Potassium Carbonate → 9-benzyloxy-6-(5-chloro-4'-fluoro-biphenyl-2-ylmethyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

Participants

Reaction Conditions

Reaction Steps

Into a sealed tube was placed a stirred solution of 9-benzyloxy-6-(2-bromo-4-chlorobenzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (380) (70 mg, 0.136 mmol) in dioxane (3 mL). 4-Fluorophenyl boronic acid (18.99 mg, 0.14 mmol) and a 1N solution of potassium carbonate [(56.244 mg, 0.407 mmol) in 0.82 mL water] were added at room temperature and the reaction mixture was purged for 30 min with argon. To the reaction Pd(triphenyl phosphine)4 (15.676 mg, 0.014 mmol) was added under argon, followed by 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (11.138 mg, 0.027 mmol). The reaction mixture was further degassed for another 10 min, then heated to 80° C. for 30 min (monitored by LC-MS). The reaction mixture was filtered through a pad of celite. The filtrate was diluted with water (5 mL) and extracted with ethyl acetate (2×20 mL). The combined extracts were dried and concentrated. The resulting crude product was purified by column chromatography (using amine bound silica gel) to get 9-benzyloxy-6-(5-chloro-4′-fluoro-biphenyl-2-ylmethyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (385) (32 mg, 44.34%) as an off-white solid.

Provenance & Evidence