Water → HCID 58306206, compound

HRID 1044850Notes

Reaction equation

HRID 1044850 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]([CH2:39][CH3:40])[CH2:34]1.O>CN(C)C=O>[CH2:8]([O:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[C:18]([O:22][CH3:23])[N:19]2[CH2:32][CH:33]2[CH2:38][CH2:37][CH2:36][N:35]([CH2:39][CH3:40])[CH2:34]2)=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 215104883-(Bromomethyl)-1-ethylpiperidineHCID 178450370HCID 178450370, compound

Product 1

HCID 58306206HCID 58306206, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A stirring mixture of 2-butoxy-8-methoxy-9H-purin-6-amine trifluoroacetate salt (200 mg) and potassium carbonate (236 mg) in dry N,N-dimethylformamide (2 ml) was heated with stirring at 60° C. for 1 hour. 3-(Bromomethyl)-1-ethylpiperidine (141 mg) was added and the stirring mixture heated at 50° C. for 3 hours. After 16 hours at ambient temperature, heating at 50° C. was continued for a further 3 hours to complete the reaction. Water was added and the mixture extracted three times with ethyl acetate. The combined extracts were washed with water then brine, dried by passing through a phase separation cartridge and stripped to give a brown oil. This was purified by C18 reverse phase chromatography using water (containing 0.1% formic acid)-acetonitrile (containing 0.05% formic acid) as eluent (10-45%) and the appropriate fractions combined and evaporated to remove acetonitrile. The remaining aqueous mixture was made basic with saturated sodium hydrogen carbonate, extracted three times with dichloromethane and the combined extracts dried by passing through a phase separation cartridge then evaporated to afford the title compound as a white solid (99 mg).

Workup

  1. temperaturewas heated
  2. temperaturethe stirring mixture heated at 50° C. for 3 hours
  3. waitAfter 16 hours at ambient temperature
  4. temperatureheating at 50° C.
  5. waitwas continued for a further 3 hours
  6. customthe reaction
  7. extractionthe mixture extracted three times with ethyl acetate
  8. washThe combined extracts were washed with water
  9. dry with materialbrine, dried
  10. customby passing through a phase separation cartridge
  11. customto give a brown oil
  12. customThis was purified by C18 reverse phase chromatography
  13. customevaporated
  14. customto remove acetonitrile
  15. extractionextracted three times with dichloromethane
  16. customthe combined extracts dried
  17. customby passing through a phase separation cartridge
  18. customthen evaporated

Sources & evidence

ORD record
ord-4b90c6a22e5d4d6cacdd6eb0d58bb2f3
Source dataset
uspto-grants-2013_10
Patent number
US08563717B2

Reaction notes

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