反应详情

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-chloro-[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde (365 mg, 2.0 mmol), followed by borane-dimethylamine complex (118 mg, 2.0 mmol) at room temperature. The reaction was stirred for 1 hour and then was concentrated to an oil. The oil was purified by flash chromatography (50 g SiO2, 70% ethyl acetate, 6% methanol, 0.5% acetic acid, 23.5% hexanes). The resultant oil was further purified by flash 509 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 (48.6 mg, 6%). 1H NMR (400 MHz, CDCl3) δ: 1.19–1.24 (m, 2 H), 1.39–1.61 (m, 10 H), 1.83–1.87 (m, 2 H), 2.25 (t, J=8.59 Hz, 1 H), 2.38 (d, J=17.94 Hz, 1 H), 2.54 (t, J=7.71 Hz, 2 H), 2.64 (d, J=17.94 Hz, 1 H), 3.98 (d, J=5.56 Hz, 2 H), 6.71–6.77 (m, 2 H), 7.06 (t, J=7.83 Hz, 1 H), 8.66 (s, 1 H), 8.73 (s, 1 H).

1. customfollowed by borane-dimethylamine complex (118 mg, 2.0 mmol) at room temperature
2. concentrationwas concentrated to an oil
3. customThe oil was purified by flash chromatography (50 g SiO2, 70% ethyl acetate, 6% methanol, 0.5% acetic acid, 23.5% hexanes)
4. customThe resultant oil was further purified by flash 509 SiO2, 1:3->1:0 (93.5% ethyl acetate, 6% methanol, 0.5% acetic acid)