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

HRID 1410218Notes

Reaction equation

HRID 1410218 reaction equation
[NH2:1][C:2]1[C:3]([NH:18][CH3:19])=[CH:4][C:5]([O:13][CH2:14][CH:15]([F:17])[F:16])=[C:6]([CH:12]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8].[Cl:20][C:21]1[CH:37]=[CH:36][C:24]([CH2:25][NH:26][C:27]([C:29]2([C:32]([F:35])([F:34])[F:33])[CH2:31][CH2:30]2)=[O:28])=[CH:23][C:22]=1[N:38]=[C:39]=S.CC(C)N=C=NC(C)C>C1COCC1>[Cl:20][C:21]1[CH:37]=[CH:36][C:24]([CH2:25][NH:26][C:27]([C:29]2([C:32]([F:35])([F:34])[F:33])[CH2:31][CH2:30]2)=[O:28])=[CH:23][C:22]=1[NH:38][C:39]1[N:18]([CH3:19])[C:3]2[CH:4]=[C:5]([O:13][CH2:14][CH:15]([F:16])[F:17])[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:12][C:2]=2[N:1]=1

Participants

5

Reactant 3

HCID 12734Diisopropylcarbodiimide2×HCID 59529827Ethyl 2-(2,2-difluoroethoxy)-4-methylamino-5-amino-benzoate2×HCID 86646336N-(4-Chloro-3-isothiocyanatobenzyl)-1-(trifluoromethyl)cyclopropane carboxamide

Product 1

HCID 59529805Ethyl 2-(2-chloro-5-{[(1-trifluoromethyl-cyclopropanecarbonyl)-amino]-methyl}-phenylamino)-6-(2,2-difluoro-ethoxy)-1-methyl-1H-benzimidazole-5-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of ethyl 5-amino-2-(2,2-difluoroethoxy)-4-(methylamino)benzoate (0.737 g; 2.68 mmol; crude material from step (g)) and N-(4-chloro-3-isothiocyanatobenzyl)-1-(trifluoromethyl)cyclopropane carboxamide (0.900 g; 2.68 mmol) in THF (100 mL) was stirred over night at rt. DIC (0.338 g; 2.68 mmol) was added and the mixture was stirred for 6 h at rt. Another portion of DIC (0.169 g; 1.34 mmol) was added and the mixture stirred for another 6 h at rt. The mixture was concentrated and purified by column chromatography to give the sub-title compound. Yield: 0.790 g (51%).

Workup

  1. stirringthe mixture was stirred for 6 h at rt
  2. stirringthe mixture stirred for another 6 h at rt
  3. concentrationThe mixture was concentrated
  4. custompurified by column chromatography

Sources & evidence

ORD record
ord-1b94fe38a39242c29463ff37ac6c2eaa
Source dataset
uspto-grants-2014_12
Patent number
US08921405B2

Reaction notes

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