反应详情

温度

130 °C

A mixture of 1-((2-(methylsulfinyl)benzo[d]thiazol-6-yl)methyl)-3-morpholino pyrazin-2(1H)-one (250 mg, 0.64 mmol), (1R,2R)-2-aminocyclohexanol (221 mg, 1.92 mmol) and DIEA (248 mg, 1.92 mmol) in DMA (6.6 mL) was stirred at 130° C. for 16 h. The reaction mixture was cooled to rt and poured into water (30 mL). The mixture extracted with ethyl acetate (3×100 mL) and the combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 1:5 petroleum ether/ethyl acetate to give 1-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-3-morpholinopyrazin-2(1H)-one as a light yellow solid (120 mg, 26.5%). 1H NMR (300 MHz, DMSO-d6) δ 7.96 (d, J=7.2 Hz, 1H), 7.63 (s, 1H), 7.30 (d, J=8.4 Hz, 1H), 7.18-7.22 (m, 2H), 6.90 (d, J=4.8 Hz, 1H), 5.01 (s, 2H), 4.72 (d, J=5.1 Hz, 1H), 3.65 (s, 8H), 3.55-3.52 (m, 1H), 3.36-3.31 (m, 1H), 2.07-2.02 (m, 1H), 1.90-1.86 (m, 1H), 1.63-1.62 (m, 2H), 1.30-1.22 (m, 4H). LCMS (ESI) m/z 442 (M+H)+.

1. temperatureThe reaction mixture was cooled to rt
2. extractionThe mixture extracted with ethyl acetate (3×100 mL)
3. washthe combined organic layers were washed with brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by silica gel chromatography
8. washeluting with 1:5 petroleum ether/ethyl acetate