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

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Reaction Steps

Sodium hydride (60% dispersion in mineral oil; 82 mg, 2.1 mmol) was added to a solution of 4-(methylsulfonyl)phenol (281 mg, 1.6 mmol) in dimethylformamide (9 mL) and the mixture was stirred at room temperature for 20 min. A solution of 4-(4-chloro-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylic acid tert-butyl ester (Intermediate 19; 551 mg, 1.6 mmol) in dimethylformamide (5 mL) was added, and the reaction mixture was stirred at room temperature for 3.5 h. Saturated aqueous ammonium chloride solution was added and the mixture was extracted with ethyl acetate (3×90 mL). The organic layer was washed with water (3 times) and brine, dried (sodium sulfate), filtered, evaporated and purified on a flash silica column (40 mm×4″) eluting with 66-75% ethyl acetate/hexanes to give 4-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (400 mg, 52%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 1.41 (s, 9H), 1.92-2.02 (m, 4H), 2.94-3.05 (m, 2H), 3.28-3.30 (m, methyl sulfone and water peak), 4.04-4.12 (m, 2H), 4.94-5.06 (m, 1H), 7.59-7.64 (m, 2H), 8.01-8.06 (m, 2H), 8.37 (s, 1H), 8.54 (s, 1H). Mass spectrum (ES) MH+=474.

Provenance & Evidence