3,4-dihydro-2H-pyran → 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carbaldehyde

Participants

Reaction Steps

A solution of 5-bromo-1H-indazole-3-carbaldehyde (1.00 g, 4.44 mmol), dihydropyran (912 uL, 10.0 mmol), and p-toluenesulfonic acid monohydrate (16.9 mg, 0.0889 mmol) in DCM (8.8 mL) was stirred at room temperature for 24 h. The reaction was poured into saturated aqueous sodium bicarbonate (10 mL) and extracted with dichloromethane (3×5 mL). The combined organic fractions were washed with saturated aqueous sodium chloride (1×10 mL), dried over sodium sulfate, filtered, and concentrated. Purification by ISCO chromatography (10 to 40% ethyl acetate:heptane) afforded 858 mg (56%) of the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.17 (s, 1 H), 8.28 (d, J=1.8 Hz, 1 H), 7.92 (d, J=8.3 Hz, 1 H), 7.80-7.61 (m, 1 H), 6.08 (dd, J=2.5, 9.3 Hz, 1 H), 3.99-3.69 (m, 2 H), 2.46-2.26 (m, 1 H), 2.17-1.92 (m, 2 H), 1.87-1.67 (m, 1 H), 1.68-1.53 (m, 2 H); MS (ESI): 309.03, 311.05 [M+H]+; HPLC tR=3.38 min (ZQ3, nonpolar—4 min).

Provenance & Evidence