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

Participants

Reaction Conditions

Reaction Steps

In 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) (80 mg, 0.155 mmol) in dioxane (3 mL). 4-Chlorophenyl boronic acid (24.248 mg, 0.155 mmol) and a 1N solution of K2CO3 [(64.279 mg, 0.465 mmol) dissolved in 0.7 mL water] were added at room temperature and the reaction was degassed for 30 min under argon. To the reaction mixture, Pd(triphenyl phosphine)4 (17.916 mg, 0.016 mmol) was added, followed by 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (12.729 mg, 0.031 mmol) and the reaction was further degassed for another 10 min. The reaction mixture was heated at 80° C. for 20 min (reaction was monitored by LC-MS). After completion of the reaction, the mixture was filtered and the filtrate was diluted with water (5 mL). After extraction with ethyl acetate (2×20 mL), the organic part was dried over sodium sulphate and concentrated. The resulting crude product was purified by column chromatography (using amine bound silica gel as stationary phase) to get 9-benzyloxy-6-(5,4′-dichloro-biphenyl-2-ylmethyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (381) (42 mg, 49.39%) as a white solid.

Provenance & Evidence