Dimethylformamide → HCID 131735865, compound

Participants

Reaction Conditions

Reaction Steps

In a 15 mL pressure tube, 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoic acid (prepared as described in US20100152190A1, 100 mg, 162 μmol), 2-chloro-1-(4-methylpiperazin-1-yl)ethanone, hydrochloride (34.6 mg, 162 μmol) and cesium carbonate (111 mg, 341 μmol) were combined with dry dimethyl formamide (2 mL) to give a white suspension. The tube was capped and heated at 50° C. with stirring. After 1.5 h, the reaction mixture was cooled down to room temperature. It was poured into water and extracted with methylene chloride (2×). The methylene chloride layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography (24 g pre-packed silica gel column, eluted with methanol in methylene chloride) to give 4-{[(2R,3S,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid 2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl ester, hydrochloride as an off-white solid (99 mg, 81% yield). The product was mixed with acetonitrile (2 mL) to form a suspension. A few drops of 1N aqueous hydrochloric acid were added to the mixture. The suspension became clear solution. It was frozen and lyophilized to give an off-white solid as hydrochloride salt. LCMS (ES+) m/z calcd. for C38H42Cl2F2N5O5 [(M+H)+]: 756. found: 756.

Provenance & Evidence