Sodium hydride → 4-[4-(4-Methanesulfonyl-phenoxy)-3-methyl-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isopropyl ester

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Reaction Steps

Sodium hydride (60% dispersion in mineral oil; 7 mg, 0.18 mmol) was added to a solution of 4-(methylsulfonyl)phenol (20 mg, 0.12 mmol) in dimethylformamide (1 mL) and the mixture was stirred at room temperature for 15 min. A solution of 4-(4-chloro-3-methyl-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid isopropyl ester (Intermediate 21; 40 mg, 0.12 mmol) in dimethylformamide (1 mL) was added, and the reaction mixture was allowed to stir at room temperature overnight. Saturated aqueous ammonium chloride solution was added and the mixture was extracted with ethyl acetate (3×25 mL). The organic layer was washed with water (3 times) and brine, dried (sodium sulfate), filtered, evaporated and purified on a flash silica column (20 mm×3″) eluting with 75-80% ethyl acetate/hexanes to give 4-[4-(4-methanesulfonyl-phenoxy)-3-methyl-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isopropyl ester (38 mg, 68%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 1.20 (d, 6H, J=6.3 Hz), 1.93-2.02 (m, 4H), 2.62 (s, 3H), 3.03-3.09 (m, 2H), 3.32 (s, 3H), 4.08-4.12 (m, 2H), 4.77-4.81 (m, 1H), 4.85-4.95 (m, 1H), 7.59-7.62 (m, 2H), 8.01-8.04 (m, 2H), 8.46 (s, 1H). Mass spectrum (ES) MH+=474.

Provenance & Evidence