Methyl iodide → 2-Chloro-9-cyclohexyl-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

Participants

Reaction Steps

To a solution of compound 2-Chloro-9-cyclohexyl-7,7-difluoro-8,9-dihydro-5H-pyrimido[5,4-b][1,4]diazepin-6(7H)-one (6.0 g, 18.98 mmol) in 30 mL of DMA was added sodium hydride (60% dispersion in mineral oil, 1.138 g, 28.47 mmol) at 0° C., followed by the dropwise addition of methyl iodide (1.42 mL, 22.78 mmol). The reaction mixture was warmed up to rt and stirred for 1 h. The whole was poured into ice-water, extracted with ethyl acetate. The organic layer was washed with brine and dried over Na2SO4. The solution was concentrated in vacuo followed by precipitation from ether/EtOA to afford the desired compound (3.0 g, 47.9% yield) as white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.97-1.85 (m, 10 H) 3.33 (s, 3 H) 4.15 (t, J=12.88 Hz, 2 H) 4.44 (m, 1 H) 8.31 (s, 1 H). [M+H] calc'd for C14H17ClF2N4O, 331; found 331.

Provenance & Evidence