Potassium Carbonate → 9-(4-Chlorobutyl)-2-{[(1S)-1-methylbutyl]oxy}-8-(methyloxy)-9H-purin-6-amine
Reaction equation
[CH3:1][C@H:2]([O:6][C:7]1[NH:8][C:9]([NH2:18])=[C:10]2[C:14]([N:15]=1)=[N:13][C:12]([O:16][CH3:17])=[N:11]2)[CH2:3][CH2:4][CH3:5].C(=O)([O-])[O-].[K+].[K+].Br[CH2:26][CH2:27][CH2:28][CH2:29][Cl:30]>CN(C=O)C>[Cl:30][CH2:29][CH2:28][CH2:27][CH2:26][N:13]1[C:12]([O:16][CH3:17])=[N:11][C:10]2[C:14]1=[N:15][C:7]([O:6][C@@H:2]([CH3:1])[CH2:3][CH2:4][CH3:5])=[N:8][C:9]=2[NH2:18]Participants
Conditions
- Temperature
- 50 °C
Procedure
2-{[(1S)-1-methylbutyl]oxy}-8-(methyloxy)-1H-purin-6-amine (1 g, 2.74 mmol) and potassium carbonate (0.946 g, 6.84 mmol) in DMF (12.5 ml) were stirred under nitrogen and heated to 50° C. for 1 hour. The mixture was then allowed to cool to ambient temperature and 1-bromo-4-chlorobutane (0.315 ml, 2.74 mmol) was added and stirring was continued under nitrogen at ambient temperature overnight. The mixture was then partitioned between ethyl acetate and water. The aqueous layer was washed with ethyl acetate and the combined organic extracts were washed with saturated brine and passed through a hydrophobic frit and evaporated in vacuo. The residue (1.0322 g) was dissolved in dichloromethane and loaded onto an amino cartridge (70 g) and eluted using a 0-100% ethyl acetate in cyclohexane gradient over 40 minutes. Product fractions were combined and evaporated to give the title compound as an off-white solid (667 mg).
Workup
- temperatureto cool to ambient temperature
- customThe mixture was then partitioned between ethyl acetate and water
- washThe aqueous layer was washed with ethyl acetate
- washthe combined organic extracts were washed with saturated brine
- customevaporated in vacuo
- dissolutionThe residue (1.0322 g) was dissolved in dichloromethane
- washeluted
- customover 40 minutes
- customevaporated
Sources & evidence
- ORD record
- ord-038372330ded4009be6cd474d7dadba2
- Source dataset
- uspto-grants-2013_11
- Patent number
- US08575181B2
Reaction notes
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