Sodium Methoxide → HCID 59252556, compound

HRID 590487Notes

Reaction equation

HRID 590487 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 Methoxide2×HCID 59252581HCID 59252581, compound

Product 1

HCID 59252556HCID 59252556, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent3×

Procedure

A solution of sodium methoxide in methanol (0.5M, 13 ml, 6.5 mmol) was added to a solution of 8-bromo-N2-[(1S)-1-methylbutyl]-9-(tetrahydro-2H-pyran-2-yl)-9H-purine-2,6-diamine (1.26 g, 3.29 mmol) in methanol (10 ml) and the resulting solution heated under reflux for 4 hours. More sodium methoxide in methanol (0.5M, 12 ml, 6 mmol) was then added and refluxing continued for a further 18 hours. The mixture was cooled and 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 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. The product-containing fractions were combined and evaporated in vacuo to give the title compound as a white foam (0.848 g).

Workup

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

Sources & evidence

ORD record
ord-7c637b2ced0d4c5d921f6aba92e4ae5f
Source dataset
uspto-grants-2016_01
Patent number
US09233962B2

Reaction notes

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