Potassium Carbonate → 2-(Butyloxy)-9-{2-[1-(1-methylethyl)-4-piperidinyl]ethyl}-8-(methyloxy)-9H-purin-6-amine

HRID 1044910Notes

Reaction equation

HRID 1044910 reaction equation
F[C:2](F)(F)[C:3](O)=O.C[C@H:9]([O:13][C:14]1[NH:15][C:16]([NH2:25])=[C:17]2[C:21]([N:22]=1)=[N:20][C:19]([O:23][CH3:24])=[N:18]2)[CH2:10][CH2:11][CH3:12].[C:26](=O)([O-])[O-].[K+].[K+].Br[CH2:33][CH2:34][CH:35]1[CH2:40][CH2:39][N:38](C(OCC2C=CC=CC=2)=O)[CH2:37][CH2:36]1>CN(C=O)C.C(Cl)Cl.O>[CH2:9]([O:13][C:14]1[N:22]=[C:21]2[C:17]([N:18]=[C:19]([O:23][CH3:24])[N:20]2[CH2:33][CH2:34][CH:35]2[CH2:40][CH2:39][N:38]([CH:3]([CH3:2])[CH3:26])[CH2:37][CH2:36]2)=[C:16]([NH2:25])[N:15]=1)[CH2:10][CH2:11][CH3:12]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 11056468Benzyl 4-(2-bromoethyl)piperidine-1-carboxylate2×HCID 178448285HCID 178448285, compound

Product 1

HCID 583062702-(Butyloxy)-9-{2-[1-(1-methylethyl)-4-piperidinyl]ethyl}-8-(methyloxy)-9H-purin-6-amineYield 42.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

2-{[(1S)-1-methylbutyl]oxy}-8-(methyloxy)-1H-purin-6-amine trifluoroacetate (250 mg, 0.684 mmol) and potassium carbonate (236 mg, 1.711 mmol) were dissolved in DMF (4 ml) and heated at 60° C. for 1 hour. The reaction mixture was cooled to room temperature and phenylmethyl 4-(2-bromoethyl)-1-piperidinecarboxylate (223 mg, 0.684 mmol) added. The reaction was then heated to 50° C. for a further 18 hours. Phenylmethyl 4-(2-bromoethyl)-1-piperidinecarboxylate (45 mg, 0.147 mmol) was added and the reaction heated at 50° C. for a further 18 hours. The reaction mixture was diluted with DCM (5 ml) and water (5 ml) and the layers separated using a hydrophobic frit. The aqueous was washed with further DCM (5 ml) and the combined organics concentrated. The residue was purified by column chromatography, the sample was loaded in dichloromethane onto silica (Si) 20 g and eluted using a gradient of 0-100% ethyl acetate in cyclohexane+0-20% methanol over 40 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a yellow glass (114 mg).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. temperatureThe reaction was then heated to 50° C. for a further 18 hours
  3. temperaturethe reaction heated at 50° C. for a further 18 hours
  4. customthe layers separated
  5. washThe aqueous was washed with further DCM (5 ml)
  6. customThe residue was purified by column chromatography
  7. washeluted
  8. customover 40 mins
  9. customevaporated in vacuo

Sources & evidence

ORD record
ord-cd0449e6dc82434dae3726a69254c9b9
Source dataset
uspto-grants-2013_10
Patent number
US08563717B2

Reaction notes

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