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

HRID 1410248Notes

Reaction equation

HRID 1410248 reaction equation
[C:1](Cl)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[Br:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]2[C:37]([O:38][CH2:39][CH:40]([F:42])[F:41])=[CH:36][C:21]3[N:22]([CH3:35])[C:23]([NH:25][C:26]4[CH:31]=[C:30]([CH2:32][NH2:33])[CH:29]=[CH:28][C:27]=4[Cl:34])=[N:24][C:20]=3[CH:19]=2)=[O:17])=[CH:11][CH:10]=1.O>C(Cl)Cl>[Br:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]2[C:37]([O:38][CH2:39][CH:40]([F:42])[F:41])=[CH:36][C:21]3[N:22]([CH3:35])[C:23]([NH:25][C:26]4[CH:31]=[C:30]([CH2:32][NH:33][C:1]([C:2]([CH3:5])([CH3:4])[CH3:3])=[O:6])[CH:29]=[CH:28][C:27]=4[Cl:34])=[N:24][C:20]=3[CH:19]=2)=[O:17])=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 962WaterHCID 62493Pivaloyl chlorideHCID 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 46908736N-(4-Bromo-phenyl)-2-(2-chloro-5-{[(tert-butylcarbonyl)-amino]-methyl}-phenylamino)-6-(2,2-difluoro-ethoxy)-1-methyl-1H-benzimidazole-5-carboxylic acid amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of pivaloyl chloride (34 mg; 0.28 mmol) in DCM (1 mL) was added dropwise to a mixture of N-(4-bromo-phenyl)-2-(2-chloro-5-{[amino]-methyl}-phenylamino)-6-(2,2-difluoro-ethoxy)-1-methyl-1H-benzimidazole-5-carboxylic acid amide ((see Example 72, step (d)) 150 mg; 0.27 mmol), TEA (41 mg; 0.41 mmol) and DCM (2 mL) at 0° C. The resulting mixture was stirred over night at rt, poured into water and extracted with DCM. The organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was recrystallized from EtOAc/petroleum ether to give the title compound.

Workup

  1. extractionextracted with DCM
  2. washThe organic extracts were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was recrystallized from EtOAc/petroleum ether

Sources & evidence

ORD record
ord-77e76243d67944838da1197ec27784a5
Source dataset
uspto-grants-2014_12
Patent number
US08921405B2

Reaction notes

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