Formic Acid → HCID 136163957, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-(benzyloxy)-2-(4-chloro-5-(4-fluorobenzyl)-1H-imidazol-2-yl)-9,9-dimethyl-6,7-dihydropyrimido[2,1-c][1,4]oxazin-4(9H)-one (0.03 g, 0.061 mmol, 1.0 equiv) in MeOH (3 mL) under a nitrogen atmosphere, was added formic acid (0.1 mL, 2.61 mmol, 43 equiv) and 10% Pd/C (0.065 g, 0.061 mmol, 1.0 equiv). The reaction was stirred for 5 h after which LCMS analysis indicated complete benzyl hydrogenolysis but no chloride reduction. The reaction was warmed to 40° C. (oil bath) and stirred 2 h. LCMS analysis now indicated complete chloride reduction. The reaction was cooled to ambient temperature and stirred a further 16 h. The reaction was then filtered through celite and concentrated in vacuo. The residue was added to saturated aqueous solution of NaHCO3 and extracted with CH2Cl2 (×5). The combined CH2Cl2 extracts were dried (Na2SO4) and then concentrated in vacuo. The crude product was purified by silica gel chromatography (7% MeOH/CH2Cl2) to provide the title compound (0.008 g, 36% yield) as a tan solid. 1H NMR (400 MHz, d7-DMF) δ ppm (major imidazole tautomer) 13.14 (s, 1H), 7.48-7.58 (m, 2H), 7.39 (s, 1H), 7.29 (t, J=8.56 Hz, 2H), 4.21-4.25 (m, 2H), 4.15 (s, 2H), 4.08 (t, J=5.16 Hz, 2H), 1.74 (s, 6H); LCMS (ES+, (M+H)+) m/z 371.17.

Provenance & Evidence