Methyl iodide → N-(4-Fluoro-2-(1-methyl-1H-pyrazol-3-yl)benzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide

Participants

Reaction Conditions

Reaction Steps

A solution of N-(4-fluoro-2-(1H-pyrazol-5-yl)benzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide (0.185 g, 0.36 mmol) in N,N-dimethylformamide (3 ml) was treated with iodomethane (0.025 ml, 0.4 mmol) and potassium carbonate (0.076 g, 0.55 mmol) and the resulting mixture was stirred at 25° C. for 5 h. The reaction mixture was then diluted with ethyl acetate, washed with water, brine, dried over anhydrous magnesium and concentrated. Chromatography of the residue on silica gel (elution gradient of ethyl acetate in dichloromethane) gave 0.120 g (64% yield) of the title compound as a white solid. 1HNMR 400 MHz (CDCl3) δ (ppm): 1.62 (6H, s, 2×CH3), 3.84 (3H, s, NCH3), 3.95-4.05 (4H, m, 2×CH2), 4.69 (2H, d, J=6.1 Hz, NCH2), 5.21 (2H, s, OCH2), 6.49 (1H, d, J=2.2 Hz, CH), 7.01 (1H, m, aromatic), 7.24-7.3 (4H, m, aromatics), 7.40 (1H, d, J=2.2 Hz, CH), 7.42-7.45 (2H, m, aromatics), 7.64 (1H, dd, J=6.1 Hz and J=8.6 Hz, aromatic), 8.75 (1H, broad t, NH). HRMS (ESI+) calculated for C28H29FN5O4 [M+H+]: 518.2204: found: 518.2222.

Provenance & Evidence