Diisopropylcarbodiimide → 2-(2-chloro-5-{[(1-trifluoromethyl-cyclopropanecarbonyl)-amino]-methyl}-phenylamino)-6-methoxy-1-methyl-1H-benzimidazole-5-carboxylic acid

HRID 1410221Notes

Reaction equation

HRID 1410221 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][NH:7][C:8]([C:10]2([C:13]([F:16])([F:15])[F:14])[CH2:12][CH2:11]2)=[O:9])=[CH:4][C:3]=1[N:19]=[C:20]=S.[NH2:22][C:23]1[C:24]([NH:34][CH3:35])=[CH:25][C:26]([O:32][CH3:33])=[C:27]([CH:31]=1)[C:28]([OH:30])=[O:29].FC(F)(F)C(=N[Si](C)(C)C)O[Si](C)(C)C.CC(C)N=C=NC(C)C>CN(C=O)C.C(O)(=O)C>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][NH:7][C:8]([C:10]2([C:13]([F:16])([F:15])[F:14])[CH2:12][CH2:11]2)=[O:9])=[CH:4][C:3]=1[NH:19][C:20]1[N:34]([CH3:35])[C:24]2[CH:25]=[C:26]([O:32][CH3:33])[C:27]([C:28]([OH:30])=[O:29])=[CH:31][C:23]=2[N:22]=1

Participants

7

Reactant 4

HCID 12734DiisopropylcarbodiimideHCID 94358Bis(trimethylsilyl)trifluoroacetamideHCID 595298385-Amino-2-methoxy-4-(methylamino)benzoic acidHCID 86646336N-(4-Chloro-3-isothiocyanatobenzyl)-1-(trifluoromethyl)cyclopropane carboxamide

Product 1

HCID 595298032-(2-chloro-5-{[(1-trifluoromethyl-cyclopropanecarbonyl)-amino]-methyl}-phenylamino)-6-methoxy-1-methyl-1H-benzimidazole-5-carboxylic acid

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of N-(4-chloro-3-isothiocyanatobenzyl)-1-(trifluoromethyl)cyclopropane carboxamide (1.71 g; 5.10 mmol) and 5-amino-2-methoxy-4-(methylamino)benzoic acid (1.00 g; 1.00 mmol) in DMF (20 mL) was stirred over night at rt. The mixture was thereafter heated to 60° C. and BSTFA (1.44 g; 5.61 mmol) was added and stirred for 1 h before the addition of DIC (0.772 g; 6.12 mmol). The resulting mixture was stirred at 80° C. for 3 h. Acetic acid (2 mL) was added and the mixture was concentrated and the residue poured in aqueous NaOH (2 M) and pH adjusted to −3-4. The mixture was extracted with EtOAc and the organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was recrystallized from EtOAc/petroleum ether to give the sub-title compound. Yield: 0.570 g (22%).

Workup

  1. temperatureThe mixture was thereafter heated to 60° C.
  2. stirringThe resulting mixture was stirred at 80° C. for 3 h
  3. concentrationthe mixture was concentrated
  4. additionthe residue poured in aqueous NaOH (2 M)
  5. extractionThe mixture was extracted with EtOAc
  6. washthe organic extracts were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was recrystallized from EtOAc/petroleum ether

Sources & evidence

ORD record
ord-19dd33d443ba40c4a428892582770567
Source dataset
uspto-grants-2014_12
Patent number
US08921405B2

Reaction notes

Loading…