Sodium Methoxide → (3-((6-amino-8-methoxy-2-(2-methoxyethoxy)-9H-purin-9-yl)methyl)phenyl)methanol

HRID 2197451Notes

Reaction equation

[NH2:1][C:2]1[N:10]=[C:9]([O:11][CH2:12][CH2:13][O:14][CH3:15])[N:8]=[C:7]2[C:3]=1[N:4]=[C:5](Br)[N:6]2[CH2:16][C:17]1[CH:18]=[C:19]([CH2:23][OH:24])[CH:20]=[CH:21][CH:22]=1.[CH3:26][O-:27].[Na+]>CO>[NH2:1][C:2]1[N:10]=[C:9]([O:11][CH2:12][CH2:13][O:14][CH3:15])[N:8]=[C:7]2[C:3]=1[N:4]=[C:5]([O:27][CH3:26])[N:6]2[CH2:16][C:17]1[CH:18]=[C:19]([CH2:23][OH:24])[CH:20]=[CH:21][CH:22]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of Compound (6) (1.53 g, 3.74 mmol) in methanol (40 mL) was slowly added sodium methoxide (4.04 g, 74.85 mmol). The reaction mixture was heated to 70° C. for 5 hours, at which time Dowex (H+) resin was added to quench any remaining methoxide. The resin was filtered off and the solvent was evaporated. Salts were removed by partition between water and dichloromethane, and the combined organic layers were dried over magnesium sulfate and evaporated to dryness giving 1.03 g (76%) of Compound (7) as a white solid, which was used in the next step without further purification. 1H NMR (300 MHz, CDCl3) δ 3.39 (s, 3H), 3.73 (t, J=4.8, 9.6 Hz, 2H), 4.12 (s, 3H), 4.45 (t, J=4.5, 9.3 Hz, 2H), 4.56 (s, 2H), 5.12 (s, 2H), 7.28 (m, 4H). LCMS: m/z for C17H21N5O4++H observed 360.1 at 1.87 minutes of a 3.5 minute run, eluting 5-95% CH3CN in H2O (C18 column).

Workup

additionwas added
customto quench any remaining methoxide
filtrationThe resin was filtered off
customthe solvent was evaporated
customSalts were removed
customby partition between water and dichloromethane
dry with materialthe combined organic layers were dried over magnesium sulfate
customevaporated to dryness

Sources & evidence

ORD record: ord-68ae6a633f5e41f0a9b0aa00d315edce
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08338593B2

Reaction notes

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