反应详情

Add to a solution of trans-{4-[6-(1-benzyl-piperidin-4-ylamino)-9-isopropyl-9H-purin-2-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester (8b, Ig, 1 mmol) and methanol (40 ml), a suspension of palladium black (0.25 g) in a little water. Then add a solution of ammonium formate (0.4 mg, 6.4 mmol) and 10 ml of water, and reflux overnight. Filter the reaction through Celite® and concentrate the filtrate to dryness. Dissolve the residue in methylene chloride (50 ml), extracted with water, and filter through Celite® to remove a milky white precipitate. Separate the organic layer, wash with brine, dry over sodium sulfate, filter and concentrate the filtrate to dryness. Purify the residue on a 40 gram silica gel column (Biotage) using DCM/methanol (4:1) to give 0.8 grams of trans-{4-[9-isopropyl-6-(piperidin-4-ylamino)-9H-purin-2-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester (9b). H1-NMR (CDCl3): δ 7.5 (s, 1H), 5.45 (brs, 1H), 4.64 (m, 2H), 4.45 (m, 1H), 4.2 (m, 1H), 3.75 (m, 1H), 3.5 (m, 1H), 3.2 (m, 1H), 3.0 (m, 1H), 2.8 (t, 1H), 2.5-2.0 (m, 9H), 1.6 (m, 2H), 1.53 (d, 6H), 1.45 (s, 9H), 1.25 (m, 3H).

1. temperaturereflux overnight
2. filtrationFilter
3. customthe reaction through Celite®
4. concentrationconcentrate the filtrate to dryness
5. dissolutionDissolve the residue in methylene chloride (50 ml)
6. extractionextracted with water
7. filtrationfilter through Celite®
8. customto remove a milky white precipitate
9. customSeparate the organic layer
10. washwash with brine
11. dry with materialdry over sodium sulfate
12. filtrationfilter
13. concentrationconcentrate the filtrate to dryness
14. customPurify the residue on a 40 gram silica gel column (Biotage)