Tetrahydrofuran → HCID 67008776, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-[2-Amino-4-(4-methyl-piperazin-1-yl)-benzoylamino]-5-(3,5-difluoro-benzenesulfonyl)-6,6-dimethyl-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-2-carboxylic acid ethyl ester (308 mg, 0.5 mmol), N,N-diisopropylethylamine (0.104 mL, 0.6 mmol, 1.2 eq), morpholine-4-carbonyl chloride (1.2 mL, 10 mmol, 20 eq) and tetrahydrofuran (20 mL) was stirred at 60° C. for 7 days. The reaction mixture was then poured into water (100 mL), extracted with dichloromethane (100 mL), dried over sodium sulfate and evaporated to dryness. The crude was purified by flash chromatography on silica gel (acetone as eluant) affording 112 mg of 5-(3,5-difluoro-benzenesulfonyl)-6,6-dimethyl-3-{4-(4-methyl-piperazin-1-yl)-2-[(morpholine-4-carbonyl)-amino]-benzoylamino}-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-2-carboxylic acid ethyl ester that was treated with 10 mL of methanol/triethylamine 8:2 and stirred at room temperature overnight. The mixture was evaporated to dryness and the residue purified by flash chromatography on silica gel using dichloromethane-methanol-30% NH4OH 96:4:0.4 as eluant, yielding the title compound as white solid (50 mg).

Provenance & Evidence