反应详情

The N-(2,5-dimorpholinopyridin-3-yl)-7-fluoro-2-(2-fluoro-5-nitrophenyl)-3-methylquinolin-4-amine (66 mg, 0.112 mmol) and methanesulfinic acid, sodium salt (12.0 mg, 0.112 mmol) was added to dimethylacetamide (0.24 mL) and placed in a microwave reactor for 2 h at 150° C. An LCMS was taken and ˜35% of starting material had converted to desired product. The mixture was reheated and stirred at 150° C. for 4 h. The reaction was then diluted with water (20 mL) and extracted with EtOAc (2×30 mL). The combined organic layers were washed with water (1×30 mL) and brine (1×30 mL) and dried over magnesium sulfate. The mixture was purified by reverse-phase preparative HPLC using a Phenomenex Gemini™ column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 90% over 20 minutes to provide N-(2,5-dimorpholinopyridin-3-yl)-7-fluoro-3-methyl-2-(2-(methylsulfonyl)-5-nitrophenyl)-quinolin-4-amine after extraction with satd sodium bicarbonate. 1H NMR (CDCl3) δ ppm 8.48-8.56 (1H, m), 8.40-8.47 (1H, m), 8.31 (1H, s), 7.88-8.04 (1H, m), 7.67 (1H, dd, J=9.5, 2.6 Hz), 7.62 (1H, d, J=2.0 Hz), 7.38-7.47 (1H, m), 7.01 (1H, br. s.), 6.38 (1H, br. s.), 3.89-4.06 (4H, m), 3.76 (4H, t, J=4.6 Hz), 3.37-3.56 (2H, m), 2.93-3.28 (9H, m), 2.03 (3H, s). Mass Spectrum (ESI) m/e=623.3.3 (M+1).