4-Methylmorpholine → HCID 178454216, compound

Participants

Reaction Steps

To a solution of Boc-Asn(Trt)-OH (100.4 mg, 0.2116 mmol) in acetonitrile (2.0 mL) cooled in an ice water bath was added 4-methylmorpholine (0.059 mL, 0.53 mmol) and isobutyl chloroformate (0.027 mL, 0.21 mmol). After stirring for 60 minutes, 3′,4′-diamino-3-fluoro-[1,1-biphenyl]-4-carbonitrile (Preparation 81, 42.7 mg, 0.188 mmol) was added and the mixture allowed to warm to room temperature. After stirring for 18 hours the reaction mixture was concentrated in vacuo and redissolved in acetic acid. After stirring at room temperature for 6.5 hours, the mixture was concentrated in vacuo, redissolved in ethyl acetate, washed with water, 0.5M HCl, and brine. The organic layer was dried over anhydrous magnesium sulphate, filtered, and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with a 0-100% ethyl acetate/hexanes gradient to afford the title compound (75 mg, 60%).

Provenance & Evidence