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

HRID 590457Notes

Reaction equation

HRID 590457 reaction equation
[Br:1]N1C(=O)CCC1=O.[CH3:9][C@H:10]([O:15][C:16]1[N:24]=[C:23]2[C:19]([N:20]=[CH:21][N:22]2[CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)=[C:18]([NH2:31])[N:17]=1)[CH2:11][CH2:12][CH2:13][CH3:14].O>C(Cl)(Cl)Cl>[Br:1][C:21]1[N:22]([CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)[C:23]2[C:19]([N:20]=1)=[C:18]([NH2:31])[N:17]=[C:16]([O:15][C@@H:10]([CH3:9])[CH2:11][CH2:12][CH2:13][CH3:14])[N:24]=2

Participants

5

Reactant 3

HCID 962WaterHCID 67184N-bromobutanimide2×HCID 592526582-{[(1S)-1-Methylpentyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

Product 1

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

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

N-Bromosuccinimide (1.504 g, 8.45 mmol) was added portionwise to a stirred solution of 2-{[(1S)-1-methylpentyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (2.453 g, 7.68 mmol) in chloroform (40 ml) under at atmosphere of nitrogen cooled in an ice-bath. After 3 hours LCMS indicated the reaction to be 80% complete and more N-bromosuccinimide (0.68 g) was added and stirring continued for a further 2 hours. Water (40 ml) was added and the phases separated using a hydrophobic frit. The organic phase was evaporated and the residue dissolved in dichloromethane and purified on an aminopropyl (NH2) cartridge (100 g) using a 0-100% ethyl acetate in cyclohexane gradient followed by a 0-20% methanol (+1% triethylamine) gradient over 60 mins. The appropriate fractions were combined and evaporated in vacuo to the title compound as a white foam (2.38 g).

Workup

  1. temperaturecooled in an ice-bath
  2. customthe reaction
  3. waitcontinued for a further 2 hours
  4. customthe phases separated
  5. customThe organic phase was evaporated
  6. dissolutionthe residue dissolved in dichloromethane
  7. custompurified on an aminopropyl (NH2) cartridge (100 g)
  8. waitfollowed by a 0-20% methanol (+1% triethylamine) gradient over 60 mins
  9. customevaporated in vacuo to the title compound as a white foam (2.38 g)

Sources & evidence

ORD record
ord-dc6857b47be04ae080504f7af118a367
Source dataset
uspto-grants-2016_01
Patent number
US09233962B2

Reaction notes

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