Potassium Carbonate → N2-Butyl-8-(methoxy)-9-[2-(tetrahydro-2H-pyran-2-yl)ethyl]-9H-Purine-2,6-diamine

HRID 1010994Notes

Reaction equation

HRID 1010994 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+].CS(O[CH2:36][CH2:37][CH:38]1[CH2:43][CH2:42][CH2:41][CH2:40][O:39]1)(=O)=O>CN(C=O)C>[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[CH2:36][CH2:37][CH:38]2[CH2:43][CH2:42][CH2:41][CH2:40][O:39]2)=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 576998282-(Oxan-2-yl)ethyl methanesulfonateHCID 178448879HCID 178448879, compound

Product 1

HCID 57699622N2-Butyl-8-(methoxy)-9-[2-(tetrahydro-2H-pyran-2-yl)ethyl]-9H-Purine-2,6-diamineYield 37.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of N2-butyl-8-methoxy-9H-purine-2,6-diamine trifluoroacetic acid salt (200 mg) and potassium carbonate (236 mg) in dry DMF (2 mL) were heated at 60° C. with stirring for 1 h. 2-(Tetrahydro-2H-pyran-2-yl)ethyl methanesulfonate (142 mg) was added and the reaction was continued for 3 h at 60° C. The mixture was quenched with water and extracted with EtOAc (×3). The combined organics were washed with water and brine, dried using a hydrophobic frit and evaporated to give crude material (250 mg). The material was purified by C18 reverse phase chromatography using water (containing 0.1% formic acid)-acetonitrile (containing 0.05% formic acid) as eluent (20-60%) 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 give 75 mg of material which was recrystallised from ether/light petrol yielding the title compound as a solid, 54 mg.

Workup

  1. waitthe reaction was continued for 3 h at 60° C
  2. customThe mixture was quenched with water
  3. extractionextracted with EtOAc (×3)
  4. washThe combined organics were washed with water and brine
  5. customdried
  6. customevaporated
  7. customto give crude material (250 mg)
  8. customThe material was purified by C18 reverse phase chromatography
  9. customevaporated
  10. customto remove acetonitrile
  11. extractionextracted three times with dichloromethane
  12. customthe combined extracts dried
  13. customby passing through a phase separation cartridge
  14. customthen evaporated

Sources & evidence

ORD record
ord-03cd0b3ce77a42699c9a9e7ea0099afe
Source dataset
uspto-grants-2011_07
Patent number
US07977344B2

Reaction notes

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