p-Toluenesulfonic acid → 4-chloro-6-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine

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Reaction Conditions

Reaction Steps

A suspension of the above 4-chloro-6-methyl-1H-pyrazolo[3,4-d]pyrimidine (325 mg, 1928 μmol) in EtOAc (3 mL) was treated with 3,4-dihydro-2H-pyran (528 μL, 5783 μmol) and MP-TsOH resin (Biotage) (72 mg, 4.3 mmol/g, 0.15 eq) and the resulting suspension was heated at 90° C. for 3 h, after which time LCMS indicated essentially complete conversion. The solution was filtered, washed with EtOAc, and concentrated to give a pale yellow oil. Purification by flash chromatography (EtOAc/hexane; 5% to 20%) gave 4-chloro-6-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine (482 mg, 98.9% yield) as a colorless oil. 1H NMR (400 MHz, d6-DMSO) δ 8.44 (s, 1H); 5.91-6.02 (m, 1H); 3.91-3.99 (m, 1H); 3.67-3.77 (m, 1H); 2.72 (s, 3H); 2.36-2.48 (m, 1H); 1.96-2.08 (m, 1H); 1.87-1.95 (m, 1H); 1.32-1.84 (m, 3H).

Provenance & Evidence