反应详情

To a stirred solution of tris trimethylsilylguanine (16.5 g) in toluene (50 ml) was added N-(2-chloromethoxyethyl)phthalimide (17.0 g) and triethylamine (23 ml). The reaction mixture was heated at reflux under nitrogen for 29 hours, cooled and evaporated under reduced pressure giving a dark brown oil. The oil was digested in ethanol (400 ml) on a steam bath for 40 minutes, giving a solid which was collected and washed with ethanol and ether. It was recrystallized from 2-methoxyethanol to give 9-(2-phthalimidoethoxymethyl)guanine hydrate (14.4 g), m.p. >240° C. (dec.). A mixture of 9-(2-phthalimidoethoxymethyl)guanine hydrate (0.94 g), hydrazine (2 ml) and ethanol (100 ml) was heated at reflux with stirring for one hour. The reaction mixture was filtered hot, and the filtrate was cooled and evaporated under reduced pressure. Ethanol was added and the mixture re-evaporated. This was repeated three times. The residual solid was stirred with 3% aqueous acetic acid (50 ml) for 30 minutes and filtered. The solids were washed with water (15 ml), and the wash and filtrate combined. The combined wash and filtrate was evaporated under reduced pressure at <35° C. to a small volume, diluted with ethanol and evaporated to dryness. The pasty, white solid was dispersed in a small amount of ethanol and diluted with a few ml ether to give a granular solid which was collected, washed with ethanol and dried. Recrystallization from ethanol-water gave 9-(2-aminoethoxymethyl)guanine acetate monohydrate (0.43 g), m.p. (~135° C. melts and resolidifies) 174°-176° C.

1. temperaturewas heated
2. temperatureat reflux
3. filtrationThe reaction mixture was filtered hot
4. temperaturethe filtrate was cooled
5. customevaporated under reduced pressure
6. additionEthanol was added
7. customthe mixture re-evaporated
8. stirringThe residual solid was stirred with 3% aqueous acetic acid (50 ml) for 30 minutes
9. filtrationfiltered
10. washThe solids were washed with water (15 ml)
11. washthe wash
12. washThe combined wash
13. customfiltrate was evaporated under reduced pressure at <35° C. to a small volume
14. additiondiluted with ethanol
15. customevaporated to dryness
16. additionThe pasty, white solid was dispersed in a small amount of ethanol
17. additiondiluted with a few ml ether
18. customto give a granular solid which
19. customwas collected
20. washwashed with ethanol
21. customdried
22. customRecrystallization from ethanol-water