Methanol → HCID 178456427, compound

HRID 33360Notes

Reaction equation

HRID 33360 reaction equation
[C:1]([O:5][C:6](=[O:41])[NH:7][C@H:8]1[CH2:13][CH2:12][C@H:11]([NH:14][C:15]2[N:23]=[C:22]3[C:18]([N:19]=[CH:20][N:21]3[CH:24]([CH3:26])[CH3:25])=[C:17]([NH:27][CH:28]3[CH2:33][CH2:32][N:31](CC4C=CC=CC=4)[CH2:30][CH2:29]3)[N:16]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].CO.C([O-])=O.[NH4+]>[Pd].O>[C:1]([O:5][C:6](=[O:41])[NH:7][C@H:8]1[CH2:13][CH2:12][C@H:11]([NH:14][C:15]2[N:23]=[C:22]3[C:18]([N:19]=[CH:20][N:21]3[CH:24]([CH3:26])[CH3:25])=[C:17]([NH:27][CH:28]3[CH2:29][CH2:30][NH:31][CH2:32][CH2:33]3)[N:16]=2)[CH2:10][CH2:9]1)([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 3

HCID 887MethanolHCID 2723923Ammonium formateHCID 178456428HCID 178456428, compound

Product 1

HCID 178456427HCID 178456427, compoundYield 169.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent2×

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-3233ba0896b5498db2a6e52c74195be4
Source dataset
uspto-grants-2008_09
Patent number
US07429595B2

Reaction notes

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