2[n:9][cH:10][cH:11][cH:12][c:13]2[C:14]([F:15])([F:16])[F:17])[cH:18]1>>[NH2:1][C:2](=[O:3])[c:4]1[cH:5][cH:6][c:7](-[c:8]2[n:9][cH:10][cH:11][cH:12][c:13]2[C:14]([F:15])([F:16])[F:17])[cH:18][c:19]1[NH2:20]
NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N
null
[Pd]
C(C)O
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccc(-c2ccccn2)cc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]-[C:5](-[N;D1;H2:6])=[O;D1;H0:7]>>[N;D1;H2:6]-[C:5](=[O;D1;H0:7])-[c:4]:[c:2](-[NH2;D1;+0:1]):[c:3]
null
[]
null
null
16
HOUR
Hydrogenate 2-nitro-4-(3-trifluoromethyl-pyridin-2-yl)-benzamide (1.0 g, 0.0032 mol) with 50 psi of H2 and 100 mg of 10% Pd/C in ethanol. After 16 hours, filter the mixture through celite and concentrate under reduced pressure to give 2-amino-4-(3-trifluoromethyl-pyridin-2-yl)-benzamide as a solid. Conditions: See reac...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccccc1.c1ccncc1
Other
[Pd].C(C)O
null
16
NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]>[Pd].C(C)O>NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4b3eac05377a4c0c8c5e134d87874074
COC(CCl)(OC)OC.NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N>>O=c1[nH]c(CCl)nc2cc(-c3ncccc3C(F)(F)F)ccc12
NC1=C(C(=O)N)C=CC(=C1)C1=NC=CC=C1C(F)(F)F.ClCC(OC)(OC)OC>>ClCC1=NC2=CC(=CC=C2C(N1)=O)C1=NC=CC=C1C(F)(F)F
CO[C:4](OC)(OC)[CH2:5][Cl:6].[O:1]=[C:2]([NH2:3])[c:23]1[c:8]([NH2:7])[cH:9][c:10](-[c:11]2[n:12][cH:13][cH:14][cH:15][c:16]2[C:17]([F:18])([F:19])[F:20])[cH:21][cH:22]1>>[O:1]=[c:2]1[nH:3][c:4]([CH2:5][Cl:6])[n:7][c:8]2[cH:9][c:10](-[c:11]3[n:12][cH:13][cH:14][cH:15][c:16]3[C:17]([F:18])([F:19])[F:20])[cH:21][cH:22][c...
COC(CCl)(OC)OC.NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N
O=c1[nH]c(CCl)nc2cc(-c3ncccc3C(F)(F)F)ccc12
null
null
null
Aromatic Heterocycle Formation
OtherReaction
292ab66b88620748fa9d06e6e4d9b67ede3a8fd233d74022944407012fccec37
7ad6d407a4f6c8573e2bc724851922f3f76bd08d2e3d3a3ddf0a52cbc9de261c
O=c1[nH]cnc2cc(-c3ccccn3)ccc12
C-O-[C;H0;D4;+0:1](-O-C)(-O-C)-[C:2]-[Cl;D1;H0:3].[NH2;D1;+0:4]-[C;H0;D3;+0:5](=[O;D1;H0:6])-[c:7](:[c:8]):[c:9](-[NH2;D1;+0:10]):[c:11]>>[Cl;D1;H0:3]-[C:2]-[c;H0;D3;+0:1]1:[n;H0;D2;+0:10]:[c:9](:[c:11]):[c:7](:[c:8]):[c;H0;D3;+0:5](=[O;D1;H0:6]):[nH;D2;+0:4]:1
null
[]
null
null
null
null
Heat a solution of 2-amino-4-(3-trifluoromethyl-pyridin-2-yl)-benzamide (100 mg, 0.356 mmol) in 2-chloro-1,1,1-trimethoxyethane (bp 138° C.) at 130° C. for 4 hours. Concentrate the mixture under reduced pressure to give 2-chloromethyl-7-(3-trifluoromethyl-pyridin-2-yl)-3H-quinazolin-4-one as an oil which crystallizes o...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether.Ether.Primary amide.Primary amine
null
c1ccccc1
c1ccc2cncnc2c1
c1ccc2cncnc2c1.c1ccncc1
HO-
null
null
null
COC(CCl)(OC)OC.NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N>>O=c1[nH]c(CCl)nc2cc(-c3ncccc3C(F)(F)F)ccc12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-87c2238b1c034b13987037b2f6511d44
C1CCNC1.FC(F)(F)c1ccc(Nc2nc(CCl)nc3cc(-c4ncccc4C(F)(F)F)ccc23)cc1>>FC(F)(F)c1ccc(Nc2nc(CN3CCCC3)nc3cc(-c4ncccc4C(F)(F)F)ccc23)cc1
Cl.ClCC1=NC2=CC(=CC=C2C(=N1)NC1=CC=C(C=C1)C(F)(F)F)C1=NC=CC=C1C(F)(F)F.N1CCCC1>>N1(CCCC1)CC1=NC2=CC(=CC=C2C(=N1)NC1=CC=C(C=C1)C(F)(F)F)C1=NC=CC=C1C(F)(F)F
[NH:14]1[CH2:15][CH2:16][CH2:17][CH2:18]1.Cl[CH2:13][c:12]1[n:11][c:10]([NH:9][c:8]2[cH:7][cH:6][c:5]([C:2]([F:1])([F:3])[F:4])[cH:37][cH:36]2)[c:35]2[c:20]([n:19]1)[cH:21][c:22](-[c:23]1[n:24][cH:25][cH:26][cH:27][c:28]1[C:29]([F:30])([F:31])[F:32])[cH:33][cH:34]2>>[F:1][C:2]([F:3])([F:4])[c:5]1[cH:6][cH:7][c:8]([NH:9...
C1CCNC1.FC(F)(F)c1ccc(Nc2nc(CCl)nc3cc(-c4ncccc4C(F)(F)F)ccc23)cc1
FC(F)(F)c1ccc(Nc2nc(CN3CCCC3)nc3cc(-c4ncccc4C(F)(F)F)ccc23)cc1
null
null
null
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
19b442dc26882f89f7423416f5e0a16bdb8e48776df57991434a0634e21f0505
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
c1ccc(Nc2nc(CN3CCCC3)nc3cc(-c4ccccn4)ccc23)cc1
Cl-[CH2;D2;+0:1]-[c:2](:[#7;a:3]:[c:4]):[#7;a:5]:[c:6].[C:7]1-[C:8]-[C:9]-[C:10]-[NH;D2;+0:11]-1>>[c:4]:[#7;a:3]:[c:2](-[CH2;D2;+0:1]-[N;H0;D3;+0:11]1-[C:7]-[C:8]-[C:9]-[C:10]-1):[#7;a:5]:[c:6]
null
[]
null
null
null
null
Heat a solution of [2-chloromethyl-7-(3-trifluoromethyl-pyridin-2-yl)-quinazolin-4-yl]-(4-trifluoromethyl-phenyl)-amine HCl (30 mg, 0.058 mmol) in pyrrolidine (1 mL) at 100° C. for 1 hour. Remove the excess pyrrolidine under reduced pressure and partition the residue between EtOAc and 10% NaOH solution. Dry the EtOAc l...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CCNC1
C1CC[NH]C1
c1ccccc1.C1CC[NH]C1.c1ccc2ncncc2c1.c1ccncc1
HCl
null
null
null
C1CCNC1.FC(F)(F)c1ccc(Nc2nc(CCl)nc3cc(-c4ncccc4C(F)(F)F)ccc23)cc1>>FC(F)(F)c1ccc(Nc2nc(CN3CCCC3)nc3cc(-c4ncccc4C(F)(F)F)ccc23)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3838968a21b64ac69cc878ec3d8ac56a
CCOC(=O)c1cnc(-c2ccccc2C(F)(F)F)cc1O.O=P(Cl)(Cl)Cl>>CCOC(=O)c1cnc(-c2ccccc2C(F)(F)F)cc1Cl
C(C)OC(C1=CN=C(C=C1O)C1=C(C=CC=C1)C(F)(F)F)=O.O=P(Cl)(Cl)Cl>>C(C)OC(C1=CN=C(C=C1Cl)C1=C(C=CC=C1)C(F)(F)F)=O
O[c:21]1[c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[cH:7][n:8][c:9](-[c:10]2[cH:11][cH:12][cH:13][cH:14][c:15]2[C:16]([F:17])([F:18])[F:19])[cH:20]1.O=P(Cl)(Cl)[Cl:22]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][n:8][c:9](-[c:10]2[cH:11][cH:12][cH:13][cH:14][c:15]2[C:16]([F:17])([F:18])[F:19])[cH:20][c:21]1[Cl:22]
CCOC(=O)c1cnc(-c2ccccc2C(F)(F)F)cc1O.O=P(Cl)(Cl)Cl
CCOC(=O)c1cnc(-c2ccccc2C(F)(F)F)cc1Cl
null
null
null
Functional Group Interconversion
Alcohol to chloride_POCl3_para
ab85b19a1f19bdb0596b983dc6471067aedf5e7b894e737e6d16cd077bd81b42
e71580a8ffadb7b2717ecd7d68c1d3c0ca161ba5e6a787a49dad5a1359adc993
c1ccc(-c2ccccn2)cc1
Cl-P(-Cl)(=O)-[Cl;H0;D1;+0:1].O-[c;H0;D3;+0:2]1:[c:3]:[c:4](-[c:5]):[#7;a:6]:[c:7]:[c:8]:1-[C:9](=[O;D1;H0:10])-[#8:11]-[C:12]>>[C:12]-[#8:11]-[C:9](=[O;D1;H0:10])-[c:8]1:[c:7]:[#7;a:6]:[c:4](-[c:5]):[c:3]:[c;H0;D3;+0:2]:1-[Cl;H0;D1;+0:1]
null
[]
null
null
null
null
Heat a mixture of 4-Hydroxy-6-(2-trifluoromethyl-phenyl)-nicotinic acid ethyl ester (9.0 g, 0.029 mol) in POCl3 (22 g) at 110° C. for 2 hours. Evaporate the POCl3, and add ice (100 g) followed by careful addition of saturated NaHCO3. Extract with EtOAc, dry (MgSO4), and evaporate to provide 4-chloro-6-(2-trifluoromethy...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol
Aromatic halide
c1ccncc1
c1ccncc1
c1ccncc1.c1ccccc1
HCl
null
null
null
CCOC(=O)c1cnc(-c2ccccc2C(F)(F)F)cc1O.O=P(Cl)(Cl)Cl>>CCOC(=O)c1cnc(-c2ccccc2C(F)(F)F)cc1Cl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-903c4ac65eb141e68dc8be222cbf9a17
CC1CN(Cc2nc(O)c3cnc(-c4ccccc4C(F)(F)F)cc3n2)CC(C)O1.O=P(Cl)(Cl)Cl>>CC1CN(Cc2nc(Cl)c3cnc(-c4ccccc4C(F)(F)F)cc3n2)CC(C)O1
CC1CN(CC(O1)C)CC=1N=C(C2=C(N1)C=C(N=C2)C2=C(C=CC=C2)C(F)(F)F)O.N1=C(C=CC=C1C)C.O=P(Cl)(Cl)Cl>>ClC=1C2=C(N=C(N1)CN1CC(OC(C1)C)C)C=C(N=C2)C2=C(C=CC=C2)C(F)(F)F
O[c:8]1[n:7][c:6]([CH2:5][N:4]2[CH2:3][CH:2]([CH3:1])[O:30][CH:28]([CH3:29])[CH2:27]2)[n:26][c:25]2[c:10]1[cH:11][n:12][c:13](-[c:14]1[cH:15][cH:16][cH:17][cH:18][c:19]1[C:20]([F:21])([F:22])[F:23])[cH:24]2.O=P(Cl)(Cl)[Cl:9]>>[CH3:1][CH:2]1[CH2:3][N:4]([CH2:5][c:6]2[n:7][c:8]([Cl:9])[c:10]3[cH:11][n:12][c:13](-[c:14]4[...
CC1CN(Cc2nc(O)c3cnc(-c4ccccc4C(F)(F)F)cc3n2)CC(C)O1.O=P(Cl)(Cl)Cl
CC1CN(Cc2nc(Cl)c3cnc(-c4ccccc4C(F)(F)F)cc3n2)CC(C)O1
null
null
C(Cl)(Cl)Cl
Functional Group Interconversion
Alcohol to chloride_POCl3_ortho
aadd06203830e902e59b15792f3dac5d156894dc4789a75d727b008defc19073
e71580a8ffadb7b2717ecd7d68c1d3c0ca161ba5e6a787a49dad5a1359adc993
c1ccc(-c2cc3nc(CN4CCOCC4)ncc3cn2)cc1
Cl-P(-Cl)(=O)-[Cl;H0;D1;+0:1].O-[c;H0;D3;+0:2]1:[#7;a:3]:[c:4]:[#7;a:5]:[c:6]2:[c:7]:[c:8]:[#7;a:9]:[c:10]:[c:11]:2:1>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[#7;a:3]:[c:4]:[#7;a:5]:[c:6]2:[c:7]:[c:8]:[#7;a:9]:[c:10]:[c:11]:2:1
null
[]
null
null
null
null
Reflux a mixture of 2-(2,6-dimethyl-morpholin-4-ylmethyl)-7-(2-trifluoromethyl-phenyl)-pyrido[4,3-d]-pyrimidin-4-ol (0.6 g), 2,6-lutidine (0.62 g), and POCl3 (1.1 g) in CHCl3 (15 mL) for 20 hours. Cool the mixture and concentrate under reduced pressure. Partition the residue between EtOAc and saturated NaHCO3 solution....
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol
Aromatic halide
c1cc2ncncc2cn1
c1cc2ncncc2cn1
C1COCC[NH]1.c1cc2ncncc2cn1.c1ccccc1
HCl
C(Cl)(Cl)Cl
null
null
CC1CN(Cc2nc(O)c3cnc(-c4ccccc4C(F)(F)F)cc3n2)CC(C)O1.O=P(Cl)(Cl)Cl>C(Cl)(Cl)Cl>CC1CN(Cc2nc(Cl)c3cnc(-c4ccccc4C(F)(F)F)cc3n2)CC(C)O1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-9cff6c91ca054fd6816673ec0f99cc15
COc1ccc(B(O)O)cn1.FC(F)(F)c1cccnc1Cl>>COc1ccc(-c2ncccc2C(F)(F)F)cn1
ClC1=NC=CC=C1C(F)(F)F.COC1=NC=C(C=C1)B(O)O.C([O-])([O-])=O.[K+].[K+]>>COC1=CC=C(C=N1)C1=NC=CC=C1C(F)(F)F
OB(O)[c:6]1[cH:5][cH:4][c:3]([O:2][CH3:1])[n:18][cH:17]1.Cl[c:7]1[n:8][cH:9][cH:10][cH:11][c:12]1[C:13]([F:14])([F:15])[F:16]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6](-[c:7]2[n:8][cH:9][cH:10][cH:11][c:12]2[C:13]([F:14])([F:15])[F:16])[cH:17][n:18]1
COc1ccc(B(O)O)cn1.FC(F)(F)c1cccnc1Cl
COc1ccc(-c2ncccc2C(F)(F)F)cn1
null
[Pd].C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1
C1(=CC=CC=C1)C
C-C Coupling
Suzuki coupling with boronic acids
2e12f1697d123c35af029842984dda76c08cdd06401f05924c6b1363bf342af9
08d2969413ef1a2cd5b43667268ba178160c7b55545bf48018e31f2b019632ec
c1ccc(-c2cccnc2)nc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](-[C:5](-[F;D1;H0:6])(-[F;D1;H0:7])-[F;D1;H0:8]):[c:9].O-B(-O)-[c;H0;D3;+0:10]1:[c:11]:[#7;a:12]:[c:13]:[c:14]:[c:15]:1>>[F;D1;H0:6]-[C:5](-[F;D1;H0:7])(-[F;D1;H0:8])-[c:4](:[c:9]):[c;H0;D3;+0:1](-[c;H0;D3;+0:10]1:[c:11]:[#7;a:12]:[c:13]:[c:14]:[c:15]:1):[#7;a:2]:[c:3]
95
[{"value": 95.0, "product": "COC1=CC=C(C=N1)C1=NC=CC=C1C(F)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 94.8, "product": "COC1=CC=C(C=N1)C1=NC=CC=C1C(F)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
Heat a mixture of 2-chloro-3-trifluoromethylpyridine (37 g, 0.2 mol), 2-methoxypyridine-5-boronic acid (32 g, 0.21 mol), tetrakis(triphenylphosphine) palladium(0) (9 g, 7 mmol) and 2M potassium carbonate (150 mL) in toluene (500 mL) under a nitrogen atmosphere, at 90° C. for 8 hours. Cool the reaction mixture and separ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Boronic acid
null
c1ccncc1.c1ccncc1
c1ccncc1.c1ccncc1
c1ccncc1.c1ccncc1
HCl.B
[Pd].C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)C
null
8
COc1ccc(B(O)O)cn1.FC(F)(F)c1cccnc1Cl>[Pd].C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)C>COc1ccc(-c2ncccc2C(F)(F)F)cn1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d6e6a6a37c1d44189bc651ece3388da5
COc1ccc(-c2ncccc2C(F)(F)F)cn1>>O=c1ccc(-c2ncccc2C(F)(F)F)c[nH]1
COC1=CC=C(C=N1)C1=NC=CC=C1C(F)(F)F>>FC(C=1C(=NC=CC1)C1=CNC(C=C1)=O)(F)F
C[O:1][c:2]1[cH:3][cH:4][c:5](-[c:6]2[n:7][cH:8][cH:9][cH:10][c:11]2[C:12]([F:13])([F:14])[F:15])[cH:16][n:17]1>>[O:1]=[c:2]1[cH:3][cH:4][c:5](-[c:6]2[n:7][cH:8][cH:9][cH:10][c:11]2[C:12]([F:13])([F:14])[F:15])[cH:16][nH:17]1
COc1ccc(-c2ncccc2C(F)(F)F)cn1
O=c1ccc(-c2ncccc2C(F)(F)F)c[nH]1
null
null
Br.CC(=O)O
Miscellaneous
OtherReaction
ffbb4288e7102e6f227d930be4a9510dc9e13ff3142954fd43347db64909ca58
291cad8b6dfbbd2c823b5c9d45efc37a166dc3454a9f151ac48cb357f4bc155f
O=c1ccc(-c2ccccn2)c[nH]1
C-[O;H0;D2;+0:1]-[c;H0;D3;+0:2]1:[c:3]:[c:4]:[c:5]:[c:6]:[n;H0;D2;+0:7]:1>>[O;H0;D1;+0:1]=[c;H0;D3;+0:2]1:[c:3]:[c:4]:[c:5]:[c:6]:[nH;D2;+0:7]:1
93.7
[{"value": 93.0, "product": "FC(C=1C(=NC=CC1)C1=CNC(C=C1)=O)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 93.7, "product": "FC(C=1C(=NC=CC1)C1=CNC(C=C1)=O)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
Heat 6′-methoxy-3-trifluoromethyl-[2,3′]bipyridinyl (41 g, 0.16 mol) in 30% HBr/AcOH (100 mL) to reflux for 1 hour. Cool the mixture and filter, and wash the precipitate with ether (100 mL). Transfer the precipitate into 10M sodium hydroxide (500 mL) and stir for 1 hour, and treat the solution with hydrochloric acid un...
10.6084/m9.figshare.5104873.v1
null
Ether
null
c1ccncc1
c1cccnc1
c1cccnc1.c1ccncc1
Other
Br.CC(=O)O
null
1
COc1ccc(-c2ncccc2C(F)(F)F)cn1>Br.CC(=O)O>O=c1ccc(-c2ncccc2C(F)(F)F)c[nH]1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c9d0b11af3a8457186a777d347054dd5
O=[N+]([O-])O.O=c1ccc(-c2ncccc2C(F)(F)F)c[nH]1>>O=c1[nH]cc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
FC(C=1C(=NC=CC1)C1=CNC(C=C1)=O)(F)F.[N+](=O)(O)[O-]>>[N+](=O)([O-])C1=CC(=CNC1=O)C1=NC=CC=C1C(F)(F)F
O[N+:18](=[O:19])[O-:20].[O:1]=[c:2]1[nH:3][cH:4][c:5](-[c:6]2[n:7][cH:8][cH:9][cH:10][c:11]2[C:12]([F:13])([F:14])[F:15])[cH:16][cH:17]1>>[O:1]=[c:2]1[nH:3][cH:4][c:5](-[c:6]2[n:7][cH:8][cH:9][cH:10][c:11]2[C:12]([F:13])([F:14])[F:15])[cH:16][c:17]1[N+:18](=[O:19])[O-:20]
O=[N+]([O-])O.O=c1ccc(-c2ncccc2C(F)(F)F)c[nH]1
O=c1[nH]cc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
null
null
S(O)(O)(=O)=O
Functional Group Addition
Aromatic nitration with HNO3
26a878e97e02b420c859859d3c94a295b28ee7e9c7a3a499b0358675c34410cd
ddce49825c02b8965f10c8d99e3c841d26e1f136da6037b417c09313e6d73097
O=c1ccc(-c2ccccn2)c[nH]1
O-[N+;H0;D3:1](-[O;-;D1;H0:2])=[O;D1;H0:3].[O;D1;H0:4]=[c:5]1:[#7;a:6]:[c:7]:[c:8]:[c:9]:[cH;D2;+0:10]:1>>[O;-;D1;H0:2]-[N+;H0;D3:1](=[O;D1;H0:3])-[c;H0;D3;+0:10]1:[c:9]:[c:8]:[c:7]:[#7;a:6]:[c:5]:1=[O;D1;H0:4]
92
[{"value": 92.0, "product": "[N+](=O)([O-])C1=CC(=CNC1=O)C1=NC=CC=C1C(F)(F)F", "details": "PERCENTYIELD", "is_desired": false}]
70
CELSIUS
null
null
To a solution of 3-trifluoromethyl-1′H-[2,3′]bipyridinyl-6′-one (25 g, 0.1 mol) in concentrated sulfuric acid (100 mL) at 0° C., add dropwise a solution of fuming nitric acid (35 mL) and concentrated sulfuric acid (10 mL). Heat the reaction mixture to 70° C. for 1 hour, cool and pour onto ice (500 mL). Filter the mixtu...
10.6084/m9.figshare.5104873.v1
null
Nitrate
Nitro group
c1cccnc1
c1cnccc1
c1cnccc1.c1ccncc1
HO-
S(O)(O)(=O)=O
70
null
O=[N+]([O-])O.O=c1ccc(-c2ncccc2C(F)(F)F)c[nH]1>S(O)(O)(=O)=O>O=c1[nH]cc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-633bc18231fa495e998db535d27a7700
O=S(Cl)Cl.O=c1[nH]cc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]>>O=[N+]([O-])c1cc(-c2ncccc2C(F)(F)F)cnc1Cl
[N+](=O)([O-])C1=CC(=CNC1=O)C1=NC=CC=C1C(F)(F)F.S(=O)(Cl)Cl>>ClC1=C(C=C(C=N1)C1=NC=CC=C1C(F)(F)F)[N+](=O)[O-]
O=S(Cl)[Cl:20].O=[c:19]1[c:4]([N+:2](=[O:1])[O-:3])[cH:5][c:6](-[c:7]2[n:8][cH:9][cH:10][cH:11][c:12]2[C:13]([F:14])([F:15])[F:16])[cH:17][nH:18]1>>[O:1]=[N+:2]([O-:3])[c:4]1[cH:5][c:6](-[c:7]2[n:8][cH:9][cH:10][cH:11][c:12]2[C:13]([F:14])([F:15])[F:16])[cH:17][n:18][c:19]1[Cl:20]
O=S(Cl)Cl.O=c1[nH]cc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
O=[N+]([O-])c1cc(-c2ncccc2C(F)(F)F)cnc1Cl
null
null
CN(C)C=O
Functional Group Interconversion
OtherReaction
ad993f9ce2ce60b71a2afb3182d5e182b0d0de1be8200a3f161e73174c9a6ebf
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccc(-c2cccnc2)nc1
Cl-S(=O)-[Cl;H0;D1;+0:1].O=[c;H0;D3;+0:2]1:[nH;D2;+0:3]:[c:4]:[c:5]:[c:6]:[c:7]:1-[#7;+:8]>>[#7;+:8]-[c:7]1:[c:6]:[c:5]:[c:4]:[n;H0;D2;+0:3]:[c;H0;D3;+0:2]:1-[Cl;H0;D1;+0:1]
93
[{"value": 93.0, "product": "ClC1=C(C=C(C=N1)C1=NC=CC=C1C(F)(F)F)[N+](=O)[O-]", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Heat a solution of 5′-nitro-3-trifluoromethyl-1′H[2,3′]bipyridinyl-6′-one (25 g, 0.088 mol), thionyl chloride (300 mL) and DMF (3 mL) to reflux for 4 hours. Remove the volatiles by rotary evaporation and partition the residue between ethyl acetate (350 mL) and saturated sodium bicarbonate solution (250 mL). Extract the...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1cnccc1
c1ccncc1
c1ccncc1.c1ccncc1
HCl
CN(C)C=O
null
null
O=S(Cl)Cl.O=c1[nH]cc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]>CN(C)C=O>O=[N+]([O-])c1cc(-c2ncccc2C(F)(F)F)cnc1Cl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b1a11252fbf44ab2a075573749a25439
O=[N+]([O-])c1cc(-c2ncccc2C(F)(F)F)cnc1Cl>>Nc1cc(-c2ncccc2C(F)(F)F)cnc1Cl
ClC1=C(C=C(C=N1)C1=NC=CC=C1C(F)(F)F)[N+](=O)[O-].[Cl-].[Ca+2].[Cl-]>>ClC1=C(C=C(C=N1)C1=NC=CC=C1C(F)(F)F)N
O=[N+:1]([O-])[c:2]1[cH:3][c:4](-[c:5]2[n:6][cH:7][cH:8][cH:9][c:10]2[C:11]([F:12])([F:13])[F:14])[cH:15][n:16][c:17]1[Cl:18]>>[NH2:1][c:2]1[cH:3][c:4](-[c:5]2[n:6][cH:7][cH:8][cH:9][c:10]2[C:11]([F:12])([F:13])[F:14])[cH:15][n:16][c:17]1[Cl:18]
O=[N+]([O-])c1cc(-c2ncccc2C(F)(F)F)cnc1Cl
Nc1cc(-c2ncccc2C(F)(F)F)cnc1Cl
null
[Fe]
O.C(C)O
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccc(-c2cccnc2)nc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4](-[Cl;D1;H0:5]):[#7;a:6]:[c:7]>>[Cl;D1;H0:5]-[c:4](:[#7;a:6]:[c:7]):[c:2](-[NH2;D1;+0:1]):[c:3]
85
[{"value": 85.0, "product": "ClC1=C(C=C(C=N1)C1=NC=CC=C1C(F)(F)F)N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 84.7, "product": "ClC1=C(C=C(C=N1)C1=NC=CC=C1C(F)(F)F)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of 6′-chloro-5′-nitro-3-trifluoromethyl-[2,3′]bipyridinyl (25 g, 0.082 mol) and calcium chloride (11 g, 0.1 mol) in ethanol (300 mL) and water (50 mL), add iron powder (45 g, 0.82 mol). Heat the solution to reflux for 1.5 hours, cool and filter through Celite. Concentrate the mixture under reduced pressur...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccncc1.c1ccncc1
Other
[Fe].O.C(C)O
null
null
O=[N+]([O-])c1cc(-c2ncccc2C(F)(F)F)cnc1Cl>[Fe].O.C(C)O>Nc1cc(-c2ncccc2C(F)(F)F)cnc1Cl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c6601c51f2bb4dacac86f554f419c803
CN(C)C=O.Nc1cc(-c2ncccc2C(F)(F)F)cnc1Cl.[NH4+]>>NC(=O)c1ncc(-c2ncccc2C(F)(F)F)cc1N
CN(C)C=O.[Cl-].[NH4+].[OH-].[NH4+].ClC1=C(C=C(C=N1)C1=NC=CC=C1C(F)(F)F)N>>NC=1C(=NC=C(C1)C1=NC=CC=C1C(F)(F)F)C(=O)N
CN(C)[CH:2]=[O:3].Cl[c:4]1[n:5][cH:6][c:7](-[c:8]2[n:9][cH:10][cH:11][cH:12][c:13]2[C:14]([F:15])([F:16])[F:17])[cH:18][c:19]1[NH2:20].[NH4+:1]>>[NH2:1][C:2](=[O:3])[c:4]1[n:5][cH:6][c:7](-[c:8]2[n:9][cH:10][cH:11][cH:12][c:13]2[C:14]([F:15])([F:16])[F:17])[cH:18][c:19]1[NH2:20]
CN(C)C=O.Nc1cc(-c2ncccc2C(F)(F)F)cnc1Cl.[NH4+]
NC(=O)c1ncc(-c2ncccc2C(F)(F)F)cc1N
null
C1(=CC=CC=C1)P([C-]1C=CC=C1)C1=CC=CC=C1.[C-]1(C=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Fe+2].C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd].C1(=CC=CC=C1)P([C-]1C=CC=C1)C1=CC=CC=C1.[C-]1(C=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Fe+2].[C-]#N.[Zn+2].[C...
O
Acylation
OtherReaction
e1863fb77b18a4f8a4f6f62e441a7222b67756c377f9188d3bd53f6c3965f65f
e877213e19171755e0934a74438f863139f6bd24cdbe9c4b94ecbf55b1179c4e
c1ccc(-c2cccnc2)nc1
C-N(-C)-[CH;D2;+0:1]=[O;D1;H0:2].Cl-[c;H0;D3;+0:3](:[#7;a:4]:[c:5]):[c:6](-[N;D1;H2:7]):[c:8].[NH4+;D0:9]>>[N;D1;H2:7]-[c:6](:[c:8]):[c;H0;D3;+0:3](-[C;H0;D3;+0:1](-[NH2;D1;+0:9])=[O;D1;H0:2]):[#7;a:4]:[c:5]
90
[{"value": 90.0, "product": "NC=1C(=NC=C(C1)C1=NC=CC=C1C(F)(F)F)C(=O)N", "details": "PERCENTYIELD", "is_desired": false}]
0
CELSIUS
1
HOUR
Heat a solution of 6′-chloro-3-trifluoromethyl-[2,3′]bipyridinyl-5′-ylamine (25 g, 0.091 mol), zinc cyanide (6.75 g, 0.058 mol), tris[dibenzylidineacetone]di-palladium (also referred to as “pd2(dba)3”; 2.63 g, 2.86 mmol), 1,1′-bis(diphenylphosphino)ferrocene (also referred to as “DPPF”; 3.16 g, 5.72 mmol) in DMF (250 m...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Tertiary amide
Primary amide
c1ccncc1
c1ccncc1
c1ccncc1.c1ccncc1
HCl
C1(=CC=CC=C1)P([C-]1C=CC=C1)C1=CC=CC=C1.[C-]1(C=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Fe+2].C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd].C1(=CC=CC=C1)P([C-]1C=CC=C1)C1=CC=CC=C1.[C-]1(C=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Fe+2].[C-]#N.[Zn+2].[C...
0
1
CN(C)C=O.Nc1cc(-c2ncccc2C(F)(F)F)cnc1Cl.[NH4+]>C1(=CC=CC=C1)P([C-]1C=CC=C1)C1=CC=CC=C1.[C-]1(C=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Fe+2].C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd].C1(=CC=CC=C1)P([C-]1C=CC=C1)C1=CC=CC=C1.[C-]1(C=CC=C1)P(...
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a766d9f6940a49f19eb8ff062f5be56a
CCOC(=O)CCBr.OCc1ccccc1>>O=C(O)CCOCc1ccccc1
O.[H-].[Na+].C(C1=CC=CC=C1)O.BrCCC(=O)OCC>>C(C1=CC=CC=C1)OCCC(=O)O
CC[O:3][C:2](=[O:1])[CH2:4][CH2:5]Br.[OH:6][CH2:7][c:8]1[cH:9][cH:10][cH:11][cH:12][cH:13]1>>[O:1]=[C:2]([OH:3])[CH2:4][CH2:5][O:6][CH2:7][c:8]1[cH:9][cH:10][cH:11][cH:12][cH:13]1
CCOC(=O)CCBr.OCc1ccccc1
O=C(O)CCOCc1ccccc1
null
null
[OH-].[Na+].C1(=CC=CC=C1)C.CO.C(C)(=O)OCC
Heteroatom Alkylation and Arylation
OtherReaction
649e704edbb364f9da7d07cbe4234c4a92fb1da39cfc9c27b4b5f45f135ea332
618df49e449d2d4d71a5c69761039aa60d2846715c5b4fde87b9028fc160ed45
c1ccccc1
Br-[CH2;D2;+0:1]-[C:2]-[C:3](=[O;D1;H0:4])-[O;H0;D2;+0:5]-C-C.[OH;D1;+0:6]-[C:7]-[c:8]>>[O;D1;H0:4]=[C:3](-[OH;D1;+0:5])-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:6]-[C:7]-[c:8]
34.2
[{"value": 34.0, "product": "C(C1=CC=CC=C1)OCCC(=O)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 34.2, "product": "C(C1=CC=CC=C1)OCCC(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
In small portions, add sodium hydride (2.22 g, 60% dispersion in mineral oil, 55.4 mmol) to a cold (0° C.) solution of benzyl alcohol (4.0 g, 37 mmol) in toluene (100 mL). Add ethyl 3-bromopropionate (8.0 g, 44 mmol) dropwise to the mixture, allow the resulting solution to warm to room temperature and stir for 1 hour. ...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Primary alcohol
Carboxylic acid.Ether
null
null
c1ccccc1
HBr
[OH-].[Na+].C1(=CC=CC=C1)C.CO.C(C)(=O)OCC
null
1
CCOC(=O)CCBr.OCc1ccccc1>[OH-].[Na+].C1(=CC=CC=C1)C.CO.C(C)(=O)OCC>O=C(O)CCOCc1ccccc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-9cb24f038e524d4db0b88314e757605e
CCOC(=O)CCC(=O)Cl.NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N>>CCOC(=O)CCc1nc(O)c2ccc(-c3ncccc3C(F)(F)F)cc2n1
NC1=C(C(=O)N)C=CC(=C1)C1=NC=CC=C1C(F)(F)F.N1=CC=CC=C1.[Cl-].C(C)OC(CCC(=O)Cl)=O.CC[O-].[Na+]>>C(C)OC(CCC1=NC2=CC(=CC=C2C(=N1)O)C1=NC=CC=C1C(F)(F)F)=O
O=[C:8](Cl)[CH2:7][CH2:6][C:4]([O:3][CH2:2][CH3:1])=[O:5].[NH2:9][C:10](=[O:11])[c:12]1[cH:13][cH:14][c:15](-[c:16]2[n:17][cH:18][cH:19][cH:20][c:21]2[C:22]([F:23])([F:24])[F:25])[cH:26][c:27]1[NH2:28]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][CH2:7][c:8]1[n:9][c:10]([OH:11])[c:12]2[cH:13][cH:14][c:15](-[c:16]3[n:17][cH...
CCOC(=O)CCC(=O)Cl.NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N
CCOC(=O)CCc1nc(O)c2ccc(-c3ncccc3C(F)(F)F)cc2n1
null
null
CCO.C1CCOC1
Aromatic Heterocycle Formation
OtherReaction
421874b4cd55eaa20f24b1cd7ba94b5870b5c4e9b00f756449eff425c4e3a153
d5ef1961d36ab2d05e773eb9e606a89406d1ee5463b381ad4c7037e46428ccb9
c1ccc(-c2ccc3cncnc3c2)nc1
Cl-[C;H0;D3;+0:1](=O)-[C:2]-[C:3]-[C:4](-[#8:5])=[O;D1;H0:6].[NH2;D1;+0:7]-[c:8](:[c:9]):[c:10](-[C;H0;D3;+0:11](-[NH2;D1;+0:12])=[O;H0;D1;+0:13]):[c:14]>>[#8:5]-[C:4](=[O;D1;H0:6])-[C:3]-[C:2]-[c;H0;D3;+0:1]1:[n;H0;D2;+0:7]:[c:8](:[c:9]):[c:10](:[c:14]):[c;H0;D3;+0:11](-[OH;D1;+0:13]):[n;H0;D2;+0:12]:1
null
[]
null
null
20
MINUTE
To a solution of 2-amino-4-(3-trifluoromethyl-pyridin-2-yl)-benzamide (0.5 mmol) and pyridine (0.55 mmol) in THF (5 ml), add 3-chlorocarbonyl-propionic acid ethyl ester chloride (0.55 mmol). Stir the mixture for 20 minutes at room temperature, add 20 ml of 21% NaOEt in EtOH, and stir for 30 minutes at 50° C. Concentrat...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amide.Primary amine
Aromatic alcohol
c1ccccc1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.c1ccncc1
HCl
CCO.C1CCOC1
null
0.333333
CCOC(=O)CCC(=O)Cl.NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N>CCO.C1CCOC1>CCOC(=O)CCc1nc(O)c2ccc(-c3ncccc3C(F)(F)F)cc2n1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-bb4891bb14ab4be5a0f03b575865206f
COC(CCl)(OC)OC.NC(=O)c1ccc(Br)cc1N>>O=c1[nH]c(CCl)nc2cc(Br)ccc12
NC1=C(C(=O)N)C=CC(=C1)Br.ClCC(OC)(OC)OC>>BrC1=CC=C2C(NC(=NC2=C1)CCl)=O
CO[C:4](OC)(OC)[CH2:5][Cl:6].[O:1]=[C:2]([NH2:3])[c:14]1[c:8]([NH2:7])[cH:9][c:10]([Br:11])[cH:12][cH:13]1>>[O:1]=[c:2]1[nH:3][c:4]([CH2:5][Cl:6])[n:7][c:8]2[cH:9][c:10]([Br:11])[cH:12][cH:13][c:14]12
COC(CCl)(OC)OC.NC(=O)c1ccc(Br)cc1N
O=c1[nH]c(CCl)nc2cc(Br)ccc12
null
null
null
Aromatic Heterocycle Formation
OtherReaction
292ab66b88620748fa9d06e6e4d9b67ede3a8fd233d74022944407012fccec37
7ad6d407a4f6c8573e2bc724851922f3f76bd08d2e3d3a3ddf0a52cbc9de261c
O=c1[nH]cnc2ccccc12
C-O-[C;H0;D4;+0:1](-O-C)(-O-C)-[C:2]-[Cl;D1;H0:3].[NH2;D1;+0:4]-[C;H0;D3;+0:5](=[O;D1;H0:6])-[c:7](:[c:8]):[c:9](-[NH2;D1;+0:10]):[c:11]>>[Cl;D1;H0:3]-[C:2]-[c;H0;D3;+0:1]1:[n;H0;D2;+0:10]:[c:9](:[c:11]):[c:7](:[c:8]):[c;H0;D3;+0:5](=[O;D1;H0:6]):[nH;D2;+0:4]:1
null
[]
null
null
null
null
Reflux a solution of 2-amino-4-bromobenzamide (27 g, 0.13 mol; see Joshi and Chaudhari, (1987) Indian J. Chem., Sect. B, 26B(6):602-4) in 2-chloro-1,1,1-trimethoxyethane (50 mL) for 30 minutes, during which time a large precipitate appears. Evaporate the mixture fully and triturate with ether to collect 28 g of 7-bromo...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether.Ether.Primary amide.Primary amine
null
c1ccccc1
c1ccc2cncnc2c1
c1ccc2cncnc2c1
HO-
null
null
null
COC(CCl)(OC)OC.NC(=O)c1ccc(Br)cc1N>>O=c1[nH]c(CCl)nc2cc(Br)ccc12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d14c368a73f7413183370a1f21e7e743
O=P(Cl)(Cl)Cl.O=c1[nH]c(CCl)nc2cc(Br)ccc12>>ClCc1nc(Cl)c2ccc(Br)cc2n1
BrC1=CC=C2C(NC(=NC2=C1)CCl)=O.N1=C(C=CC=C1C)C.P(=O)(Cl)(Cl)Cl>>BrC1=CC=C2C(=NC(=NC2=C1)CCl)Cl
O=P(Cl)(Cl)[Cl:6].O=[c:5]1[nH:4][c:3]([CH2:2][Cl:1])[n:14][c:13]2[c:7]1[cH:8][cH:9][c:10]([Br:11])[cH:12]2>>[Cl:1][CH2:2][c:3]1[n:4][c:5]([Cl:6])[c:7]2[cH:8][cH:9][c:10]([Br:11])[cH:12][c:13]2[n:14]1
O=P(Cl)(Cl)Cl.O=c1[nH]c(CCl)nc2cc(Br)ccc12
ClCc1nc(Cl)c2ccc(Br)cc2n1
null
null
COCCOC
Functional Group Interconversion
OtherReaction
5d38f97f3712b237e9f3fba95a694ccb97b6e400bb6127459a74d91e2bc1ab18
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccc2ncncc2c1
Cl-P(-Cl)(=O)-[Cl;H0;D1;+0:1].O=[c;H0;D3;+0:2]1:[nH;D2;+0:3]:[c:4](-[C:5]):[#7;a:6]:[c:7](:[c:8]):[c:9]:1:[c:10]>>[C:5]-[c:4]1:[#7;a:6]:[c:7](:[c:8]):[c:9](:[c:10]):[c;H0;D3;+0:2](-[Cl;H0;D1;+0:1]):[n;H0;D2;+0:3]:1
null
[]
null
null
null
null
Heat a mixture of 7-bromo-2-chloromethyl-3H-quinazolin-4-one (5 g, 18.2 mmol), 2,6-lutidine (5 g), and phosphorus oxychloride (5 mL) in 1,2-dimethoxyethane (500 mL) at 80° C. for 16 hours. Cool the mixture to room temperature and fully evaporate the mixture, then dilute with ether and wash with water. Dry the solvent (...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccc2cncnc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1
HCl
COCCOC
null
null
O=P(Cl)(Cl)Cl.O=c1[nH]c(CCl)nc2cc(Br)ccc12>COCCOC>ClCc1nc(Cl)c2ccc(Br)cc2n1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a6b5fb3780714f14b948c387c47db230
CC#N.Nc1ncc(Br)cc1[N+](=O)[O-]>>N#Cc1ncc(Br)cc1[N+](=O)[O-]
NC1=NC=C(C=C1[N+](=O)[O-])Br.C(C)(C)(C)ON=O.C(C)#N>>BrC=1C=C(C(=NC1)C#N)[N+](=O)[O-]
C[C:2]#[N:1].N[c:3]1[n:4][cH:5][c:6]([Br:7])[cH:8][c:9]1[N+:10](=[O:11])[O-:12]>>[N:1]#[C:2][c:3]1[n:4][cH:5][c:6]([Br:7])[cH:8][c:9]1[N+:10](=[O:11])[O-:12]
CC#N.Nc1ncc(Br)cc1[N+](=O)[O-]
N#Cc1ncc(Br)cc1[N+](=O)[O-]
null
null
null
C-C Coupling
OtherReaction
7be32428aabd580dfbed2e434f7904a98f0e54bc30b8b5f4dba0a6d14252e209
5270ba81df65d040f7a2858a28254c13e4f1fb0313393de6d45aa339bf5619bd
c1ccncc1
C-[C;H0;D2;+0:1]#[N;D1;H0:2].N-[c;H0;D3;+0:3](:[#7;a:4]:[c:5]):[c:6](-[#7;+:7]):[c:8]>>[#7;+:7]-[c:6](:[c:8]):[c;H0;D3;+0:3](-[C;H0;D2;+0:1]#[N;D1;H0:2]):[#7;a:4]:[c:5]
41
[{"value": 41.0, "product": "BrC=1C=C(C(=NC1)C#N)[N+](=O)[O-]", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Heat a solution of 2-amino-5-bromo-3-nitropyridine (2.18 g, 10 mmol), cuprous cyanide (1.33 g, 15 mmol) and tert-butylnitrite (2.0 mL, 15 mmol) in acetonitrile (50 mL) to 60° C. for 2 hours. Cool the solution and partition between ethyl acetate (100 mL) and saturated aqueous NaHCO3 (100 mL). Extract the aqueous solutio...
10.6084/m9.figshare.5104873.v1
null
Nitrile.Primary amine
Nitrile
c1ccncc1
c1ccncc1
c1ccncc1
Other
null
null
null
CC#N.Nc1ncc(Br)cc1[N+](=O)[O-]>>N#Cc1ncc(Br)cc1[N+](=O)[O-]
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-00d87abac6bf41acb621916e25883907
Cc1cccn[c]1[Zn+].N#Cc1ncc(Br)cc1[N+](=O)[O-]>>Cc1cccnc1-c1cnc(C#N)c([N+](=O)[O-])c1
BrC=1C=C(C(=NC1)C#N)[N+](=O)[O-].[Br-].CC=1C(=NC=CC1)[Zn+]>>CC=1C(=NC=CC1)C=1C=C(C(=NC1)C#N)[N+](=O)[O-]
[Zn+][c:7]1[c:2]([CH3:1])[cH:3][cH:4][cH:5][n:6]1.Br[c:8]1[cH:9][n:10][c:11]([C:12]#[N:13])[c:14]([N+:15](=[O:16])[O-:17])[cH:18]1>>[CH3:1][c:2]1[cH:3][cH:4][cH:5][n:6][c:7]1-[c:8]1[cH:9][n:10][c:11]([C:12]#[N:13])[c:14]([N+:15](=[O:16])[O-:17])[cH:18]1
Cc1cccn[c]1[Zn+].N#Cc1ncc(Br)cc1[N+](=O)[O-]
Cc1cccnc1-c1cnc(C#N)c([N+](=O)[O-])c1
null
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1
C1CCOC1
C-C Coupling
OtherReaction
e4ecd4c8f01d2effb96acd4b7efc6dcca828274ea1bedd77506f1b8e3573c914
48892094855745f5c51f8910c27ce7c101e08ad3f9da2a58d5512e3d9c1b432f
c1ccc(-c2cccnc2)nc1
Br-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[c:4]:[#7;a:5]:[c:6]:1.[C;D1;H3:7]-[c:8](:[c:9]):[c;H0;D3;+0:10](-[Zn+]):[#7;a:11]:[c:12]>>[C;D1;H3:7]-[c:8](:[c:9]):[c;H0;D3;+0:10](-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[c:4]:[#7;a:5]:[c:6]:1):[#7;a:11]:[c:12]
88
[{"value": 88.0, "product": "CC=1C(=NC=CC1)C=1C=C(C(=NC1)C#N)[N+](=O)[O-]", "details": "PERCENTYIELD", "is_desired": false}, {"value": 87.8, "product": "CC=1C(=NC=CC1)C=1C=C(C(=NC1)C#N)[N+](=O)[O-]", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Heat a solution of 5-bromo-3-nitropyridine-2-carbonitrile (228 mg, 1.0 mmol), tetrakis(triphenylphosphine)palladium(0) (15 mg), 3-methyl-2-pyridylzinc bromide (0.5 M in THF, 3 mL, 1.5 mmol) in THF (5 mL) to 60° C. for 2 hours. Cool the solution and partition between ethyl acetate (10 mL) and saturated aqueous NaHCO3 (1...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
c1ccncc1.c1ccncc1
c1ccncc1.c1ccncc1
c1ccncc1.c1ccncc1
Br-.Zn
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.C1CCOC1
null
null
Cc1cccn[c]1[Zn+].N#Cc1ncc(Br)cc1[N+](=O)[O-]>C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.C1CCOC1>Cc1cccnc1-c1cnc(C#N)c([N+](=O)[O-])c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c77edee4a9fb4053b89ebe1c870aac40
Cc1cccnc1-c1cnc(C#N)c([N+](=O)[O-])c1>>Cc1cccnc1-c1cnc(C(N)=O)c(N)c1
CC=1C(=NC=CC1)C=1C=C(C(=NC1)C#N)[N+](=O)[O-].[Cl-].[Ca+2].[Cl-].C(C)O>>NC=1C(=NC=C(C1)C1=NC=CC=C1C)C(=O)N
[O-][N+:16](=[O:14])[c:15]1[c:11]([C:12]#[N:13])[n:10][cH:9][c:8](-[c:7]2[c:2]([CH3:1])[cH:3][cH:4][cH:5][n:6]2)[cH:17]1>>[CH3:1][c:2]1[cH:3][cH:4][cH:5][n:6][c:7]1-[c:8]1[cH:9][n:10][c:11]([C:12]([NH2:13])=[O:14])[c:15]([NH2:16])[cH:17]1
Cc1cccnc1-c1cnc(C#N)c([N+](=O)[O-])c1
Cc1cccnc1-c1cnc(C(N)=O)c(N)c1
null
[Fe]
O
Functional Group Interconversion
OtherReaction
ede7d2a6ee11f3b3697b1dfb480a8f492854589e148f2058b38ac2e2cd797a36
cb5481c22f68622a17796d4a172dd074a4fb2bd7f9c138bcaa93b97fc12e084f
c1ccc(-c2cccnc2)nc1
[N;H0;D1;+0:1]#[C;H0;D2;+0:2]-[c:3](:[#7;a:4]:[c:5]):[c:6](-[N+;H0;D3:7](-[O-])=[O;H0;D1;+0:8]):[c:9]>>[NH2;D1;+0:1]-[C;H0;D3;+0:2](=[O;H0;D1;+0:8])-[c:3](:[#7;a:4]:[c:5]):[c:6](-[NH2;D1;+0:7]):[c:9]
94
[{"value": 94.0, "product": "NC=1C(=NC=C(C1)C1=NC=CC=C1C)C(=O)N", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Heat a solution of 5-(3-methyl(2-pyridyl))-3-nitropyridine-2-carbonitrile (1 g, 4.1 mmol), iron (2.3 g, 40 mmol) and calcium chloride (560 mg, 5 mmol) in ethanol (15 mL) and water (4 mL) to reflux for 1 hour. Cool the mixture, filter through Celite and wash with ethyl acetate. Evaporate the filtrate and re-dissolve the...
10.6084/m9.figshare.5104873.v1
null
Nitrile.Nitro group
Primary amide.Primary amine
null
null
c1ccncc1.c1ccncc1
Other
[Fe].O
null
null
Cc1cccnc1-c1cnc(C#N)c([N+](=O)[O-])c1>[Fe].O>Cc1cccnc1-c1cnc(C(N)=O)c(N)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a37a88c4ed6045039b710a3512e968d7
Cc1cccnc1-c1cnc(C(N)=O)c(N)c1.FC(F)(F)c1ccc(Nc2nc(CN3CCCC3)nc3cc(-c4ncccc4C(F)(F)F)ccc23)cc1>>Cc1cccnc1-c1cnc2c(Nc3ccc(C(F)(F)F)cc3)nc(CN3CCCC3)nc2c1
N1(CCCC1)CC1=NC2=CC(=CC=C2C(=N1)NC1=CC=C(C=C1)C(F)(F)F)C1=NC=CC=C1C(F)(F)F.NC=1C(=NC=C(C1)C1=NC=CC=C1C)C(=O)N>>CC=1C(=NC=CC1)C1=CC=2N=C(N=C(C2N=C1)NC1=CC=C(C=C1)C(F)(F)F)CN1CCCC1
NC(=O)c1c(N)c[c:8](-[c:7]2[c:2]([CH3:1])[cH:3][cH:4][cH:5][n:6]2)[cH:9][n:10]1.FC(F)(F)c1cccnc1-c1cc[c:11]2[c:12]([NH:13][c:14]3[cH:15][cH:16][c:17]([C:18]([F:19])([F:20])[F:21])[cH:22][cH:23]3)[n:24][c:25]([CH2:26][N:27]3[CH2:28][CH2:29][CH2:30][CH2:31]3)[n:32][c:33]2[cH:34]1>>[CH3:1][c:2]1[cH:3][cH:4][cH:5][n:6][c:7]...
Cc1cccnc1-c1cnc(C(N)=O)c(N)c1.FC(F)(F)c1ccc(Nc2nc(CN3CCCC3)nc3cc(-c4ncccc4C(F)(F)F)ccc23)cc1
Cc1cccnc1-c1cnc2c(Nc3ccc(C(F)(F)F)cc3)nc(CN3CCCC3)nc2c1
null
null
null
Miscellaneous
OtherReaction
3fa4615a74505ac221315fc120db2d1bd3ef7488a92e7ae41a1b3502c3a29c1d
152ebe6d56cfc57e37cbb47d883f614870fc78ae305247312422e940fef02ee9
c1ccc(Nc2nc(CN3CCCC3)nc3cc(-c4ccccn4)cnc23)cc1
F-C(-F)(-F)-c1:c:c:c:n:c:1-c1:[cH;D2;+0:1]:[c:2]2:[#7;a:3]:[c:4]:[#7;a:5]:[c:6](-[#7:7]):[c;H0;D3;+0:8]:2:c:c:1.N-C(=O)-c1:[n;H0;D2;+0:9]:[c:10]:[c;H0;D3;+0:11](-[c:12](:[c:13]):[#7;a:14]:[c:15]):c:c:1-N>>[#7:7]-[c:6]1:[#7;a:5]:[c:4]:[#7;a:3]:[c:2]2:[cH;D2;+0:1]:[c;H0;D3;+0:11](-[c:12](:[c:13]):[#7;a:14]:[c:15]):[c:10]...
null
[]
null
null
null
null
The title compound is prepared from 3-amino-5-(3-methyl(2-pyridyl))pyridine-2-carboxamide in a manner analogous to that used for the preparation of [2-pyrrolidin-1-ylmethyl-7-(3-trifluoromethyl-pyridin-2-yl)-quinazolin-4-yl]-(4-trifluoromethyl-phenyl)-amine (Example 2.A, steps 6 to 9). Conditions: See reaction.notes.pr...
10.6084/m9.figshare.5104873.v1
null
Trifluoro group.Primary amide.Primary amine
null
c1ccncc1.c1ccncc1.c1ccc2ncncc2c1
c1cnc2cncnc2c1
c1ccncc1.c1ccccc1.c1cnc2cncnc2c1.C1CC[NH]C1
HF
null
null
null
Cc1cccnc1-c1cnc(C(N)=O)c(N)c1.FC(F)(F)c1ccc(Nc2nc(CN3CCCC3)nc3cc(-c4ncccc4C(F)(F)F)ccc23)cc1>>Cc1cccnc1-c1cnc2c(Nc3ccc(C(F)(F)F)cc3)nc(CN3CCCC3)nc2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d6813fe288124993a7c918a7f8a55b39
Cc1ccc(B(O)O)cc1.FC(F)(F)c1cccnc1Cl>>Cc1ccc(-c2ncccc2C(F)(F)F)cc1
ClC1=NC=CC=C1C(F)(F)F.B(C=1C=CC(=CC1)C)(O)O.C(=O)([O-])[O-].[Na+].[Na+]>>C1(=CC=C(C=C1)C1=NC=CC=C1C(F)(F)F)C
OB(O)[c:5]1[cH:4][cH:3][c:2]([CH3:1])[cH:17][cH:16]1.Cl[c:6]1[n:7][cH:8][cH:9][cH:10][c:11]1[C:12]([F:13])([F:14])[F:15]>>[CH3:1][c:2]1[cH:3][cH:4][c:5](-[c:6]2[n:7][cH:8][cH:9][cH:10][c:11]2[C:12]([F:13])([F:14])[F:15])[cH:16][cH:17]1
Cc1ccc(B(O)O)cc1.FC(F)(F)c1cccnc1Cl
Cc1ccc(-c2ncccc2C(F)(F)F)cc1
null
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1
COC
C-C Coupling
Suzuki coupling with boronic acids
07e9b6e71d806aa92d4573f3838e77c7c8344de3e5d5735ebdb5fc6862ebf27d
08d2969413ef1a2cd5b43667268ba178160c7b55545bf48018e31f2b019632ec
c1ccc(-c2ccccn2)cc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](-[C:5](-[F;D1;H0:6])(-[F;D1;H0:7])-[F;D1;H0:8]):[c:9].O-B(-O)-[c;H0;D3;+0:10](:[c:11]:[c:12]):[c:13]:[c:14]>>[F;D1;H0:6]-[C:5](-[F;D1;H0:7])(-[F;D1;H0:8])-[c:4](:[c:9]):[c;H0;D3;+0:1](-[c;H0;D3;+0:10](:[c:11]:[c:12]):[c:13]:[c:14]):[#7;a:2]:[c:3]
null
[]
80
CELSIUS
8
HOUR
To a de-gassed mixture of 2-chloro-3-(trifluoromethyl)-pyridine (70.1 mmol), p-tolylboronic acid (70.6 mmol), and 2M Na2CO3 (175.0 mmol), in dimethyl ether (DME; 200 mL) under nitrogen add Pd(PPh3)4 (2.8 mmol). Stir the mixture at 80° C. overnight, concentrate, and extract with EtOAc. Dry over Na2SO4, concentrate under...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Boronic acid
null
c1ccccc1.c1ccncc1
c1ccccc1.c1ccncc1
c1ccccc1.c1ccncc1
HCl.B
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.COC
80
8
Cc1ccc(B(O)O)cc1.FC(F)(F)c1cccnc1Cl>C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.COC>Cc1ccc(-c2ncccc2C(F)(F)F)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a74422cb03ef40a2afe09f0d7d70af8c
Cc1ccc(-c2ncccc2C(F)(F)F)cc1.O=[N+]([O-])O>>Cc1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
C1(=CC=C(C=C1)C1=NC=CC=C1C(F)(F)F)C.[N+](=O)(O)[O-]>>CC1=C(C=C(C=C1)C1=NC=CC=C1C(F)(F)F)[N+](=O)[O-]
[CH3:1][c:2]1[cH:3][cH:4][c:5](-[c:6]2[n:7][cH:8][cH:9][cH:10][c:11]2[C:12]([F:13])([F:14])[F:15])[cH:16][cH:17]1.O[N+:18](=[O:19])[O-:20]>>[CH3:1][c:2]1[cH:3][cH:4][c:5](-[c:6]2[n:7][cH:8][cH:9][cH:10][c:11]2[C:12]([F:13])([F:14])[F:15])[cH:16][c:17]1[N+:18](=[O:19])[O-:20]
Cc1ccc(-c2ncccc2C(F)(F)F)cc1.O=[N+]([O-])O
Cc1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
null
null
OS(=O)(=O)O
Functional Group Addition
Aromatic nitration with HNO3
53848b8b2bb4e867226e49db2e60519b24be9379900e3ad7c56af54fe8fde7a5
ddce49825c02b8965f10c8d99e3c841d26e1f136da6037b417c09313e6d73097
c1ccc(-c2ccccn2)cc1
O-[N+;H0;D3:1](-[O;-;D1;H0:2])=[O;D1;H0:3].[C;D1;H3:4]-[c:5](:[c:6]):[cH;D2;+0:7]:[c:8]:[c:9]>>[C;D1;H3:4]-[c:5](:[c:6]):[c;H0;D3;+0:7](-[N+;H0;D3:1](-[O;-;D1;H0:2])=[O;D1;H0:3]):[c:8]:[c:9]
null
[]
null
null
60
MINUTE
To a solution of 2-p-tolyl-3-trifluoromethyl-pyridine (8.4 mmol) in H2SO4 (6 mL) cautiously add fuming HNO3 (2 ml). Stir the mixture for 60 minutes at room temperature. Pour the mixture onto ice-water (30 mL), extract with EtOAc, neutralize with 1 N NaOH, dry over Na2SO4, and concentrate under vacuum to obtain 2-(4-met...
10.6084/m9.figshare.5104873.v1
null
Nitrate
Nitro group
c1ccccc1
c1ccccc1
c1ccccc1.c1ccncc1
HO-
OS(=O)(=O)O
null
1
Cc1ccc(-c2ncccc2C(F)(F)F)cc1.O=[N+]([O-])O>OS(=O)(=O)O>Cc1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3ae2729437fd4a318279beede51d1186
NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]>>NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N
[N+](=O)([O-])C1=C(C(=O)N)C=CC(=C1)C1=NC=CC=C1C(F)(F)F>>NC1=C(C(=O)N)C=CC(=C1)C1=NC=CC=C1C(F)(F)F
O=[N+:20]([O-])[c:19]1[c:4]([C:2]([NH2:1])=[O:3])[cH:5][cH:6][c:7](-[c:8]2[n:9][cH:10][cH:11][cH:12][c:13]2[C:14]([F:15])([F:16])[F:17])[cH:18]1>>[NH2:1][C:2](=[O:3])[c:4]1[cH:5][cH:6][c:7](-[c:8]2[n:9][cH:10][cH:11][cH:12][c:13]2[C:14]([F:15])([F:16])[F:17])[cH:18][c:19]1[NH2:20]
NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N
null
[Pd]
C(C)O
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccc(-c2ccccn2)cc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]-[C:5](-[N;D1;H2:6])=[O;D1;H0:7]>>[N;D1;H2:6]-[C:5](=[O;D1;H0:7])-[c:4]:[c:2](-[NH2;D1;+0:1]):[c:3]
null
[]
null
null
16
HOUR
Hydrogenate 2-nitro-4-(3-trifluoromethyl-pyridin-2-yl)-benzamide (1.0 g, 0.0032 mol) with 50 psi of H2 and 100 mg of 10% Pd/C in ethanol. After 16 hours, filter the mixture through celite and concentrate under reduced pressure to give 2-amino-4-(3-trifluoromethyl-pyridin-2-yl)-benzamide as a solid. Conditions: See reac...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccccc1.c1ccncc1
Other
[Pd].C(C)O
null
16
NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]>[Pd].C(C)O>NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-85afb19869af47839581787a5e3a7eae
COC(CCl)(OC)OC.NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N>>O=c1[nH]c(CCl)nc2cc(-c3ncccc3C(F)(F)F)ccc12
NC1=C(C(=O)N)C=CC(=C1)C1=NC=CC=C1C(F)(F)F.ClCC(OC)(OC)OC>>ClCC1=NC2=CC(=CC=C2C(N1)=O)C1=NC=CC=C1C(F)(F)F
CO[C:4](OC)(OC)[CH2:5][Cl:6].[O:1]=[C:2]([NH2:3])[c:23]1[c:8]([NH2:7])[cH:9][c:10](-[c:11]2[n:12][cH:13][cH:14][cH:15][c:16]2[C:17]([F:18])([F:19])[F:20])[cH:21][cH:22]1>>[O:1]=[c:2]1[nH:3][c:4]([CH2:5][Cl:6])[n:7][c:8]2[cH:9][c:10](-[c:11]3[n:12][cH:13][cH:14][cH:15][c:16]3[C:17]([F:18])([F:19])[F:20])[cH:21][cH:22][c...
COC(CCl)(OC)OC.NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N
O=c1[nH]c(CCl)nc2cc(-c3ncccc3C(F)(F)F)ccc12
null
null
null
Aromatic Heterocycle Formation
OtherReaction
292ab66b88620748fa9d06e6e4d9b67ede3a8fd233d74022944407012fccec37
7ad6d407a4f6c8573e2bc724851922f3f76bd08d2e3d3a3ddf0a52cbc9de261c
O=c1[nH]cnc2cc(-c3ccccn3)ccc12
C-O-[C;H0;D4;+0:1](-O-C)(-O-C)-[C:2]-[Cl;D1;H0:3].[NH2;D1;+0:4]-[C;H0;D3;+0:5](=[O;D1;H0:6])-[c:7](:[c:8]):[c:9](-[NH2;D1;+0:10]):[c:11]>>[Cl;D1;H0:3]-[C:2]-[c;H0;D3;+0:1]1:[n;H0;D2;+0:10]:[c:9](:[c:11]):[c:7](:[c:8]):[c;H0;D3;+0:5](=[O;D1;H0:6]):[nH;D2;+0:4]:1
null
[]
null
null
null
null
Heat a solution of 2-amino-4-(3-trifluoromethyl-pyridin-2-yl)-benzamide (100 mg, 0.356 mmol) in 2-chloro-1,1,1-trimethoxyethane (bp 138° C.) at 130° C. for 4 hours. Concentrate the mixture under reduced pressure to give 2-chloromethyl-7-(3-trifluoromethyl-pyridin-2-yl)-3H-quinazolin-4-one as an oil which crystallizes o...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether.Ether.Primary amide.Primary amine
null
c1ccccc1
c1ccc2cncnc2c1
c1ccc2cncnc2c1.c1ccncc1
HO-
null
null
null
COC(CCl)(OC)OC.NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N>>O=c1[nH]c(CCl)nc2cc(-c3ncccc3C(F)(F)F)ccc12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3a01df7e0ea84826859deaf88f3393f7
CC(C)[O][Na].FC(F)(F)c1ccc(Nc2nc(CCl)nc3cc(-c4ncccc4C(F)(F)F)ccc23)cc1>>CC(C)OCc1nc(Nc2ccc(C(F)(F)F)cc2)c2ccc(-c3ncccc3C(F)(F)F)cc2n1
Cl.ClCC1=NC2=CC(=CC=C2C(=N1)NC1=CC=C(C=C1)C(F)(F)F)C1=NC=CC=C1C(F)(F)F.O([Na])C(C)C>>C(C)(C)OCC1=NC2=CC(=CC=C2C(=N1)NC1=CC=C(C=C1)C(F)(F)F)C1=NC=CC=C1C(F)(F)F
[Na][O:4][CH:2]([CH3:1])[CH3:3].Cl[CH2:5][c:6]1[n:7][c:8]([NH:9][c:10]2[cH:11][cH:12][c:13]([C:14]([F:15])([F:16])[F:17])[cH:18][cH:19]2)[c:20]2[cH:21][cH:22][c:23](-[c:24]3[n:25][cH:26][cH:27][cH:28][c:29]3[C:30]([F:31])([F:32])[F:33])[cH:34][c:35]2[n:36]1>>[CH3:1][CH:2]([CH3:3])[O:4][CH2:5][c:6]1[n:7][c:8]([NH:9][c:1...
CC(C)[O][Na].FC(F)(F)c1ccc(Nc2nc(CCl)nc3cc(-c4ncccc4C(F)(F)F)ccc23)cc1
CC(C)OCc1nc(Nc2ccc(C(F)(F)F)cc2)c2ccc(-c3ncccc3C(F)(F)F)cc2n1
null
null
C(C)(C)O
Heteroatom Alkylation and Arylation
OtherReaction
3dd6ea90858eede84ece2f60931b760bd509d5f421f2feb2b0fe7a2c006d84f0
62c7c72c35b09d63ca1131e6cd8c0b88a31e29901d660456b77319cfd78354c7
c1ccc(Nc2ncnc3cc(-c4ccccn4)ccc23)cc1
Cl-[CH2;D2;+0:1]-[c:2](:[#7;a:3]:[c:4]):[#7;a:5]:[c:6].[C;D1;H3:7]-[C:8](-[C;D1;H3:9])-[O;H0;D2;+0:10]-[Na]>>[C;D1;H3:7]-[C:8](-[C;D1;H3:9])-[O;H0;D2;+0:10]-[CH2;D2;+0:1]-[c:2](:[#7;a:3]:[c:4]):[#7;a:5]:[c:6]
null
[]
60
CELSIUS
5
HOUR
To a suspension of [2-chloromethyl-7-(3-trifluoromethyl-pyridin-2-yl)-quinazolin-4-yl]-(4-trifluoromethyl-phenyl)-amine hydrochloride (1.9 g, 0.0037 mol) in dry isopropanol (100 mL), add 20 equivalents of NaO-i-Pr (prepared from Na and isopropanol). Stir the pale yellow mixture at 60° C. for 5 hours, cool and evaporate...
10.6084/m9.figshare.5104873.v1
null
Primary halide
Ether
null
null
c1ccccc1.c1ccc2ncncc2c1.c1ccncc1
Na
C(C)(C)O
60
5
CC(C)[O][Na].FC(F)(F)c1ccc(Nc2nc(CCl)nc3cc(-c4ncccc4C(F)(F)F)ccc23)cc1>C(C)(C)O>CC(C)OCc1nc(Nc2ccc(C(F)(F)F)cc2)c2ccc(-c3ncccc3C(F)(F)F)cc2n1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b3d32619db8c454f91c6ff0ecdea30c6
CCOC(=O)CCBr.OCc1ccccc1>>O=C(O)CCOCc1ccccc1
O.[H-].[Na+].C(C1=CC=CC=C1)O.BrCCC(=O)OCC>>C(C1=CC=CC=C1)OCCC(=O)O
CC[O:3][C:2](=[O:1])[CH2:4][CH2:5]Br.[OH:6][CH2:7][c:8]1[cH:9][cH:10][cH:11][cH:12][cH:13]1>>[O:1]=[C:2]([OH:3])[CH2:4][CH2:5][O:6][CH2:7][c:8]1[cH:9][cH:10][cH:11][cH:12][cH:13]1
CCOC(=O)CCBr.OCc1ccccc1
O=C(O)CCOCc1ccccc1
null
null
[OH-].[Na+].C1(=CC=CC=C1)C.CO.C(C)(=O)OCC
Heteroatom Alkylation and Arylation
OtherReaction
649e704edbb364f9da7d07cbe4234c4a92fb1da39cfc9c27b4b5f45f135ea332
618df49e449d2d4d71a5c69761039aa60d2846715c5b4fde87b9028fc160ed45
c1ccccc1
Br-[CH2;D2;+0:1]-[C:2]-[C:3](=[O;D1;H0:4])-[O;H0;D2;+0:5]-C-C.[OH;D1;+0:6]-[C:7]-[c:8]>>[O;D1;H0:4]=[C:3](-[OH;D1;+0:5])-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:6]-[C:7]-[c:8]
34.2
[{"value": 34.0, "product": "C(C1=CC=CC=C1)OCCC(=O)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 34.2, "product": "C(C1=CC=CC=C1)OCCC(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
Add sodium hydride (2.22 g, 60% dispersion in mineral oil, 55.4 mmol) in small portions to a cold (0° C.) solution of benzyl alcohol (4.0 g, 37 mmol) in toluene (100 mL). Add ethyl 3-bromopropionate (8.0 g, 44 mmol) dropwise to the mixture, allow the resulting solution to warm to room temperature and stir for 1 hour. Q...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Primary alcohol
Carboxylic acid.Ether
null
null
c1ccccc1
HBr
[OH-].[Na+].C1(=CC=CC=C1)C.CO.C(C)(=O)OCC
null
1
CCOC(=O)CCBr.OCc1ccccc1>[OH-].[Na+].C1(=CC=CC=C1)C.CO.C(C)(=O)OCC>O=C(O)CCOCc1ccccc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f0d3d7aa5188492bb4f3d74489d05f49
COCCCC(=O)Cl.NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N.c1ccncc1>>Oc1nc(CCCOCc2ccccc2)nc2cc(-c3ncccc3C(F)(F)F)ccc12
[OH-].[Na+].NC1=C(C(=O)N)C=CC(=C1)C1=NC=CC=C1C(F)(F)F.N1=CC=CC=C1.COCCCC(=O)Cl.C1CCOC1>>C(C1=CC=CC=C1)OCCCC1=NC2=CC(=CC=C2C(=N1)O)C1=NC=CC=C1C(F)(F)F
O=[C:4](Cl)[CH2:5][CH2:6][CH2:7][O:8][CH3:9].[O:1]=[C:2]([NH2:3])[c:32]1[c:17]([NH2:16])[cH:18][c:19](-[c:20]2[n:21][cH:22][cH:23][cH:24][c:25]2[C:26]([F:27])([F:28])[F:29])[cH:30][cH:31]1.n1[cH:11][cH:12][cH:13][cH:14][cH:15]1>>[OH:1][c:2]1[n:3][c:4]([CH2:5][CH2:6][CH2:7][O:8][CH2:9][c:10]2[cH:11][cH:12][cH:13][cH:14]...
COCCCC(=O)Cl.NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N.c1ccncc1
Oc1nc(CCCOCc2ccccc2)nc2cc(-c3ncccc3C(F)(F)F)ccc12
null
null
null
Aromatic Heterocycle Formation
OtherReaction
b34f8adda3824855b490c3a1513f656f30d682b61c7e67001560ba564ef0b0c2
d626de740818142cd15e2d01aa83dff506457ddae8038f340ed9da5ea4e481c5
c1ccc(COCCCc2ncc3ccc(-c4ccccn4)cc3n2)cc1
Cl-[C;H0;D3;+0:1](=O)-[C:2]-[C:3]-[C:4]-[#8:5]-[CH3;D1;+0:6].[NH2;D1;+0:7]-[c:8](:[c:9]):[c:10](-[C;H0;D3;+0:11](-[NH2;D1;+0:12])=[O;H0;D1;+0:13]):[c:14].[c:15]1:[c:16]:[c:17]:[cH;D2;+0:18]:n:[cH;D2;+0:19]:1>>[OH;D1;+0:13]-[c;H0;D3;+0:11]1:[n;H0;D2;+0:12]:[c;H0;D3;+0:1](-[C:2]-[C:3]-[C:4]-[#8:5]-[CH2;D2;+0:6]-[c:20]2:[...
null
[]
null
null
20
MINUTE
To a solution of 2-amino-4-(3-trifluoromethyl-pyridin-2-yl)-benzamide (3.56 mmol) and pyridine (3.91 mmol) in THF (20 ml), add 4-methoxy-butyryl chloride (3.91 mmol). Stir the mixture 20 minutes at room temperature, add 20 ml of 20% NaOH, stir for 60 minutes at 50° C. Concentrate, add water, filter, acidify to pH=6, co...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Ether.Primary amide.Primary amine
Ether.Aromatic alcohol
c1ccccc1.c1ccncc1
c1ccccc1.c1ccc2ncncc2c1
c1ccccc1.c1ccc2ncncc2c1.c1ccncc1
HCl
null
null
0.333333
COCCCC(=O)Cl.NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N.c1ccncc1>>Oc1nc(CCCOCc2ccccc2)nc2cc(-c3ncccc3C(F)(F)F)ccc12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-76f21bcd99754d0cb5b8bcefa0ae7101
NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N.O=C(Cl)CCCOCc1ccccc1>>Oc1nc(CCCOCc2ccccc2)nc2cc(-c3ncccc3C(F)(F)F)ccc12
[OH-].[Na+].NC1=C(C(=O)N)C=CC(=C1)C1=NC=CC=C1C(F)(F)F.N1=CC=CC=C1.C(C1=CC=CC=C1)OCCCC(=O)Cl>>C(C1=CC=CC=C1)OCCCC1=NC2=CC(=CC=C2C(=N1)O)C1=NC=CC=C1C(F)(F)F
[O:1]=[C:2]([NH2:3])[c:32]1[c:17]([NH2:16])[cH:18][c:19](-[c:20]2[n:21][cH:22][cH:23][cH:24][c:25]2[C:26]([F:27])([F:28])[F:29])[cH:30][cH:31]1.O=[C:4](Cl)[CH2:5][CH2:6][CH2:7][O:8][CH2:9][c:10]1[cH:11][cH:12][cH:13][cH:14][cH:15]1>>[OH:1][c:2]1[n:3][c:4]([CH2:5][CH2:6][CH2:7][O:8][CH2:9][c:10]2[cH:11][cH:12][cH:13][cH...
NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N.O=C(Cl)CCCOCc1ccccc1
Oc1nc(CCCOCc2ccccc2)nc2cc(-c3ncccc3C(F)(F)F)ccc12
null
null
C1CCOC1
Aromatic Heterocycle Formation
OtherReaction
421874b4cd55eaa20f24b1cd7ba94b5870b5c4e9b00f756449eff425c4e3a153
d5ef1961d36ab2d05e773eb9e606a89406d1ee5463b381ad4c7037e46428ccb9
c1ccc(COCCCc2ncc3ccc(-c4ccccn4)cc3n2)cc1
Cl-[C;H0;D3;+0:1](=O)-[C:2]-[C:3].[NH2;D1;+0:4]-[c:5](:[c:6]):[c:7](-[C;H0;D3;+0:8](-[NH2;D1;+0:9])=[O;H0;D1;+0:10]):[c:11]>>[C:3]-[C:2]-[c;H0;D3;+0:1]1:[n;H0;D2;+0:4]:[c:5](:[c:6]):[c:7](:[c:11]):[c;H0;D3;+0:8](-[OH;D1;+0:10]):[n;H0;D2;+0:9]:1
null
[]
null
null
20
MINUTE
To a solution of 2-amino-4-(3-trifluoromethyl-pyridin-2-yl)-benzamide (3.56 mmol) and pyridine (3.91 mmol) in THF (20 ml) add 4-benzyloxy-butyryl chloride (3.91 mmol). Stir the mixture 20 minutes at room temperature, add 20 ml of 20% NaOH, stir for 60 minutes at 50° C. Concentrate, add water, filter, acidify to pH=6, c...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amide.Primary amine
Aromatic alcohol
c1ccccc1
c1ccc2ncncc2c1
c1ccccc1.c1ccc2ncncc2c1.c1ccncc1
HCl
C1CCOC1
null
0.333333
NC(=O)c1ccc(-c2ncccc2C(F)(F)F)cc1N.O=C(Cl)CCCOCc1ccccc1>C1CCOC1>Oc1nc(CCCOCc2ccccc2)nc2cc(-c3ncccc3C(F)(F)F)ccc12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-634b8a8802314e3aae7783e948e46790
COc1ccc(B(O)O)cn1.FC(F)(F)c1cccnc1Cl>>COc1ccc(-c2ncccc2C(F)(F)F)cn1
ClC1=NC=CC=C1C(F)(F)F.COC1=NC=C(C=C1)B(O)O.C([O-])([O-])=O.[K+].[K+]>>COC1=CC=C(C=N1)C1=NC=CC=C1C(F)(F)F
OB(O)[c:6]1[cH:5][cH:4][c:3]([O:2][CH3:1])[n:18][cH:17]1.Cl[c:7]1[n:8][cH:9][cH:10][cH:11][c:12]1[C:13]([F:14])([F:15])[F:16]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6](-[c:7]2[n:8][cH:9][cH:10][cH:11][c:12]2[C:13]([F:14])([F:15])[F:16])[cH:17][n:18]1
COc1ccc(B(O)O)cn1.FC(F)(F)c1cccnc1Cl
COc1ccc(-c2ncccc2C(F)(F)F)cn1
null
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1
C1(=CC=CC=C1)C
C-C Coupling
Suzuki coupling with boronic acids
2e12f1697d123c35af029842984dda76c08cdd06401f05924c6b1363bf342af9
08d2969413ef1a2cd5b43667268ba178160c7b55545bf48018e31f2b019632ec
c1ccc(-c2cccnc2)nc1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](-[C:5](-[F;D1;H0:6])(-[F;D1;H0:7])-[F;D1;H0:8]):[c:9].O-B(-O)-[c;H0;D3;+0:10]1:[c:11]:[#7;a:12]:[c:13]:[c:14]:[c:15]:1>>[F;D1;H0:6]-[C:5](-[F;D1;H0:7])(-[F;D1;H0:8])-[c:4](:[c:9]):[c;H0;D3;+0:1](-[c;H0;D3;+0:10]1:[c:11]:[#7;a:12]:[c:13]:[c:14]:[c:15]:1):[#7;a:2]:[c:3]
95
[{"value": 95.0, "product": "COC1=CC=C(C=N1)C1=NC=CC=C1C(F)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 94.8, "product": "COC1=CC=C(C=N1)C1=NC=CC=C1C(F)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Heat a mixture of 2-chloro-3-trifluoromethylpyridine (37 g, 0.2 mol), 2-methoxypyridine-5-boronic acid (32 g, 0.21 mol), tetrakis(triphenylphosphine)palladium(0) (9 g, 7 mmol) and 2M potassium carbonate (150 mL) in toluene (500 mL) under a nitrogen atmosphere at 90° C. for 8 hours. Cool the reaction mixture and separat...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Boronic acid
null
c1ccncc1.c1ccncc1
c1ccncc1.c1ccncc1
c1ccncc1.c1ccncc1
HCl.B
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.C1(=CC=CC=C1)C
null
null
COc1ccc(B(O)O)cn1.FC(F)(F)c1cccnc1Cl>C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.C1(=CC=CC=C1)C>COc1ccc(-c2ncccc2C(F)(F)F)cn1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-19017cea450249218e3f99d4c973dc72
COc1ccc(-c2ncccc2C(F)(F)F)cn1>>O=c1ccc(-c2ncccc2C(F)(F)F)c[nH]1
COC1=CC=C(C=N1)C1=NC=CC=C1C(F)(F)F>>FC(C=1C(=NC=CC1)C1=CNC(C=C1)=O)(F)F
C[O:1][c:2]1[cH:3][cH:4][c:5](-[c:6]2[n:7][cH:8][cH:9][cH:10][c:11]2[C:12]([F:13])([F:14])[F:15])[cH:16][n:17]1>>[O:1]=[c:2]1[cH:3][cH:4][c:5](-[c:6]2[n:7][cH:8][cH:9][cH:10][c:11]2[C:12]([F:13])([F:14])[F:15])[cH:16][nH:17]1
COc1ccc(-c2ncccc2C(F)(F)F)cn1
O=c1ccc(-c2ncccc2C(F)(F)F)c[nH]1
null
null
Br.CC(=O)O
Miscellaneous
OtherReaction
ffbb4288e7102e6f227d930be4a9510dc9e13ff3142954fd43347db64909ca58
291cad8b6dfbbd2c823b5c9d45efc37a166dc3454a9f151ac48cb357f4bc155f
O=c1ccc(-c2ccccn2)c[nH]1
C-[O;H0;D2;+0:1]-[c;H0;D3;+0:2]1:[c:3]:[c:4]:[c:5]:[c:6]:[n;H0;D2;+0:7]:1>>[O;H0;D1;+0:1]=[c;H0;D3;+0:2]1:[c:3]:[c:4]:[c:5]:[c:6]:[nH;D2;+0:7]:1
93.7
[{"value": 93.0, "product": "FC(C=1C(=NC=CC1)C1=CNC(C=C1)=O)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 93.7, "product": "FC(C=1C(=NC=CC1)C1=CNC(C=C1)=O)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
Heat 6′-Methoxy-3-trifluoromethyl-[2,3′]bipyridinyl (41 g, 0.16 mol) in 30% HBr/AcOH (100 mL) to reflux for 1 hour. Cool the mixture, filter and wash the precipitate with ether (100 mL). Transfer the precipitate into 10M sodium hydroxide (500 mL) and stir for 1 hour. Treat the solution with hydrochloric acid until the ...
10.6084/m9.figshare.5104873.v1
null
Ether
null
c1ccncc1
c1cccnc1
c1cccnc1.c1ccncc1
Other
Br.CC(=O)O
null
1
COc1ccc(-c2ncccc2C(F)(F)F)cn1>Br.CC(=O)O>O=c1ccc(-c2ncccc2C(F)(F)F)c[nH]1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-05492f6a96b7429db4e0da67867767ff
O=[N+]([O-])O.O=c1ccc(-c2ncccc2C(F)(F)F)c[nH]1>>O=c1[nH]cc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
FC(C=1C(=NC=CC1)C1=CNC(C=C1)=O)(F)F.[N+](=O)(O)[O-]>>[N+](=O)([O-])C1=CC(=CNC1=O)C1=NC=CC=C1C(F)(F)F
O[N+:18](=[O:19])[O-:20].[O:1]=[c:2]1[nH:3][cH:4][c:5](-[c:6]2[n:7][cH:8][cH:9][cH:10][c:11]2[C:12]([F:13])([F:14])[F:15])[cH:16][cH:17]1>>[O:1]=[c:2]1[nH:3][cH:4][c:5](-[c:6]2[n:7][cH:8][cH:9][cH:10][c:11]2[C:12]([F:13])([F:14])[F:15])[cH:16][c:17]1[N+:18](=[O:19])[O-:20]
O=[N+]([O-])O.O=c1ccc(-c2ncccc2C(F)(F)F)c[nH]1
O=c1[nH]cc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
null
null
S(O)(O)(=O)=O
Functional Group Addition
Aromatic nitration with HNO3
26a878e97e02b420c859859d3c94a295b28ee7e9c7a3a499b0358675c34410cd
ddce49825c02b8965f10c8d99e3c841d26e1f136da6037b417c09313e6d73097
O=c1ccc(-c2ccccn2)c[nH]1
O-[N+;H0;D3:1](-[O;-;D1;H0:2])=[O;D1;H0:3].[O;D1;H0:4]=[c:5]1:[#7;a:6]:[c:7]:[c:8]:[c:9]:[cH;D2;+0:10]:1>>[O;-;D1;H0:2]-[N+;H0;D3:1](=[O;D1;H0:3])-[c;H0;D3;+0:10]1:[c:9]:[c:8]:[c:7]:[#7;a:6]:[c:5]:1=[O;D1;H0:4]
92
[{"value": 92.0, "product": "[N+](=O)([O-])C1=CC(=CNC1=O)C1=NC=CC=C1C(F)(F)F", "details": "PERCENTYIELD", "is_desired": false}]
70
CELSIUS
null
null
To a solution of 3-trifluoromethyl-1′H-[2,3′]bipyridinyl-6′-one (25 g, 0.1 mol) in concentrated sulfuric acid (100 mL) at 0° C., add dropwise a solution of fuming nitric acid (35 mL) and concentrated sulfuric acid (10 mL). Heat the reaction mixture to 70° C. for 1 hour, cool and pour onto ice (500 mL). Filter the mixtu...
10.6084/m9.figshare.5104873.v1
null
Nitrate
Nitro group
c1cccnc1
c1cnccc1
c1cnccc1.c1ccncc1
HO-
S(O)(O)(=O)=O
70
null
O=[N+]([O-])O.O=c1ccc(-c2ncccc2C(F)(F)F)c[nH]1>S(O)(O)(=O)=O>O=c1[nH]cc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3648be0c925346ff99a238ce1ea29109
O=S(Cl)Cl.O=c1[nH]cc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]>>O=[N+]([O-])c1cc(-c2ncccc2C(F)(F)F)cnc1Cl
[N+](=O)([O-])C1=CC(=CNC1=O)C1=NC=CC=C1C(F)(F)F.S(=O)(Cl)Cl>>ClC1=C(C=C(C=N1)C1=NC=CC=C1C(F)(F)F)[N+](=O)[O-]
O=S(Cl)[Cl:20].O=[c:19]1[c:4]([N+:2](=[O:1])[O-:3])[cH:5][c:6](-[c:7]2[n:8][cH:9][cH:10][cH:11][c:12]2[C:13]([F:14])([F:15])[F:16])[cH:17][nH:18]1>>[O:1]=[N+:2]([O-:3])[c:4]1[cH:5][c:6](-[c:7]2[n:8][cH:9][cH:10][cH:11][c:12]2[C:13]([F:14])([F:15])[F:16])[cH:17][n:18][c:19]1[Cl:20]
O=S(Cl)Cl.O=c1[nH]cc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]
O=[N+]([O-])c1cc(-c2ncccc2C(F)(F)F)cnc1Cl
null
null
CN(C)C=O
Functional Group Interconversion
OtherReaction
ad993f9ce2ce60b71a2afb3182d5e182b0d0de1be8200a3f161e73174c9a6ebf
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccc(-c2cccnc2)nc1
Cl-S(=O)-[Cl;H0;D1;+0:1].O=[c;H0;D3;+0:2]1:[nH;D2;+0:3]:[c:4]:[c:5]:[c:6]:[c:7]:1-[#7;+:8]>>[#7;+:8]-[c:7]1:[c:6]:[c:5]:[c:4]:[n;H0;D2;+0:3]:[c;H0;D3;+0:2]:1-[Cl;H0;D1;+0:1]
93
[{"value": 93.0, "product": "ClC1=C(C=C(C=N1)C1=NC=CC=C1C(F)(F)F)[N+](=O)[O-]", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Heat a solution of 5′-nitro-3-trifluoromethyl-1′H[2,3′]bipyridinyl-6′-one (25 g, 0.088 mol), thionyl chloride (300 mL) and DMF (3 mL) to reflux for 4 hours. Remove the volatiles by rotary evaporation and partition the residue between ethyl acetate (350 mL) and saturated sodium bicarbonate solution (250 mL). Extract the...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1cnccc1
c1ccncc1
c1ccncc1.c1ccncc1
HCl
CN(C)C=O
null
null
O=S(Cl)Cl.O=c1[nH]cc(-c2ncccc2C(F)(F)F)cc1[N+](=O)[O-]>CN(C)C=O>O=[N+]([O-])c1cc(-c2ncccc2C(F)(F)F)cnc1Cl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-1135e8d12c4344768805a1fcbbf87482
O=[N+]([O-])c1cc(-c2ncccc2C(F)(F)F)cnc1Cl>>Nc1cc(-c2ncccc2C(F)(F)F)cnc1Cl
ClC1=C(C=C(C=N1)C1=NC=CC=C1C(F)(F)F)[N+](=O)[O-].[Cl-].[Ca+2].[Cl-]>>ClC1=C(C=C(C=N1)C1=NC=CC=C1C(F)(F)F)N
O=[N+:1]([O-])[c:2]1[cH:3][c:4](-[c:5]2[n:6][cH:7][cH:8][cH:9][c:10]2[C:11]([F:12])([F:13])[F:14])[cH:15][n:16][c:17]1[Cl:18]>>[NH2:1][c:2]1[cH:3][c:4](-[c:5]2[n:6][cH:7][cH:8][cH:9][c:10]2[C:11]([F:12])([F:13])[F:14])[cH:15][n:16][c:17]1[Cl:18]
O=[N+]([O-])c1cc(-c2ncccc2C(F)(F)F)cnc1Cl
Nc1cc(-c2ncccc2C(F)(F)F)cnc1Cl
null
[Fe]
O.C(C)O
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccc(-c2cccnc2)nc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4](-[Cl;D1;H0:5]):[#7;a:6]:[c:7]>>[Cl;D1;H0:5]-[c:4](:[#7;a:6]:[c:7]):[c:2](-[NH2;D1;+0:1]):[c:3]
85
[{"value": 85.0, "product": "ClC1=C(C=C(C=N1)C1=NC=CC=C1C(F)(F)F)N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 84.7, "product": "ClC1=C(C=C(C=N1)C1=NC=CC=C1C(F)(F)F)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of 6′-chloro-5′-nitro-3-trifluoromethyl-[2,3′]bipyridinyl (25 g, 0.082 mol) and calcium chloride (11 g, 0.1 mol) in ethanol (300 mL) and water (50 mL), add iron powder (45 g, 0.82 mol). Heat the solution to reflux for 1.5 hours, cool and filter through Celite. Concentrate the mixture under reduced pressur...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccncc1.c1ccncc1
Other
[Fe].O.C(C)O
null
null
O=[N+]([O-])c1cc(-c2ncccc2C(F)(F)F)cnc1Cl>[Fe].O.C(C)O>Nc1cc(-c2ncccc2C(F)(F)F)cnc1Cl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-269008a3e97d454a9e8ef3f4ef800056
CN(C)C=O.Nc1cc(-c2ncccc2C(F)(F)F)cnc1Cl.[NH4+]>>NC(=O)c1ncc(-c2ncccc2C(F)(F)F)cc1N
ClC1=C(C=C(C=N1)C1=NC=CC=C1C(F)(F)F)N.CN(C)C=O.[Cl-].[NH4+].[OH-].[NH4+]>>NC=1C(=NC=C(C1)C1=NC=CC=C1C(F)(F)F)C(=O)N
CN(C)[CH:2]=[O:3].Cl[c:4]1[n:5][cH:6][c:7](-[c:8]2[n:9][cH:10][cH:11][cH:12][c:13]2[C:14]([F:15])([F:16])[F:17])[cH:18][c:19]1[NH2:20].[NH4+:1]>>[NH2:1][C:2](=[O:3])[c:4]1[n:5][cH:6][c:7](-[c:8]2[n:9][cH:10][cH:11][cH:12][c:13]2[C:14]([F:15])([F:16])[F:17])[cH:18][c:19]1[NH2:20]
CN(C)C=O.Nc1cc(-c2ncccc2C(F)(F)F)cnc1Cl.[NH4+]
NC(=O)c1ncc(-c2ncccc2C(F)(F)F)cc1N
null
[C-]#N.[Zn+2].[C-]#N.C1(=CC=CC=C1)P([C-]1C=CC=C1)C1=CC=CC=C1.[C-]1(C=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Fe+2]
O
Acylation
OtherReaction
e1863fb77b18a4f8a4f6f62e441a7222b67756c377f9188d3bd53f6c3965f65f
e877213e19171755e0934a74438f863139f6bd24cdbe9c4b94ecbf55b1179c4e
c1ccc(-c2cccnc2)nc1
C-N(-C)-[CH;D2;+0:1]=[O;D1;H0:2].Cl-[c;H0;D3;+0:3](:[#7;a:4]:[c:5]):[c:6](-[N;D1;H2:7]):[c:8].[NH4+;D0:9]>>[N;D1;H2:7]-[c:6](:[c:8]):[c;H0;D3;+0:3](-[C;H0;D3;+0:1](-[NH2;D1;+0:9])=[O;D1;H0:2]):[#7;a:4]:[c:5]
90
[{"value": 90.0, "product": "NC=1C(=NC=C(C1)C1=NC=CC=C1C(F)(F)F)C(=O)N", "details": "PERCENTYIELD", "is_desired": false}]
0
CELSIUS
1
HOUR
Heat a solution of 6′-chloro-3-trifluoromethyl-[2,3′]bipyridinyl-5′-ylamine (25 g, 0.091 mol), zinc cyanide (6.75 g, 0.058 mol), tris[dibenzylidineacetone]di-palladium (pd2(dba)3; 2.63 g, 2.86 mmol), and 1,1′-bis(diphenylphosphino)ferrocene (DPPF; 3.16 g, 5.72 mmol) in DMF (250 mL) and water (2.5 mL), under a nitrogen ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Tertiary amide
Primary amide
c1ccncc1
c1ccncc1
c1ccncc1.c1ccncc1
HCl
[C-]#N.[Zn+2].[C-]#N.C1(=CC=CC=C1)P([C-]1C=CC=C1)C1=CC=CC=C1.[C-]1(C=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Fe+2].O
0
1
CN(C)C=O.Nc1cc(-c2ncccc2C(F)(F)F)cnc1Cl.[NH4+]>[C-]#N.[Zn+2].[C-]#N.C1(=CC=CC=C1)P([C-]1C=CC=C1)C1=CC=CC=C1.[C-]1(C=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[Fe+2].O>NC(=O)c1ncc(-c2ncccc2C(F)(F)F)cc1N