Sodium Methoxide → HCID 59252563, compound

HRID 527823Notes

Reaction equation

HRID 527823 reaction equation
[CH3:1][O-:2].[Na+].Br[C:5]1[N:6]([CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][O:22]2)[C:7]2[C:12]([N:13]=1)=[C:11]([NH2:14])[N:10]=[C:9]([NH:15][C@H:16]([CH3:20])[CH2:17][CH2:18][CH3:19])[N:8]=2>CO>[CH3:20][C@@H:16]([NH:15][C:9]1[N:8]=[C:7]2[C:12]([N:13]=[C:5]([O:2][CH3:1])[N:6]2[CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][O:22]2)=[C:11]([NH2:14])[N:10]=1)[CH2:17][CH2:18][CH3:19]

Participants

4

Reactant 2

HCID 10942334Sodium Methoxide3×HCID 59252576HCID 59252576, compound

Product 1

HCID 59252563HCID 59252563, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent4×

Procedure

A solution of sodium methoxide in methanol (0.5M, 9 ml, 4.5 mmol) was added to a solution of 8-bromo-N2-[(1R)-1-methylbutyl]-9-(tetrahydro-2H-pyran-2-yl)-9H-purine-2,6-diamine (0.844 g, 2.20 mmol) in methanol (12 ml) and the resulting solution heated under reflux for 23.5 hours. More sodium methoxide in methanol (0.5M, 4.5 ml) was then added and refluxing continued for a further 4 hours. More sodium methoxide in methanol (0.5M, 4.5 ml) was again added and refluxing continued for a further 16.5 hours when LCMS indicated reaction to be complete. The reaction mixture was cooled to room temperature, evaporated and the residue partitioned between ethyl acetate (75 ml) and water (75 ml). The aqueous phase was re-extracted with ethyl acetate (75 ml) and the combined organic phases were washed with saturated brine, dried over anhydrous magnesium sulphate, filtered and evaporated. The residue was dissolved in dichloromethane and purified on a 100 g aminopropyl (NH2) cartridge using a 0-100% ethyl acetate in cyclohexane gradient followed by a 0-20% methanol (+1% triethylamine) gradient over 15 mins. Product-containing fractions were combined and evaporated in vacuo to give the title compound as a white foam (0.614 g).

Workup

  1. temperaturethe resulting solution heated
  2. temperatureunder reflux for 23.5 hours
  3. temperaturerefluxing
  4. temperaturerefluxing
  5. waitcontinued for a further 16.5 hours
  6. customreaction
  7. customevaporated
  8. customthe residue partitioned between ethyl acetate (75 ml) and water (75 ml)
  9. extractionThe aqueous phase was re-extracted with ethyl acetate (75 ml)
  10. washthe combined organic phases were washed with saturated brine
  11. dry with materialdried over anhydrous magnesium sulphate
  12. filtrationfiltered
  13. customevaporated
  14. dissolutionThe residue was dissolved in dichloromethane
  15. custompurified on a 100 g aminopropyl (NH2) cartridge
  16. waitfollowed by a 0-20% methanol (+1% triethylamine) gradient over 15 mins
  17. customevaporated in vacuo

Sources & evidence

ORD record
ord-eb2a194e67c446a48dad6f5db677e175
Source dataset
uspto-grants-2016_05
Patent number
US09346806B2

Reaction notes

Loading…