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

HRID 1044866Notes

Reaction equation

HRID 1044866 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][CH2:33][CH:34]1[CH2:39][CH2:38][CH2:37][CH2:36][N:35]1[C:40]([O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:41]>CN(C=O)C>[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][CH2:33][CH:34]1[CH2:39][CH2:38][CH2:37][CH2:36][N:35]1[C:40]([O:42][CH2:43][C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1)=[O:41]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 58306210Benzyl 2-(2-bromoethyl)piperidine-1-carboxylateHCID 178450370HCID 178450370, compound

Product 1

HCID 58306137Phenylmethyl 2-{2-[6-amino-2-(butyloxy)-8-(methyloxy)-9H-purin-9-yl]ethyl}-1-piperidinecarboxylateYield 18.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

2-(Butyloxy)-8-(methyloxy)-9H-purin-6-amine trifluoroacetate (1.346 g, 3.83 mmol) was heated with anhydrous potassium carbonate (2.118 g, 15.33 mmol) in dry DMF (17 ml) at 60° C. for 1 hour. Phenylmethyl 2-(2-bromoethyl)-1-piperidinecarboxylate (1.500 g, 4.60 mmol) was added and the reaction mixture heated at 50° C. overnight (20 hours). The reaction mixture was partitioned between water (250 ml) and ethyl acetate (150 ml). The aqueous was further extracted with 2×100 ml ethyl acetate. The combined organic layers were washed with 100 ml brine and passed through a hydrophobic frit to dry, then stripped to dryness (rotary evaporator). The residue was dissolved in DCM and loaded onto a 70 g silica cartridge and purified by chromatography using a gradient 0-100% ethyl acetate in dichloromethane+0-12% MeOH finish on a Flashmaster 2. Appropriate fractions were combined and evaporated in vacuo. The material was re-purified by chromatography on silica (70 g cartridge using a gradient of 0-100% ethyl acetate in dichloromethane over 40 mins. and subsequently a flush of 0-100% ethyl acetate in DCM+0-20% MeOH). Product fractions combined and evaporated in vacuo to give the title compound as a colourless oil (0.342 g).

Workup

  1. customThe reaction mixture was partitioned between water (250 ml) and ethyl acetate (150 ml)
  2. extractionThe aqueous was further extracted with 2×100 ml ethyl acetate
  3. washThe combined organic layers were washed with 100 ml brine
  4. customto dry
  5. customstripped to dryness (rotary evaporator)
  6. dissolutionThe residue was dissolved in DCM
  7. custompurified by chromatography
  8. customevaporated in vacuo
  9. customThe material was re-purified by chromatography on silica (70 g cartridge
  10. customover 40 mins
  11. customand subsequently a flush of 0-100% ethyl acetate in DCM+0-20% MeOH)
  12. customevaporated in vacuo

Sources & evidence

ORD record
ord-02759725348e431782281c94cbe1929a
Source dataset
uspto-grants-2013_10
Patent number
US08563717B2

Reaction notes

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