Water → Methyl 4-chloro-1-(3-hydroxypropyl)-2-{[6-methoxy-2-(trifluoromethyl)pyridin-3-yl]amino}-1H-benzimidazole-7-carboxylate

HRID 1398955Notes

Reaction equation

[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:12][CH2:13][CH2:14][CH2:15][OH:16])[C:3]=1[NH:17][C:18](=S)[NH:19][C:20]1[C:21]([C:28]([F:31])([F:30])[F:29])=[N:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C.O>O1CCCC1>[Cl:1][C:2]1[C:3]2[N:17]=[C:18]([NH:19][C:20]3[C:21]([C:28]([F:31])([F:30])[F:29])=[N:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=3)[N:12]([CH2:13][CH2:14][CH2:15][OH:16])[C:4]=2[C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:10][CH:11]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of methyl 4-chloro-2-[(3-hydroxypropyl)amino]-3-({[6-methoxy-2-(trifluoromethyl)pyridin-3-yl]carbamothioyl}amino)benzoate (1.85 g, 3.75 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.79 g, 4.12 mmol) and triethylamine (0.57 mL, 4.16 mmol) in tetrahydrofuran (20 mL) was stirred at 50° C. for 3 hr. Water was added to the reaction mixture at room temperature and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 25-80% ethyl acetate/n-hexane gradient mixture to give the title compound (1.50 g, 3.27 mmol, 87%) as a pale yellow solid.

Workup

extractionthe mixture was extracted with ethyl acetate
washThe organic layer was washed with water and brine
dry with materialdried over anhydrous magnesium sulfate
concentrationconcentrated in vacuo
customThe residue was purified by flash chromatography on silica gel eluting with a 25-80% ethyl acetate/n-hexane gradient mixture

Sources & evidence

ORD record: ord-a90687de23d44895aa4cfbf2146dd30a
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901141B2

Reaction notes

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