Dichloromethane → HCID 178454031, compound

HRID 982875Notes

Reaction equation

HRID 982875 reaction equation
[C:1]([O:5][C:6](=[O:43])[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]3[CH2:28][CH2:27][CH2:26][CH2:25]3)=[C:17]([NH:29][CH:30]3[CH2:35][CH2:34][N:33](CC4C=CC=CC=4)[CH2:32][CH2:31]3)[N:16]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C([O-])=O.[NH4+].C(Cl)Cl>CO.O.[Pd]>[C:1]([O:5][C:6](=[O:43])[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]3[CH2:28][CH2:27][CH2:26][CH2:25]3)=[C:17]([NH:29][CH:30]3[CH2:31][CH2:32][NH:33][CH2:34][CH2:35]3)[N:16]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 6344DichloromethaneHCID 2723923Ammonium formate2×HCID 178454033HCID 178454033, compound

Product 1

HCID 178454031HCID 178454031, compoundYield 98.5%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×HCID 962WaterSolvent2×

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-73a9ed33753a475e94429a432d2e4421
Source dataset
uspto-grants-2005_03
Patent number
US06861524B2

Reaction notes

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