Dimethylamine → N-(4-Fluorobenzyl)-3-hydroxy-10-(methyl((5-methyl-3-isoxazolyl)carbonyl)amino)-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxamide

Participants

Reaction Steps

To a solution of N-(4-fluorobenzyl)-3-hydroxy-10-(methylamino)-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxamide (25 mg, 0.061 mmol) in CH2Cl2 (2 mL) was added triethylamine (0.051 mL, 0.365 mmol) followed by 5-methylisoxazole-3-carbonyl chloride (17.69 mg, 0.122 mmol) and the resulting mixture was stirred at room temperature. After 16 at room temperature the reaction mixture was concentrated to give crude product which was dissolved in methanol (2 mL) and treated with 2M dimethylamine in methanol (0.5 mL). The resulting reaction mixture was stirred at 60° C. for 2 h, then cooled and purified by preparative HPLC to afford the title compound (5 mg, 17% yield) as an off-white solid. 1H NMR (500 MHz, CDCl3) δ: 11.81 (1 H, brs), 8.70 (1 H, d, J=5.19 Hz), 7.31 (2 H, dd, J=8.55, 5.49 Hz), 6.92-7.01 (2 H, m), 6.09 (1 H, s), 4.75-4.86 (1 H, m), 4.58-4.67 (1 H, m), 4.38-4.47 (1 H, m), 3.67 (1 H, d, J=15.56 Hz), 3.35-3.46 (1 H, m), 3.13 (3 H, s), 2.50 (1 H, brs), 2.41 (3 H, s), 2.07-2.16 (3 H, m), 1.95-2.05 (1 H, m), 1.72-1.86 (2 H, m), 1.37-1.50 (1 H, m). LCMS (M+H)=496.66. HPLC purity: >95%.

Provenance & Evidence