反应详情

温度

-10 °C

A solution of 1-{4-[2-(2-cyclopentyl-4,6-dioxo-tetrahydro-pyran-2-yl)-ethyl]-2-fluoro-phenyl}-cyclopropanecarbonitrile (568 mg, 1.54 mmol) in anhydrous MeOH (6.0 mL) was treated with 6-methyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde (324 mg, 2.0 mmol), followed by borane-dimethylamine complex (118 mg, 2.0 mmol) at room temperature. The reaction was stirred for 1 hour before it was cooled to −10° C. for 2 hours. The precipitate was removed by filtration, and the filtrate was concentrated to an oil. The oil was purified by flash chromatography (50 g SiO2, 1:3->1:0 (93.5% ethyl acetate, 6% methanol, 0.5% acetic acid): (81.5% hexanes, 12% ethyl acetate, 6% methanol, 0.5% acetic acid)) to give the desired product as an oil. It was further purified by crystallization from ethyl acetate/hexanes to give a white powder (146 mg, 18%). 1H NMR (400 MHz, CDCl3) δ: 1.41–1.64 (m, 8 H), 1.84–1.88 (m, 2 H), 2.22–2.28 (m, 2 H), 2.42 (s, 3 H), 2.49–2.59 (m, 4 H), 2.65–2.74 (m, 3 H), 3.97–4.05 (m, 2 H), 6.72–6.82 (m, 2 H), 7.05–7.10 (m, 1 H), 8.55 (s, 1 H), 8.67 (s, 1 H).

1. customfollowed by borane-dimethylamine complex (118 mg, 2.0 mmol) at room temperature
2. customThe precipitate was removed by filtration
3. concentrationthe filtrate was concentrated to an oil
4. customThe oil was purified by flash chromatography (50 g SiO2, 1:3->1:0 (93.5% ethyl acetate, 6% methanol, 0.5% acetic acid): (81.5% hexanes, 12% ethyl acetate, 6% methanol, 0.5% acetic acid))