Potassium Carbonate → N2-Butyl-9-[(2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl]-8-methoxy-9H-purine-2,6-diamine

HRID 1010989Notes

Reaction equation

HRID 1010989 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][CH:37]1[CH2:42][CH2:41][O:40][C:39]([CH3:44])([CH3:43])[CH2:38]1)(=O)=O.[Br-].[Li+]>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][CH:37]2[CH2:42][CH2:41][O:40][C:39]([CH3:44])([CH3:43])[CH2:38]2)=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 82050Lithium BromideHCID 57699693(2,2-Dimethyltetrahydro-2H-pyran-4-yl)methyl methanesulfonateHCID 178448879HCID 178448879, compound

Product 1

HCID 57699692N2-Butyl-9-[(2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl]-8-methoxy-9H-purine-2,6-diamineYield 36.2%

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. under nitrogen with stirring for 1 h. (2,2-Dimethyltetrahydro-2H-pyran-4-yl)methyl methanesulfonate (152 mg) was added and stirring was continued for 5 h at 50° C. The reaction was cooled to room temperature and stirred for 16 h. Lithium bromide (50 mg) was added and heating was continued for 5 h at 50° C., then 8 h at 90° 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 (210 mg). This was purified by C18 reverse phase chromatography (ISCO) using water (0.1% formic acid)-acetonitrile (0.05% formic acid) as eluent (20-60%) to give the title compound (75 mg).

Workup

  1. additionwas added
  2. temperatureThe reaction was cooled to room temperature
  3. stirringstirred for 16 h
  4. temperatureheating
  5. waitwas continued for 5 h at 50° C.
  6. custom8 h
  7. customat 90° C
  8. customThe mixture was quenched with water
  9. extractionextracted with EtOAc (×3)
  10. washThe combined organics were washed with water and brine
  11. customdried
  12. customevaporated
  13. customto give crude material (210 mg)
  14. customThis was purified by C18 reverse phase chromatography (ISCO)

Sources & evidence

ORD record
ord-65944a1b126141288cea51ab8e8f8cb4
Source dataset
uspto-grants-2011_07
Patent number
US07977344B2

Reaction notes

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