反应详情

温度

80 °C

Methyl 3-[4-[(2,4-difluorobenzyl)oxy]-2-(methylthio)-6-oxopyrimidin-1(6H)-yl]-4-methylbenzoate (87 g, 0.20 mol) was dissolved in N,N-dimethylacetamide (870 mL) and heated to 80° C. Raney Ni was added and slight exotherm and off-gassing were observed. Reaction was complete. Heat and stirring were turned off. Since product had begun to precipitate from the cooled reaction mixture, heat was turned back on to 70° C. and stirring resumed. After redissolving the precipitate, the reaction mixture was allowed to cool for 15 min and then filtered through celite. Rinsed with 50° C. DMA and water, being careful not to let the celite pad go dry. The filtrate was added to 2 L of water and stirred. Product filtered, rinsed with water, and dried in the vacuum oven. When found to still be wet with DMA, slurried with water and stirred 1 h before filtering and redrying. Obtained the product as a white solid (63 g, 81%). 1H NMR (CD3OD/400 MHz) δ8.28 (s, 1H), 8.04 (m, 1H), 7.90 (s, 1H), 7.55 (m, 2H), 6.99 (m, 2H), 5.87 (s, 1H), 5.39 (s, 2H), 3.88 (s, 3H), 2.19 (s, 3H). ESHRMS m/z 387.1195 (M+H calculated for C20H17F2N2O4 requires 387.1151).

1. customReaction
2. temperatureHeat
3. customto precipitate from the cooled reaction mixture
4. temperatureheat
5. customwas turned back on to 70° C.
6. stirringstirring
7. dissolutionAfter redissolving the precipitate
8. temperatureto cool for 15 min
9. filtrationfiltered through celite
10. washRinsed with 50° C
11. customgo dry
12. additionThe filtrate was added to 2 L of water
13. stirringstirred
14. filtrationProduct filtered
15. washrinsed with water
16. customdried in the vacuum oven
17. stirringstirred 1 h
18. filtrationbefore filtering
19. customredrying