Neoheptanol → 2-[(2,2-Dimethylpentyl)oxy]-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine
Reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[C:4]([NH2:17])[N:3]=1.[CH3:18][C:19]([CH3:25])([CH2:22][CH2:23][CH3:24])[CH2:20][OH:21].[H-].[Na+]>>[CH3:18][C:19]([CH3:25])([CH2:22][CH2:23][CH3:24])[CH2:20][O:21][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[C:4]([NH2:17])[N:3]=1Participants
Conditions
- Temperature
- 50 °C
Procedure
To a suspension of 2-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (500 mg) and 2,2-dimethylpentanol (3.8 mL) at 50° C. was added sodium hydride (396 mg, 60% dispersion) in portions. To the resultant viscous foam was added a further portion of 2,2-dimethylpentanol (1.5 mL). The reaction was stirred at 50° C. for 72 h. The reaction mixture was cooled then carefully quenched with water (10 mL) and extracted with EtOAc (3×25 mL). The organics were combined, washed with brine (30 mL), dried over MgSO4, filtered and concentrated in vacuo to give a yellow oil. This was azeotroped with toluene (×3) and the resulting viscous yellow oil was purified by C18 reverse phase chromatography (ISCO) using water (0.1% formic acid)-acetonitrile (0.05% formic acid) as eluent (30-80%) to afford the title compound as a brown solid (372 mg).
Workup
- temperatureThe reaction mixture was cooled
- customthen carefully quenched with water (10 mL)
- extractionextracted with EtOAc (3×25 mL)
- washwashed with brine (30 mL)
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- customto give a yellow oil
- customThis was azeotroped with toluene (×3)
- customthe resulting viscous yellow oil was purified by C18 reverse phase chromatography (ISCO)
Sources & evidence
- ORD record
- ord-79a982ac5d544a26a36d3294f63825d6
- Source dataset
- uspto-grants-2011_07
- Patent number
- US07977344B2
Reaction notes
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