9-Ethyl-9H-carbazole-2-carbaldehyde → 2-((3-(1H-pyrazol-5-yl)piperidin-1-yl)methyl)-9-ethyl-9H-carbazole

Participants

Reaction Steps

A 100-mL 3-necked round-bottom flask was charged with a solution of 9-ethyl-9H-carbazole-2-carbaldehyde (1.12 g, 5.02 mmol, 1.00 equiv) in THF (50 mL). To this was added 3-(1H-pyrazol-5-yl)piperidine hydrochloride (940 mg, 5.01 mmol, 1.00 equiv), Ti(OiPr)4 (2 g, 7.04 mmol, 1.40 equiv) and TEA (660 mg, 6.52 mmol, 1.30 equiv). The resulting solution was stirred at room temperature overnight. To the mixture was then added NaBH3CN (1.26 mg, 0.02 mmol, 4.00 equiv). The resulting solution was stirred at room temperature for 4 hours. Upon completion, the reaction was then quenched by the addition of water (50 mL). The resulting solution was extracted with ethyl acetate (4×50 mL) and the combined organic layers were dried over anhydrous magnesium sulfate and concentrated on a rotary evaporator. The residue was purified by silica gel column chromatography eluted with ethyl acetate/petroleum ether (1:10) affording 2-((3-(1H-pyrazol-5-yl)piperidin-1-yl)methyl)-9-ethyl-9H-carbazole as a white solid (0.3 g, 17%). LCMS:[M+H]+ 359. 1H NMR (CDCl3, 300 MHz) δ 8.08 (t, 2H), 7.50-7.41 (m, 4H), 7.28-7.21 (m, 2H), 6.05 (d, 1H), 4.40 (q, 2H), 3.80 (q, 2H), 3.16 (s, 1H), 2.72 (br, 4H), 1.88 (s, 1H), 1.65 (d, 3H), 1.46 (t, 3H).

Provenance & Evidence