反应详情

NaH (5.26 g, 131 mmol) was added to a solution of ethyl 4-amino-2-(methylthio)pyrimidine-5-carboxylate (20.0 g, 94 mmol, US 2005/0020590) in N,N-dimethylformamide (700 mL) at 0° C. After 10 minutes, 1-chloro-2-isocyanatobenzene (15.9 mL, 131 mmol) was added dropwise to the mixture. The reaction was warmed to room temperature and stirred for 6 hours. The reaction mixture was diluted with brine (200 mL) and water (1000 mL) and extracted with ether (700 mL 2×). The aqueous layer was acidified with 5% citric acid (until pH=4-5), treated with brine, and extracted with ethyl acetate (2×). The combined organic layers were washed with water (2×), dried over MgSO4, filtered, and concentrated to remove most of the solvent. The mixture was filtered, and the solid was washed with cold ethyl acetate, and oven dried to provide the title compound.

1. extractionextracted with ether (700 mL 2×)
2. additiontreated with brine
3. extractionextracted with ethyl acetate (2×)
4. washThe combined organic layers were washed with water (2×)
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. customto remove most of the solvent
9. filtrationThe mixture was filtered
10. washthe solid was washed with cold ethyl acetate, and oven
11. customdried