反应详情

A solution of N-[(4aR,7aS)-7a-(3-aminophenyl)-4a,5,6,7-tetrahydro-4H-pyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (2.49 g, 7.06 mmol), 5-fluoro-2-chloropyrimidine (3.74 g, 28.26 mmol), and diisopropylethylamine (6.16 mL, 35.32 mmol) in 1,4-dioxane (60 mL) is heated to reflux for 4 hours under nitrogen. The reaction is cooled, diluted with water and extracted with ethyl acetate (3×). The combined organic extracts are dried over sodium sulfate, filtered and the solvent is removed in vacuo to give the crude product. The crude product is purified over silica gel with a 25 minute 5% to 100% ethyl acetate in hexanes gradient to give the title compound (2.51 g, 79%). ES/MS (m/e): 449 (M+H).

1. temperatureto reflux for 4 hours under nitrogen
2. temperatureThe reaction is cooled
3. extractionextracted with ethyl acetate (3×)
4. dry with materialThe combined organic extracts are dried over sodium sulfate
5. filtrationfiltered
6. customthe solvent is removed in vacuo
7. customto give the crude product
8. customThe crude product is purified over silica gel with a 25 minute 5% to 100% ethyl acetate in hexanes gradient