Diisopropylcarbodiimide → Ethyl-2-(2-chloro-5-{[(tert-butoxycarbonyl)-amino]-methyl}-phenylamino)-6-(2,2-difluoro-ethoxy)-1-methyl-1H-benzimidazole-5-carboxylate

HRID 1410243Notes

Reaction equation

HRID 1410243 reaction equation
[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[CH:4][C:3]=1[N:17]=[C:18]=S.[NH2:20][C:21]1[C:22]([NH:37][CH3:38])=[CH:23][C:24]([O:32][CH2:33][CH:34]([F:36])[F:35])=[C:25]([CH:31]=1)[C:26]([O:28][CH2:29][CH3:30])=[O:27].CC(C)N=C=NC(C)C>CN(C=O)C>[CH2:29]([O:28][C:26]([C:25]1[C:24]([O:32][CH2:33][CH:34]([F:35])[F:36])=[CH:23][C:22]2[N:37]([CH3:38])[C:18]([NH:17][C:3]3[CH:4]=[C:5]([CH2:6][NH:7][C:8]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:14])[CH:15]=[CH:16][C:2]=3[Cl:1])=[N:20][C:21]=2[CH:31]=1)=[O:27])[CH3:30]

Participants

5

Reactant 3

HCID 12734DiisopropylcarbodiimideHCID 59529827Ethyl 2-(2,2-difluoroethoxy)-4-methylamino-5-amino-benzoateHCID 86646335tert-Butyl 4-chloro-3-isothiocyanatobenzylcarbamate

Product 1

HCID 86646338Ethyl-2-(2-chloro-5-{[(tert-butoxycarbonyl)-amino]-methyl}-phenylamino)-6-(2,2-difluoro-ethoxy)-1-methyl-1H-benzimidazole-5-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of tert-butyl 4-chloro-3-isothiocyanatobenzylcarbamate ((see Example 2, step (c)) 974 mg; 3.26 mmol) and ethyl 5-amino-2-(2,2-difluoroethoxy)-4-(methylamino)benzoate ((see Example 59, step (g)) 894 mg; 3.26 mmol) in DMF (10 mL) was stirred over night at rt. DIC (411 mg; 3.26 mmol) was added and the mixture was heated at 90° C. for 1.5 h. The mixture was concentrated and the residue was recrystallized from EtOAc/petroleum ether and washed with Et2O to give the sub-title compound. Yield: 1.75 g (99%).

Workup

  1. temperaturethe mixture was heated at 90° C. for 1.5 h
  2. concentrationThe mixture was concentrated
  3. customthe residue was recrystallized from EtOAc/petroleum ether
  4. washwashed with Et2O

Sources & evidence

ORD record
ord-d95017ae52904465b5be17bdf8f2a29f
Source dataset
uspto-grants-2014_12
Patent number
US08921405B2

Reaction notes

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