N-bromobutanimide → 8-bromo-2-(((S)-pentan-2-yl)oxy)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine
Reaction equation
[Br:1]N1C(=O)CCC1=O.[CH3:9][C@H:10]([O:14][C:15]1[N:23]=[C:22]2[C:18]([N:19]=[CH:20][N:21]2[CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][O:25]2)=[C:17]([NH2:30])[N:16]=1)[CH2:11][CH2:12][CH3:13]>C(Cl)(Cl)Cl>[Br:1][C:20]1[N:21]([CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][O:25]2)[C:22]2[C:18]([N:19]=1)=[C:17]([NH2:30])[N:16]=[C:15]([O:14][C@@H:10]([CH3:9])[CH2:11][CH2:12][CH3:13])[N:23]=2Participants
Procedure
N-Bromosuccinimide (12.16 g, 68.3 mmol) was added portionwise over 5 minutes to a stirred solution of 2-{[(1S)-1-methylbutyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (14.9 g, 48.8 mmol) (for example, as prepared for Intermediate 4) in chloroform (80 mL) at <5° C. under an atmosphere of nitrogen. The reaction mixture was stirred at <5° C. for 5 hours then washed with saturated sodium hydrogen carbonate solution (80 mL) then water (80 mL). The foam was dissolved in dichloromethane (50 mL) and washed with water (50 mL) then brine (50 mL). The combined aqueous phases were washed with dichloromethane (50 mL). The combined organic layers were dried through a hydrophobic frit, and the solvent removed in vacuo to yield the title compound as an orange foam (18.5 g).
Workup
- washthen washed with saturated sodium hydrogen carbonate solution (80 mL)
- dissolutionThe foam was dissolved in dichloromethane (50 mL)
- washwashed with water (50 mL)
- washThe combined aqueous phases were washed with dichloromethane (50 mL)
- customThe combined organic layers were dried through a hydrophobic frit
- customthe solvent removed in vacuo
Sources & evidence
- ORD record
- ord-bd4ef91b1baa46b19e23190e3c817026
- Source dataset
- uspto-grants-2014_04
- Patent number
- US08703754B2
Reaction notes
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