反应详情

温度

23 °C

To sodium hydride (60 wt % in mineral oil, 1.58 g, 39.6 mmol) in tetrahydrofuran (50 mL) at 23° C., add 3-butyn-1-ol (7.93 g, 8.59 mL, 113.2 mmol) dropwise, then stir at 23° C. for 20 minutes. Add this solution to 2-chloro-1-[2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]ethanone (9.70 g, 28.3 mmol) in tetrahydrofuran (150 mL) at 23° C. and stir for one hour. Pour the reaction mixture into 50% saturated aqueous sodium bicarbonate solution. Separate the organic layer and further extract the aqueous layer with ethyl ether (×2) and ethyl acetate (×2). Combine the organic extracts and wash with brine, then dry over anhydrous sodium sulfate, filter, and concentrate. Purify the resulting crude product by silica gel column chromatography (gradient elution: 20% ethyl acetate in hexanes to 100% ethyl acetate) to give the title compound (8.16 g, 77%). MS (m/z): 377 (M+1).

1. stirringstir for one hour
2. customSeparate the organic layer
3. extractionfurther extract the aqueous layer with ethyl ether (×2) and ethyl acetate (×2)
4. washCombine the organic extracts and wash with brine
5. dry with materialdry over anhydrous sodium sulfate
6. filtrationfilter
7. concentrationconcentrate
8. customPurify the resulting crude product
9. washby silica gel column chromatography (gradient elution: 20% ethyl acetate in hexanes to 100% ethyl acetate)