反应详情

A brown solution of 8-bromo-2-chloro-7-fluoro-3-methylquinazolin-4(3H)-one (720, 180 mg, 0.617 mmol), 1-methylcyclopropanamine hydrochloride (Small Molecules, Inc., 133 mg, 1.235 mmol), and N-ethyl-N-isopropylpropan-2-amine (237 μL, 1.358 mmol) in DMSO (6.2 mL) was stirred at 80° C. for 1 h when product was observed via LCMS. The reaction mixture was diluted with EtOAc (100 mL), added to a separatory funnel, and washed with saturated aqueous NaHCO3 (2×75 mL); the organic layer was separated, dried over Na2SO4, and concentrated. The crude product was adsorbed onto silica and was purified via automated flash chromatography (silica gel) with 0-100% EtOAc in hexanes to give 8-bromo-7-fluoro-3-methyl-2-((1-methylcyclopropyl)amino)quinazolin-4(3H)-one (510a, 88 mg, 0.270 mmol, 43% yield) as a brown oil. 1H NMR (400 MHz, CDCl3) δ ppm 0.80-0.87 (m, 2H) 0.87-0.93 (m, 2H) 1.61 (s, 3H) 3.42 (s, 3H) 5.12 (br. s., 1H) 6.92 (t, J=8.51 Hz, 1H) 8.06 (dd, J=8.80, 6.06 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ ppm −96.48 (s, 1F). MS (ESI, pos. ion) m/z: 326.0/328.0 (M+1).

1. additionadded to a separatory funnel
2. washwashed with saturated aqueous NaHCO3 (2×75 mL)
3. customthe organic layer was separated
4. dry with materialdried over Na2SO4
5. concentrationconcentrated
6. customwas purified