反応 #615000

反応方程式

Sodium tert-butoxide

cyclohexanol

2-Fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

cyclohexanol

→

title compound

2-(Cyclohexyloxy)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

反応条件

後処理

1. 1
   温度the mixture heated at 50° C. for 1 hour
2. 2
   温度warmed to 60° C.
3. 3
   温度heated for a further 2 hours at which point LCMS
4. 4
   その他reaction
5. 5
   温度The mixture was cooled to room temperature
6. 6
   その他partitioned between ethyl acetate (150 ml) and water (150 ml)
7. 7
   その他The organic phase was separated
8. 8
   洗浄washed with saturated brine
9. 9
   乾燥dried over anhydrous magnesium sulphate
10. 10
    ろ過filtered
11. 11
    その他evaporated on a water bath at 60° C
12. 12
    workup.DISSOLUTIONThe residue was dissolved in dichloromethane
13. 13
    その他purified on a 70 g aminopropyl (NH2) cartridge
14. 14
    その他these were re-purified on a 70 g silica cartridge
15. 15
    その他over 40 mins
16. 16
    その他evaporated in vacuo

実験手順

Sodium tert-butoxide (3.29 g, 34.2 mmol) was added portionwise to cyclohexanol (15 ml) at room temperature. The mixture became very thick and more cyclohexanol (10 ml) was added and the mixture heated to 50° C. 2-Fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (2 g, 8.43 mmol) was added and the mixture heated at 50° C. for 1 hour and then warmed to 60° C. and heated for a further 2 hours at which point LCMS showed complete reaction. The mixture was cooled to room temperature and partitioned between ethyl acetate (150 ml) and water (150 ml). The organic phase was separated, washed with saturated brine, dried over anhydrous magnesium sulphate, filtered and evaporated on a water bath at 60° C. The residue was dissolved in dichloromethane and purified on a 70 g aminopropyl (NH2) cartridge using a 0-100% ethyl acetate in cyclohexane gradient followed by a 0-20% methanol (+1% triethylamine) gradient over 30 mins. Some product-containing fractions were contaminated with cyclohexanol and these were re-purified on a 70 g silica cartridge using a 0-100% ethyl acetate-cyclohexane gradient over 40 mins. Product-containing fractions from the two purifications were combined and evaporated in vacuo to give the title compound as a pale yellow foam (1.59 g).

出典