反应详情

温度

50 °C

Sodium t-butoxide (3.31 g, 34.2 mmol) was added portionwise to cyclobutanol (10 ml) at room temperature. The mixture became very thick and was heated to 50° C. 2-Fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (2 g, 8.43 mmol) was added followed by 1,2-dimethoxyethane (3 ml) and the mixture stirred at 50° C. for 90 mins. and then cooled and partitioned between ethyl acetate (50 ml) and water (50 ml). A precipitate that failed to dissolve in either phase was removed by filtration. The organic phase was separated, washed with saturated brine, dried over anhydrous magnesium sulphate, filtered and evaporated to give a cream foam. This material was dissolved in dichloromethane and purified on an aminopropyl (NH2) cartridge (110 g) using a 0-100% ethyl acetate in cyclohexane gradient followed by a 0-20% methanol (+1% triethylamine) gradient over 40 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as an off-white solid (0.655 g).

1. temperatureand then cooled
2. custompartitioned between ethyl acetate (50 ml) and water (50 ml)
3. dissolutionto dissolve in either phase
4. customwas removed by filtration
5. customThe organic phase was separated
6. washwashed with saturated brine
7. dry with materialdried over anhydrous magnesium sulphate
8. filtrationfiltered
9. customevaporated
10. customto give a cream foam
11. custompurified on an aminopropyl (NH2) cartridge (110 g)
12. waitfollowed by a 0-20% methanol (+1% triethylamine) gradient over 40 mins
13. customevaporated in vacuo