Methyl chloroformate → (R)-methyl 4-(2-fluoro-3-(3-(2-methylpyridin-4-yl)ureido)benzyl)-2-methylpiperazine-1-carboxylate

Participants

Reaction Steps

To a solution of (R)-benzyl 4-(2-fluoro-3-(3-(6-methylpyridin-4-yl)ureido)benzyl)-2-methylpiperazine-1-carboxylate (190 mg, 0.39 mmol, 1.0 equiv) in MeOH (20 mL) was added 10% Pd/C (approx. 100 mg). The resulting suspension was stirred and sparged with hydrogen gas using a balloon and needle. After 1 h, reaction was complete, as determined by LCMS. The mixture was filtered through a pad of Celite, and the celite pad was washed with additional methanol. The mixture was concentrated in vacuo, and the resulting residue was dissolved in dry DCM (10 mL). To this room temperature solution was added Et3N (167 uL, 1.2 mmol, 3.0 equiv), followed by the addition of methyl chloroformate (46 uL, 0.60 mmol, 1.5 equiv) by syringe. After 10 minutes the reaction mixture was quenched by the addition of methanol. The solvent was removed in vacuo, and the mixture was purified by preparative TLC (0.5% Et3N/7% MeOH/92.5% DCM) to provide (R)-methyl 4-(2-fluoro-3-(3-(2-methylpyridin-4-yl)ureido)benzyl)-2-methylpiperazine-1-carboxylate (85.9 mg, 50%). LCMS m/z (APCI)=416.3 (M+H).

Provenance & Evidence