N-bromobutanimide → 8-Bromo-2-[(1-methylethyl)oxy]-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine
Reaction equation
[Br:1]N1C(=O)CCC1=O.[CH3:9][CH:10]([O:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[CH:18][N:19]2[CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)=[C:15]([NH2:28])[N:14]=1)[CH3:11]>C(Cl)(Cl)Cl>[Br:1][C:18]1[N:19]([CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)[C:20]2[C:16]([N:17]=1)=[C:15]([NH2:28])[N:14]=[C:13]([O:12][CH:10]([CH3:9])[CH3:11])[N:21]=2Participants
Conditions
- Temperature
- 2.5 °C
Procedure
N-Bromosuccinimide (604 mg, 3.39 mmol) was added to a solution of 2-[(1-methylethyl)oxy]-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (888 mg, 3.20 mmol) in chloroform (30 ml) at 0-5° C. under nitrogen. The mixture was stirred at 0-5° C. for 1 hour during which time it became reddish brown in colour and it was then warmed to room temperature and stirred for a further 4 hours. LCMS indicated the reaction to be incomplete and more N-bromosuccinimide (114 mg, 0.641 mmol) was added and the reaction mixture stirred at room temperature overnight. The reaction mixture was then diluted with chloroform (30 ml), washed with water (2×20 ml) and the layers were separated using a hydrophobic frit and the organic layer was evaporated to give a red solid (1.16 g). This material was dissolved in dichloromethane and purified by silica gel chromatography on an SPE cartridge (50 g) using a 0-100% ethyl acetate in cyclohexane gradient as eluent. The appropriate fractions were combined and evaporated to give the title compound as a pale yellow solid 712 mg.
Workup
- temperaturewas then warmed to room temperature
- stirringstirred for a further 4 hours
- customthe reaction
- stirringthe reaction mixture stirred at room temperature overnight
- washwashed with water (2×20 ml)
- customthe layers were separated
- customthe organic layer was evaporated
Sources & evidence
- ORD record
- ord-e8b2f13cf10843e1a86aab980895fead
- Source dataset
- uspto-grants-2016_01
- Patent number
- US09233962B2
Reaction notes
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