Diisopropylethylamine → N-(3-Chloro-4-fluoro-phenyl)-2-{2,6-dichloro-3-[(2-fluoro-2-methyl-propionylamino)-methyl]-phenylamino}-6-(2,2-difluoroethoxy)-1-methyl-1H-benzimidazole-5-carboxylic acid amide

HRID 410121Notes

Reaction equation

HRID 410121 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[Cl:23][C:24]1[CH:25]=[C:26]([NH:31][C:32]([C:34]2[C:54]([O:55][CH2:56][CH:57]([F:59])[F:58])=[CH:53][C:37]3[N:38]([CH3:52])[C:39]([NH:41][C:42]4[C:47]([Cl:48])=[CH:46][CH:45]=[C:44]([CH2:49][NH2:50])[C:43]=4[Cl:51])=[N:40][C:36]=3[CH:35]=2)=[O:33])[CH:27]=[CH:28][C:29]=1[F:30].CCN(C(C)C)C(C)C.[F:69][C:70]([CH3:75])([CH3:74])[C:71](O)=[O:72]>CN(C=O)C>[Cl:23][C:24]1[CH:25]=[C:26]([NH:31][C:32]([C:34]2[C:54]([O:55][CH2:56][CH:57]([F:58])[F:59])=[CH:53][C:37]3[N:38]([CH3:52])[C:39]([NH:41][C:42]4[C:47]([Cl:48])=[CH:46][CH:45]=[C:44]([CH2:49][NH:50][C:71](=[O:72])[C:70]([F:69])([CH3:75])[CH3:74])[C:43]=4[Cl:51])=[N:40][C:36]=3[CH:35]=2)=[O:33])[CH:27]=[CH:28][C:29]=1[F:30]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27828282-Fluoro-2-methylpropanoic acidHCID 86669639N-(3-Chloro-4-fluoro-phenyl)-2-(2,6-dichloro-3-aminomethyl-phenylamino)-6-(2,2-difluoroethoxy)-1-methyl-1H-benzimidazole-5-carboxylic acid amide

Product 1

HCID 86669640N-(3-Chloro-4-fluoro-phenyl)-2-{2,6-dichloro-3-[(2-fluoro-2-methyl-propionylamino)-methyl]-phenylamino}-6-(2,2-difluoroethoxy)-1-methyl-1H-benzimidazole-5-carboxylic acid amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

TBTU (1.0 mL of a 0.11 M solution in DMF) was added to a mixture of N-(3-chloro-4-fluoro-phenyl)-2-(2,6-dichloro-3-aminomethyl-phenylamino)-6-(2,2-difluoroethoxy)-1-methyl-1H-benzimidazole-5-carboxylic acid amide (1.0 mL of a 0.10 M solution in DMF), DIPEA (52 μl, 0.3 mmol) and 2-fluoro-2-methylpropionic acid (1.0 mL of a 0.13 M solution in DMF) and it was stirred for 3 d and the mixture was purified by prep. HPLC.

Workup

  1. customthe mixture was purified by prep

Sources & evidence

ORD record
ord-1ebd60b54b654ef98fd4eca3d1eb8ddb
Source dataset
uspto-grants-2014_06
Patent number
US08759537B2

Reaction notes

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