Water → HCID 58306204, compound

HRID 2403787Notes

Reaction equation

HRID 2403787 reaction equation
FC(F)(F)C(O)=O.[CH2:8]([NH: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]([NH: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 178448879HCID 178448879, compound

Product 1

HCID 58306204HCID 58306204, compoundYield 58.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A stirring mixture of N2-butyl-8-methoxy-9H-purine-2,6-diamine trifluoroacetic acid 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 6 hours. After 72 hours at ambient temperature heating at 50° C. was continued for a further 6 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 (5-35%) 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 clear oil (120 mg).

Workup

  1. temperaturewas heated
  2. temperaturethe stirring mixture heated at 50° C. for 6 hours
  3. temperatureAfter 72 hours at ambient temperature heating at 50° C.
  4. waitwas continued for a further 6 hours
  5. customthe reaction
  6. extractionthe mixture extracted three times with ethyl acetate
  7. washThe combined extracts were washed with water
  8. dry with materialbrine, dried
  9. customby passing through a phase separation cartridge
  10. customto give a brown oil
  11. customThis was purified by C18 reverse phase chromatography
  12. customevaporated
  13. customto remove acetonitrile
  14. extractionextracted three times with dichloromethane
  15. customthe combined extracts dried
  16. customby passing through a phase separation cartridge
  17. customthen evaporated

Sources & evidence

ORD record
ord-13b77ce54c654de185db54d167b589f0
Source dataset
uspto-grants-2014_08
Patent number
US08802684B2

Reaction notes

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