反应详情

Charge a 100 mL flask with 2-[8-(2-chlorophenyl)-9-(2-hydroxyethyl)-2-methyl-purin-6-yl]-1,3,4,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-6-one, Isomer-2 [C09111070-E] (3.3 g, 7.73 mmol) and DMF (35 mL) followed by methyl iodide (1.24 g, 8.50 mmol). Add 60% NaH (0.59 g, 13.9 mmol) in portions at 10-25° C. and stir for 2 h. Pour the mixture into water (100 mL) while stirring and extract the solution with ethyl acetate (3×50 mL). Combine the organic layers, wash with water (2×50 mL), and concentrate under vacuum to give an oil. Purify the crude by silica gel (100 g) column chromatography eluting with dichloromethane/methanol (50:1) to give a yellow solid. Redissolve the solid in ethyl acetate (40 mL) and add a solution of 1 N HCl in ethyl acetate slowly until a solid precipitates. Stir at room temperature for 2 h, filter the cake, and wash with ethyl acetate (10 mL). Dry the cake under vacuum to give 2.8 g of the title compound as an off-white solid (98.0% ee); ES/MS m/z 441.3 (M+1).

1. stirringwhile stirring
2. extractionextract the solution with ethyl acetate (3×50 mL)
3. washCombine the organic layers, wash with water (2×50 mL)
4. concentrationconcentrate under vacuum
5. customto give an oil
6. customPurify the crude by silica gel (100 g) column chromatography
7. washeluting with dichloromethane/methanol (50:1)
8. customto give a yellow solid
9. customprecipitates
10. stirringStir at room temperature for 2 h
11. filtrationfilter the cake
12. washwash with ethyl acetate (10 mL)
13. customDry the cake under vacuum