Hydrochloric Acid → 3-[9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]-N-methoxy-N-methylpentanamide

Participants

Reaction Steps

To a solution of ethyl 3-[9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]pentanoate (200 mg, 0.416 mmol) in tetrahydrofuran (10 mL) and methanol (5.0 mL) was added 1N sodium hydroxide (2.0 mL, 2.0 mmol) at room temperature. The mixture was stirred at room temperature for 3 days. To the reaction mixture was added 1N hydrogen chloride (2.0 mL, 2.0 mmol) at room temperature and the mixture was concentrated in vacuo. To the residue was added N,N-dimethylformamide (10 mL) and to the mixture were added N,O-dimethylhydroxylamine hydrochloride (81 mg, 0.83 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (159 mg, 0.83 mmol), 1-hydroxybenzotriazole monohydrate (127 mg, 0.83 mmol) and triethylamine (0.29 mL, 2.08 mmol). The mixture was stirred at room temperature for 24 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 25-75% ethyl acetate/n-hexane gradient mixture to give the title compound (148.6 mg, 0.30 mmol, 72%) as a pale yellow amorphous.

Provenance & Evidence