N-bromobutanimide → 8-Bromo-2-{[(1R)-1-methylbutyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

HRID 1011073Notes

Reaction equation

HRID 1011073 reaction equation
[CH3:1][C@@H:2]([O:6][C:7]1[N:15]=[C:14]2[C:10]([N:11]=[CH:12][N:13]2[CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)=[C:9]([NH2:22])[N:8]=1)[CH2:3][CH2:4][CH3:5].[Br:23]N1C(=O)CCC1=O>C(Cl)(Cl)Cl.ClCCl>[Br:23][C:12]1[N:13]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)[C:14]2[C:10]([N:11]=1)=[C:9]([NH2:22])[N:8]=[C:7]([O:6][C@H:2]([CH3:1])[CH2:3][CH2:4][CH3:5])[N:15]=2

Participants

5

Reactant 2

HCID 67184N-bromobutanimideHCID 576997952-{[(1R)-1-Methylbutyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

Product 1

HCID 576998388-Bromo-2-{[(1R)-1-methylbutyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amineYield 82.3%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

2-{[(1R)-1-methylbutyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (5.05 g, 16.54 mmol) was dissolved in chloroform (30 ml) and cooled to 0° C. To this solution N-bromosuccinimide (3.24 g, 18.19 mmol) was added portionwise keeping the temperature below 2° C. This gave a dark green solution which was stirred at 0° C. for 30 minutes before allowing to warm to room temperature and stirring for 6 hours. The reaction mixture was washed with water (2×50 ml) and the layers separated using hydrophobic frit. The organic layer was concentrated to give a dark brown gum which was dissolved in dichloromethane and purified by chromatography silica (100 g) using a 0-50% gradient of ethyl acetate-cyclohexane over 60 mins on a Flashmaster II. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a yellow foam (5.23 g).

Workup

  1. customthe temperature below 2° C
  2. customThis gave a dark green solution which
  3. temperatureto warm to room temperature
  4. stirringstirring for 6 hours
  5. washThe reaction mixture was washed with water (2×50 ml)
  6. customthe layers separated
  7. concentrationThe organic layer was concentrated
  8. customto give a dark brown gum which
  9. custompurified by chromatography silica (100 g)
  10. customover 60 mins
  11. customevaporated in vacuo

Sources & evidence

ORD record
ord-e85d3f6633ef48caa293e0c4fbb45eac
Source dataset
uspto-grants-2011_07
Patent number
US07977344B2

Reaction notes

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