Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → N-(4-Bromo-phenyl)-2-(2-chloro-5-{[(1,1-difluoro-ethylcarbonyl)-amino]-methyl}-phenylamino)-6-(2,2-difluoro-ethoxy)-1-methyl-1H-benzimidazole-5-carboxylic acid amide

HRID 1410247Notes

Reaction equation

HRID 1410247 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[C:30]([O:31][CH2:32][CH:33]([F:35])[F:34])=[CH:29][C:14]3[N:15]([CH3:28])[C:16]([NH:18][C:19]4[CH:24]=[C:23]([CH2:25][NH2:26])[CH:22]=[CH:21][C:20]=4[Cl:27])=[N:17][C:13]=3[CH:12]=2)=[O:10])=[CH:4][CH:3]=1.[F:36][C:37]([F:42])([CH3:41])[C:38](O)=[O:39].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[C:30]([O:31][CH2:32][CH:33]([F:35])[F:34])=[CH:29][C:14]3[N:15]([CH3:28])[C:16]([NH:18][C:19]4[CH:24]=[C:23]([CH2:25][NH:26][C:38]([C:37]([F:42])([F:36])[CH3:41])=[O:39])[CH:22]=[CH:21][C:20]=4[Cl:27])=[N:17][C:13]=3[CH:12]=2)=[O:10])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27828252,2-Difluoropropionic acidHCID 59529876N-(4-bromo-phenyl)-2-(2-chloro-5-{[amino]-methyl}-phenylamino)-6-(2,2-difluoro-ethoxy)-1-methyl-1H-benzimidazole-5-carboxylic acid amide

Product 1

HCID 46908544N-(4-Bromo-phenyl)-2-(2-chloro-5-{[(1,1-difluoro-ethylcarbonyl)-amino]-methyl}-phenylamino)-6-(2,2-difluoro-ethoxy)-1-methyl-1H-benzimidazole-5-carboxylic acid amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The title compound was prepared in accordance with Example 72, step (c) using N-(4-bromo-phenyl)-2-(2-chloro-5-{[amino]-methyl}-phenylamino)-6-(2,2-difluoro-ethoxy)-1-methyl-1H-benzimidazole-5-carboxylic acid amide (170 mg; 0.30 mmol), 2,2-difluoropropanoic acid (33 mg; 0.30 mmol), HBTU (114 mg; 0.30 mmol), TEA (61 mg; 0.60 mmol) and DMF (3 mL). Yield: 63 mg (32%). 400 MHz 1H-NMR (DMSO-d6, ppm) 10.07 (1H, s) 9.30 (1H, t, J=5.8 Hz) 8.35 (1H, s) 7.87-7.82 (1H, m) 7.73-7.60 (3H, m) 7.53-7.39 (3H, m) 7.33-7.27 (1H, m) 6.99-6.90 (1H, m) 6.66-6.34 (1H, m) 4.59-4.44 (2H, m) 4.30 (2H, d, J=5.8 Hz) 3.71 (2.38H, s, major tautomer) 3.43 (0.41H, s, minor tautomer) 1.74 (3H, t, J=19.6 Hz). MS m/z: 656, 658, 660 [M+H]+.

Sources & evidence

ORD record
ord-f92f8b373d3c4410a296dbc0675026c6
Source dataset
uspto-grants-2014_12
Patent number
US08921405B2

Reaction notes

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