Sodium Methoxide → 8-methoxy-2-(((S)-pentan-2-yl)oxy)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

HRID 2367962Notes

Reaction equation

Br[C:2]1[N:3]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)[C:4]2[C:9]([N:10]=1)=[C:8]([NH2:11])[N:7]=[C:6]([O:12][C@@H:13]([CH3:17])[CH2:14][CH2:15][CH3:16])[N:5]=2.[CH3:24][O-:25].[Na+]>CO>[CH3:17][C@H:13]([O:12][C:6]1[N:5]=[C:4]2[C:9]([N:10]=[C:2]([O:25][CH3:24])[N:3]2[CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)=[C:8]([NH2:11])[N:7]=1)[CH2:14][CH2:15][CH3:16]

Participants

Conditions

Temperature: 90 °C

Procedure

8-Bromo-2-{[(1S)-1-methylbutyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (for example, as prepared for Intermediate 5) (7.1 g, 18.48 mmol) was dissolved in anhydrous methanol (70 mL) and a solution of sodium methoxide (25%) in methanol (8 mL) was added dropwise under an atmosphere of nitrogen. The solution was heated to reflux at 90° C. for 4 hours under an atmosphere of nitrogen. Additional sodium methoxide in methanol (25% solution, 3 mL) was added and the reaction was stirred at 60° C. for a further 16 hours. An additional portion of sodium methoxide in methanol (25% solution, 5 mL) was added and the reaction was stirred at 90° C. for a further 7 hours. The solvent was removed on the rotary evaporator and the crude product was partitioned between ethyl acetate (75 mL) and saturated ammonium chloride solution (75 mL). The organic layer was washed with brine (75 mL). The solvent was removed on the rotary evaporator to yield the title compound as a pale orange foam (6 g).

Workup

temperatureThe solution was heated
stirringthe reaction was stirred at 90° C. for a further 7 hours
customThe solvent was removed on the rotary evaporator
customthe crude product was partitioned between ethyl acetate (75 mL) and saturated ammonium chloride solution (75 mL)
washThe organic layer was washed with brine (75 mL)
customThe solvent was removed on the rotary evaporator

Sources & evidence

ORD record: ord-11ee918358a34d52943af91d219d02de
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08703754B2

Reaction notes

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