反应详情

Add to a solution of {4-[6-(1-benzyl-piperidin-4-ylamino)-9-cyclopentyl-9H-purin-2-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester (8a, 40.2 g, 68 mmol) in 400 mL of methanol, a suspension of Pd black (2 g) in a small amount of water. Then add a solution of ammonium formate (13.3 g, 215 mmol) in 100 mL of water, and heat at a gentle reflux overnight. TLC shows the presence of starting material (TLC, silica plates, 4:1 DCM:methanol; Rf: starting material 0.75, product 0.15). Add an additional 5 g of ammonium formate and reflux 24 hours. Remove the catalyst by filtration through Celite® and concentrate the filtrate. Dissolve the residue in DCM and extract with water. Remove the white precipitate by filtration through a pad of Celite®, wash the filtrate with brine, dry over sodium sulfate and filter. Concentrate the filtrate and purify the residue on silica gel (500 g) using DCM:methanol (4:1) to give 33.4 g of trans-{4-[9-cyclopentyl-6-(piperidin-4-ylamino)-9H-purin-2-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester (9a) as a white solid.

1. temperatureheat at
2. temperaturea gentle reflux overnight
3. temperaturereflux 24 hours
4. customRemove the catalyst
5. filtrationby filtration through Celite®
6. concentrationconcentrate the filtrate
7. dissolutionDissolve the residue in DCM
8. extractionextract with water
9. customRemove the white precipitate
10. filtrationby filtration through a pad of Celite®
11. washwash the filtrate with brine
12. dry with materialdry over sodium sulfate
13. filtrationfilter
14. concentrationConcentrate the filtrate
15. custompurify the residue on silica gel (500 g)