3,4-dihydro-2H-pyran → 4-Chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[4,3-c]pyridine

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Reaction Steps

p-Toluenesulfonic acid monohydrate (2.4 g, 13 mmol) and 3,4-dihydro-2H-pyran (99%, 45 mL, 520 mmol) were sequentially added to a suspension of 4-chloro-1H-pyrazolo[4,3-c]pyridine (20.0 g, 130 mmol) in dichloromethane (400 mL). The reaction mixture was allowed to stir at room temperature for 24 hours, at which time it was washed with saturated aqueous sodium bicarbonate solution. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Purification via silica gel chromatography (Eluents: 10%, then 30%, then 50% ethyl acetate in heptane) afforded the product as a white solid. Yield: 27.51 g, 115.7 mmol, 89%. LCMS m/z 238.1 [M+H+]. 1H NMR (400 MHz, CDCl3) δ 8.19 (d, J=6.0 Hz, 1H), 8.16 (d, J=0.9 Hz, 1H), 7.47 (dd, J=6.0, 0.9 Hz, 1H), 5.73 (br dd, J=9.0, 2.7 Hz, 1H), 3.97-4.04 (m, 1H), 3.72-3.80 (m, 1H), 2.43-2.53 (m, 1H), 2.07-2.20 (m, 2H), 1.65-1.85 (m, 3H).

Provenance & Evidence