Diisopropylethylamine → 8-bromo-7-fluoro-3-methyl-2-((1-methylcyclobutyl)amino)-quinazolin-4(3H)-one

Participants

Reaction Steps

A solution of 8-bromo-2-chloro-7-fluoro-3-methylquinazolin-4(3H)-one (720, 239 mg, 0.820 mmol), 1-methylcyclobutanamine hydrochloride (Oakwood Products, Inc., West Columbia, S.C., 199 mg, 1.640 mmol), and N-ethyl-N-isopropylpropan-2-amine (314 μL, 1.804 mmol) in DMSO (8.2 mL) was stirred at 80° C. for 1 h. The reaction mixture was diluted with EtOAc (100 mL), added to a separatory funnel, and washed with saturated aqueous NaHCO3 (3×100 mL); the organic layer was separated, dried over Na2SO4, and concentrated. The crude product was loaded onto the column and was purified via automated flash chromatography (silica gel) with 0-40% EtOAc in hexanes to give 8-bromo-7-fluoro-3-methyl-2-((1-methylcyclobutyl)amino)quinazolin-4(3H)-one (502a, 0.120 g, 0.353 mmol, 43% yield) as a brown amorphous solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.74 (s, 3H) 1.89-2.00 (m, 2H) 2.26-2.36 (m, 2H) 2.38-2.49 (m, 2H) 3.46 (s, 3H) 4.72 (br. s., 1H) 6.90 (t, J=8.51 Hz, 1H) 8.06 (dd, J=8.80, 6.06 Hz, 1H). 19F NMR (377 MHz, CDCl3) δ ppm −96.60 (s, 1F). MS (ESI, pos. ion) m/z: 340.0/341.9 (M+1).

Provenance & Evidence