Sodium hydride → HCID 178463586, compound

Participants

Reaction Steps

tert-Butyl 9-trityl-9H-purin-6-ylcarbamate (102 mg, 0.213 mmol) was added to a solution of 50% dispersion in mineral oil NaH (5.12 mg, 0.213 mmol) in N,N-dimethylformamide (0.5 ml) and the mixture was stirred at RT for 30 min. 3-(1-Bromoethyl)-4-(5-(morpholinomethyl)thiophen-2-yl)-1H-isochromen-1-one hydrobromide (intermediate C16, 100 mg, 0.194 mmol) was suspended in DMF (0.5 ml, 0.194 mmol) and reacted with 50% dispersion in mineral oil NaH (5.1 mg, 0.213 mmol) at RT for 15 min. The resulting solution was added to the previous prepared mixture and left on stirring at 60° C. for 1 hrs, at RT for 3 hrs and then at 80° C. for 3 hrs. The reaction mixture was poured into brine and extracted with EtOAc. The collected organic phases were dried and concentrated. The resulting crude material was purified under reverse phase chromatography using a Biotage C18 60 g SNAP cartridge. The collected fractions were added with 37% HClaqueous (1 ml) and concentrated. The resulting material was further purified under reverse phase chromatography using a Biotage C18 30 g SNAP cartridge. The resulting material was finally purified on silica with a gradient of DCM and 2-propanol, modified with 0.5% TEA, to give the title compound (9 mg, 9.5%).

Provenance & Evidence