Diisopropylcarbodiimide → N-(4-Bromo-phenyl)-2-(2-trifluoromethyl-5-{[(1-trifluoromethyl-cyclopropanecarbonyl)-amino]-methyl}-phenylamino)-6-(2,2-difluoro-ethoxy)-1-methyl-1H-benzimidazole-5-carboxylic acid amide

HRID 1410253Notes

Reaction equation

HRID 1410253 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[CH:19]=[CH:18][C:6]([CH2:7][NH:8][C:9]([C:11]2([C:14]([F:17])([F:16])[F:15])[CH2:13][CH2:12]2)=[O:10])=[CH:5][C:4]=1[N:20]=[C:21]=S.[NH2:25][C:26]1[C:27]([NH:47][CH3:48])=[CH:28][C:29]([O:42][CH2:43][CH:44]([F:46])[F:45])=[C:30]([CH:41]=1)[C:31]([NH:33][C:34]1[CH:39]=[CH:38][C:37]([Br:40])=[CH:36][CH:35]=1)=[O:32].CC(C)N=C=NC(C)C>CN(C=O)C>[Br:40][C:37]1[CH:38]=[CH:39][C:34]([NH:33][C:31]([C:30]2[C:29]([O:42][CH2:43][CH:44]([F:45])[F:46])=[CH:28][C:27]3[N:47]([CH3:48])[C:21]([NH:20][C:4]4[CH:5]=[C:6]([CH2:7][NH:8][C:9]([C:11]5([C:14]([F:17])([F:16])[F:15])[CH2:13][CH2:12]5)=[O:10])[CH:18]=[CH:19][C:3]=4[C:2]([F:24])([F:23])[F:1])=[N:25][C:26]=3[CH:41]=2)=[O:32])=[CH:35][CH:36]=1

Participants

5

Reactant 3

HCID 12734DiisopropylcarbodiimideHCID 595298615-amino-N-(4-bromophenyl)-2-(2,2-difluoroethoxy)-4-(methylamino)benzamideHCID 86646341N-(4-trifluoromethyl-3-isothiocyanato-benzyl)-1-(trifluoromethyl)cyclopropane carboxamide

Product 1

HCID 46908831N-(4-Bromo-phenyl)-2-(2-trifluoromethyl-5-{[(1-trifluoromethyl-cyclopropanecarbonyl)-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 the procedure in Example 72, step (a) using N-(4-trifluoromethyl-3-isothiocyanato-benzyl)-1-(trifluoromethyl)cyclopropane carboxamide (184 mg; 0.50 mmol), 5-amino-N-(4-bromophenyl)-2-(2,2-difluoroethoxy)-4-(methylamino)benzamide (200 mg; 0.50 mmol), DIC (63 mg; 0.50 mmol) and DMF (4 mL). Yield: 59 mg (16%). 400 MHz 1H-NMR (DMSO-d6, ppm) 10.62 (0.57H, s, major tautomer) 10.09-9.96 (1H, m) 8.47-8.41 (0.38H, m, minor tautomer) 8.36-8.28 (1H, m) 7.72-7.61 (3H, m) 7.58-7.47 (3H, m) 7.36-7.28 (1H, m) 7.12-6.84 (2H, m) 6.67-6.35 (1H, m) 4.58-4.45 (2H, m) 4.34-4.25 (2H, m) 3.64 (0.96H, s, minor tautomer) 3.41 (1.93H, s, major tautomer) 1.31-1.17 (4H, m). MS m/z: 734, 736 [M+H]+.

Sources & evidence

ORD record
ord-fdc37406e76d41d89739cd9e3f3b843a
Source dataset
uspto-grants-2014_12
Patent number
US08921405B2

Reaction notes

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