Potassium Carbonate → Phenylmethyl 3-{[6-amino-2-(butyloxy)-8-(methyloxy)-9H-purin-9-yl]methyl}-1-piperidinecarboxylate

HRID 2403807Notes

Reaction equation

HRID 2403807 reaction equation
FC(F)(F)C(O)=O.[CH2:8]([O:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[C:18]([O:22][CH3:23])[NH:19]2)=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11].C(=O)([O-])[O-].[K+].[K+].Br[CH2:32][CH:33]1[CH2:38][CH2:37][CH2:36][N:35]([C:39]([O:41][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[O:40])[CH2:34]1>CN(C=O)C.O.CS(C)=O>[NH2:24][C:15]1[N:14]=[C:13]([O:12][CH2:8][CH2:9][CH2:10][CH3:11])[N:21]=[C:20]2[C:16]=1[N:17]=[C:18]([O:22][CH3:23])[N:19]2[CH2:32][CH:33]1[CH2:38][CH2:37][CH2:36][N:35]([C:39]([O:41][CH2:42][C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)=[O:40])[CH2:34]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 23000675Benzyl 3-(bromomethyl)piperidine-1-carboxylateHCID 178450370HCID 178450370, compound

Product 1

HCID 58306120Phenylmethyl 3-{[6-amino-2-(butyloxy)-8-(methyloxy)-9H-purin-9-yl]methyl}-1-piperidinecarboxylate

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-(butyloxy)-8-(methyloxy)-9H-purin-6-amine. trifluoroacetate salt (2.56 g, 7.29 mmol) in DMF (60 ml) was added potassium carbonate (4.03 g, 29.1 mmol) and the mixture was left to stir at 60° C. for one hour under an atmosphere of nitrogen. Reaction was then cooled to room temperature and to this was added phenylmethyl 3-(bromomethyl)-1-piperidinecarboxylate (2.275 g, 7.29 mmol). The reaction was bought back up to 50° C. and left to stir overnight. The reaction mixture was diluted with water (˜40 ml) and partitioned with a solvent mix of 1:1 ethyl acetate:DCM (40 ml). The organic layer was separated using hydrophobic frit and was concentrated in vacuo to give pale yellow thick oil. The crude material was dissolved in 1:1 DMSO:MeOH (5 ml) and half of this solution was initially purified on reverse-phase chromatography using a high pH system on a 330 g C18 silica column. The gradient used was the following:

Workup

  1. waitthe mixture was left
  2. customReaction
  3. temperaturewas then cooled to room temperature
  4. customwas bought back up to 50° C.
  5. waitleft
  6. stirringto stir overnight
  7. custompartitioned with a solvent
  8. additionmix of 1:1 ethyl acetate
  9. customThe organic layer was separated
  10. concentrationwas concentrated in vacuo
  11. customto give pale yellow thick oil
  12. customMeOH (5 ml) and half of this solution was initially purified on reverse-phase chromatography

Sources & evidence

ORD record
ord-86ec9434238d45eb960cf9c5659ed5ad
Source dataset
uspto-grants-2014_08
Patent number
US08802684B2

Reaction notes

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