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

HRID 2403805Notes

Reaction equation

HRID 2403805 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][CH2:34][CH:35]1[CH2:40][CH2:39][CH2:38][CH2:37][N:36]1[C:41]([O:43][CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)=[O:42]>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][CH2:34][CH:35]1[CH2:40][CH2:39][CH2:38][CH2:37][N:36]1[C:41]([O:43][CH2:44][C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1)=[O:42]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 58306190Benzyl 2-(3-bromopropyl)piperidine-1-carboxylateHCID 178450370HCID 178450370, compound

Product 1

HCID 58306132Phenylmethyl 2-{3-[6-amino-2-(butyloxy)-8-(methyloxy)-9H-purin-9-yl]propyl}-1-piperidinecarboxylateYield 44.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(Butyloxy)-8-(methyloxy)-9H-purin-6-amine trifluoroacetate (1.834 g, 5.22 mmol) was heated at 60° C. with potassium carbonate (2.89 g, 20.88 mmol) in DMF (23 ml) for 1 hour. Phenylmethyl 2-(3-bromopropyl)-1-piperidinecarboxylate (2.131 g, 6.26 mmol) was added and heating continued 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 ethyl acetate (100 ml). The combined organic layers were washed with brine (100 ml) and passed through a hydrophobic frit to dry, then stripped to dryness (rotary evaporator) to give an orange liquid. The material was loaded onto 2×70 g aminopropyl cartridge and eluted on the Flashmaster system in gradient of 0-100% ethylacetate in cyclohexane over 40 mins. Appropriate product fractions were combined and evaporated in vacuo to give the title compound as a clear oil (1.16 g).

Workup

  1. temperatureheating
  2. custom(20 hours)
  3. customThe reaction mixture was partitioned between water (250 mL) and ethyl acetate (150 mL)
  4. extractionThe aqueous was further extracted with ethyl acetate (100 ml)
  5. washThe combined organic layers were washed with brine (100 ml)
  6. customto dry
  7. customstripped to dryness (rotary evaporator)
  8. customto give an orange liquid
  9. washeluted on the Flashmaster system in gradient of 0-100% ethylacetate in cyclohexane over 40 mins
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-6c089e7df5fd46b5b5d73d131039ab38
Source dataset
uspto-grants-2014_08
Patent number
US08802684B2

Reaction notes

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