4-Bromoaniline → N-(4-Bromo-phenyl)-2-(2-chloro-5-{[(tert-butoxycarbonyl)-amino]-methyl}-phenylamino)-6-(2,2-difluoro-ethoxy)-1-methyl-1H-benzimidazole-5-carboxylic acid amide

HRID 1410245Notes

Reaction equation

HRID 1410245 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[CH:4][C:3]=1[NH:17][C:18]1[N:22]([CH3:23])[C:21]2[CH:24]=[C:25]([O:31][CH2:32][CH:33]([F:35])[F:34])[C:26]([C:28](O)=[O:29])=[CH:27][C:20]=2[N:19]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Br:60][C:61]1[CH:67]=[CH:66][C:64]([NH2:65])=[CH:63][CH:62]=1>CN(C=O)C.[Cl-].[Na+].O>[Br:60][C:61]1[CH:67]=[CH:66][C:64]([NH:65][C:28]([C:26]2[C:25]([O:31][CH2:32][CH:33]([F:34])[F:35])=[CH:24][C:21]3[N:22]([CH3:23])[C:18]([NH:17][C:3]4[CH:4]=[C:5]([CH2:8][NH:9][C:10]([O:12][C:13]([CH3:14])([CH3:16])[CH3:15])=[O:11])[CH:6]=[CH:7][C:2]=4[Cl:1])=[N:19][C:20]=3[CH:27]=2)=[O:29])=[CH:63][CH:62]=1

Participants

6

Reactant 3

HCID 78074-BromoanilineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 866463402-(2-chloro-5-{[(tert-butoxycarbonyl)-amino]-methyl}-phenylamino)-6-(2,2-difluoro-ethoxy)-1-methyl-1H-benzimidazole-5-carboxylic acid

Product 1

HCID 86646339N-(4-Bromo-phenyl)-2-(2-chloro-5-{[(tert-butoxycarbonyl)-amino]-methyl}-phenylamino)-6-(2,2-difluoro-ethoxy)-1-methyl-1H-benzimidazole-5-carboxylic acid amide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

A mixture of 2-(2-chloro-5-{[(tert-butoxycarbonyl)-amino]-methyl}-phenylamino)-6-(2,2-difluoro-ethoxy)-1-methyl-1H-benzimidazole-5-carboxylic acid (1.12 g; 2.19 mmol), HBTU (831 mg; 2.19 mmol) and TEA (433 mg; 4.38 mmol) in DMF (10 mL) was stirred for 30 min at rt and thereafter added to a solution of 4-bromoaniline (377 mg; 2.19 mmol) in DMF (10 mL). The resulting mixture was stirred over night at rt, poured into brine and extracted with EtOAc. The organic extracts were dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give the sub-title compound. Yield: 1.35 g (93%).

Workup

  1. stirringThe resulting mixture was stirred over night at rt
  2. extractionextracted with EtOAc
  3. dry with materialThe organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-30c7fdd20980419ba1ceb34e236d8cad
Source dataset
uspto-grants-2014_12
Patent number
US08921405B2

Reaction notes

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