反应详情

A mixture of 2-{[(2,6-dichloropyridin-3-yl)methyl]sulfanyl}-6-methylpyrimidin-4-ol (2.0 g, 6.61 mmol) and 1-ethylpiperazine (3.77 g, 26.88 mmol) was heated in DMSO (20 mL) at 90° C. overnight. After cooling, the mixture was extracted with ethyl acetate (2×100 mL). The organic layer was separated and washed with water and brine. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated to dryness and purified by CombiFlash chromatography using 0-20% dichloromethane:methanol to provide 2-({[2-chloro-6-(4-ethylpiperazin-1-yl)pyridin-3-yl]methyl}sulfanyl)-6-methylpyrimidin-4-ol (1H NMR (400 MHz, DMSO-d6): δ 1.02 (t, 3H), 2.18 (s, 3H), 2.31 (q, 2H), 2.56 (m, 4H), 3.42 (m, 4H), 4.30 (s, 2H), 6.01 (bs, 1H), 6.78 (d, J=8.4 Hz, 1H), 7.72 (d, J=8.4 Hz, 1H), LRMS (ES) m/z 379.8) and 2-({[6-chloro-2-(4-ethylpiperazin-1-yl)pyridin-3-yl]methyl}sulfanyl)-6-methylpyrimidin-4-ol (1H NMR (400 MHz, DMSO-d6): δ 0.99 (t, 3H), 2.21 (s, 3H), 2.31 (q, 2H), 2.56 (m, 4H), 3.42 (m, 4H), 4.37 (s, 2H), 6.01 (bs, 1H), 7.06 (d, J=7.7 Hz, 1H), 7.77 (d, J=7.7 Hz, 1H), LRMS (ES) m/z 379.8) as a white solid (1.73 g, 3:1 ratio, 69% yield).

1. temperatureAfter cooling
2. extractionthe mixture was extracted with ethyl acetate (2×100 mL)
3. customThe organic layer was separated
4. washwashed with water and brine
5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
6. filtrationfiltered
7. customThe filtrate was evaporated to dryness
8. custompurified by CombiFlash chromatography