Bromine → 8-Bromo-2-[(2-methylpropyl)oxy]-9-(tetrahydro-2H-pyran-4-ylmethyl)-9H-purin-6-amine

HRID 1011015Notes

Reaction equation

HRID 1011015 reaction equation
[CH3:1][CH:2]([CH3:22])[CH2:3][O:4][C:5]1[N:13]=[C:12]2[C:8]([N:9]=[CH:10][N:11]2[CH2:14][CH:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[C:7]([NH2:21])[N:6]=1.C([O-])(=O)C.[Na+].[Br:28]Br>C(O)(=O)C>[Br:28][C:10]1[N:11]([CH2:14][CH:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:12]2[C:8]([N:9]=1)=[C:7]([NH2:21])[N:6]=[C:5]([O:4][CH2:3][CH:2]([CH3:22])[CH3:1])[N:13]=2

Participants

5

Reactant 3

HCID 24408BromineHCID 517045Sodium AcetateHCID 576997722-[(2-Methylpropyl)oxy]-9-(tetrahydro-2H-pyran-4-ylmethyl)-9H-Purin-6-amine

Product 1

HCID 576996388-Bromo-2-[(2-methylpropyl)oxy]-9-(tetrahydro-2H-pyran-4-ylmethyl)-9H-purin-6-amine

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

2-[(2-Methylpropyl)oxy]-9-(tetrahydro-2H-pyran-4-ylmethyl)-9H-purin-6-amine (88 mg) was dissolved in glacial acetic acid (1.5 mL) before adding sodium acetate (355 mg). The above was then cooled in an ice-bath before bromine (0.2 mL) which was added gradually. The reaction mixture was warmed to room temperature before being heated to 70° C. (external temperature) for 4 hours. The reaction mixture was quenched with 10% (w/v) sodium thiosulphate solution (to a pale yellow colour with no further change) and then the pH was adjusted to 6-7 by the addition of 2M sodium hydroxide. This was then extracted into ethyl acetate (20 mL, 3 times). The organic layer was separated, combined and dried by passing through a hydrophobic frit. The organic layer was evaporated under reduced pressure and then azeotroped with toluene to give the title compound as a pale yellow solid (0.10 g). This material then used in the next stage without the need for purification

Workup

  1. additionwas added gradually
  2. temperaturebefore being heated to 70° C. (external temperature) for 4 hours
  3. customThe reaction mixture was quenched with 10% (w/v) sodium thiosulphate solution (to a pale yellow colour with no further change) and then the pH
  4. additionwas adjusted to 6-7 by the addition of 2M sodium hydroxide
  5. extractionThis was then extracted into ethyl acetate (20 mL, 3 times)
  6. customThe organic layer was separated
  7. customdried
  8. customThe organic layer was evaporated under reduced pressure
  9. customazeotroped with toluene

Sources & evidence

ORD record
ord-42f8324766994877bc66f422b1fa9ddd
Source dataset
uspto-grants-2011_07
Patent number
US07977344B2

Reaction notes

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