Sodium Methoxide → 8-(Methyloxy)-2-{[(1S)-1-methylpentyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

HRID 590458Notes

Reaction equation

HRID 590458 reaction equation
[CH3:1][O-:2].[Na+].Br[C:5]1[N:6]([CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)[C:7]2[C:12]([N:13]=1)=[C:11]([NH2:14])[N:10]=[C:9]([O:15][C@@H:16]([CH3:21])[CH2:17][CH2:18][CH2:19][CH3:20])[N:8]=2>CO>[CH3:1][O:2][C:5]1[N:6]([CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)[C:7]2[C:12]([N:13]=1)=[C:11]([NH2:14])[N:10]=[C:9]([O:15][C@@H:16]([CH3:21])[CH2:17][CH2:18][CH2:19][CH3:20])[N:8]=2

Participants

4

Reactant 2

HCID 10942334Sodium Methoxide2×HCID 592526088-Bromo-2-{[(1S)-1-methylpentyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

Product 1

HCID 592525538-(Methyloxy)-2-{[(1S)-1-methylpentyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent3×

Procedure

A solution of sodium methoxide in methanol (0.5M, 20 ml, 10 mmol) was added to a solution of 8-bromo-2-{[(1S)-1-methylpentyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (2.368 g, 5.95 mmol) in methanol (10 ml) and the mixture heated under reflux for 5 hours. More sodium methoxide in methanol (4 ml, 2 mmol) was added and the mixture refluxed for a further 2 hours and then cooled and evaporated. The residue was partitioned between ethyl acetate (100 ml) and water (100 ml). The organic phase was separated, washed with saturated brine, dried over anhydrous magnesium sulphate, filtered and evaporated. The residue was dissolved in dichloromethane and purified on an aminopropyl (NH2) cartridge (100 g) using a 0-100% ethyl acetate in cyclohexane gradient over 40 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white foam (1.725 g).

Workup

  1. temperaturethe mixture heated
  2. temperatureunder reflux for 5 hours
  3. temperaturethe mixture refluxed for a further 2 hours
  4. temperaturecooled
  5. customevaporated
  6. customThe residue was partitioned between ethyl acetate (100 ml) and water (100 ml)
  7. customThe organic phase was separated
  8. washwashed with saturated brine
  9. dry with materialdried over anhydrous magnesium sulphate
  10. filtrationfiltered
  11. customevaporated
  12. dissolutionThe residue was dissolved in dichloromethane
  13. custompurified on an aminopropyl (NH2) cartridge (100 g)
  14. customover 40 mins
  15. customevaporated in vacuo

Sources & evidence

ORD record
ord-8485d5c227734d92a87d69792f704561
Source dataset
uspto-grants-2016_01
Patent number
US09233962B2

Reaction notes

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