Methyl chloroformate → HCID 178502277, compound

Participants

Reaction Steps

A solution of (S)—N1-(4-(4-bromo-2-(1-methylcyclopropyl)-1H-imidazol-5-yl)pyrimidin-2-yl)propane-1,2-diamine (2.02 g, 5.8 mmol) in THF-water (1:1, 60 mL) was cooled to 0° C. and then solid NaHCO3 (2.5 g, 30 mmol) was added with concomitant frothing. After 5 minutes a THF solution of methyl chloroformate (0.35 mL, 0.44 g, 4.60 mmol, freshly prepared 1.0 M solution) was added dropwise to the mixture. After 20 minutes, LCMS indicated only ˜70% conversion. Additional methylchloroformate solution (0.3 M in THF, 5 mL, 1.5 mmol) was added over 5 minutes. The reaction was maintained overnight, allowing the cooling bath to expire. LCMS indicated ˜90% conversion and additional methylchloroformate solution (0.3 M in THF, 5 mL, 1.5 mmol) at 0° C. over 5 minutes. After stirring at room temperature for 1 hour, LCMS indicated complete reaction. The reaction mixture was extracted with EtOAc. The organic phase was washed with brine and dried (Na2SO4), and concentrated to give (S)-methyl 1-(4-(4-bromo-2-(1-methylcyclopropyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate as a yellow solid (1.65 g): LCMS (m/z) 409.1 (MH+), tR=0.62 minute.

Provenance & Evidence