Methyl iodide → 3-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-3-methoxypiperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Steps

To a solution of 3-[2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-3-hydroxypiperidine-1-carboxylic acid tert-butyl ester (1.0 g, 1.78 mmol) in THF (20 mL) was added NaH (86 mg, 2.14 mmol, 60% dispersion in mineral oil) and the resulting mixture allowed to stir for 5 min before the addition of iodomethane (135 μL, 2.14 mmol) and 15-Crown-5 (4 drops). The resulting mixture was stirred for 3 h before further NaH (86 mg, 2.14 mmol) and iodomethane (135 μL, 2.14 mmol) were added. The resulting mixture was allowed to stir for 8 days then partitioned between 2-methyl THF and H2O. The organic phase was washed with sat. aq. NaHCO3 and brine, then dried (Na2SO4) and concentrated in vacuo affording 3-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-3-methoxypiperidine-1-carboxylic acid tert-butyl ester. LCMS (method H): RT 3.28 min [M+H]+ 577.5

Provenance & Evidence