1-{4-[2-(2-Cyclopentyl-4,6-dioxo-tetrahydro-pyran-2-yl)-ethyl]-2-fluoro-phenyl}-cyclopropanecarbonitrile → {4-[2-(2-Cyclopentyl-4,6-dioxo-5-[1,2,4]triazolo[1,5-a]pyrimidin-2-ylmethyl-tetrahydro-pyran-2-yl)-ethyl]-2-fluoro-phenyl}-cyclopropanecarbonitrile

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Reaction Steps

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 [1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde (296 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) to give the desired product as an oil. It was further purified by crystallization from ethyl acetate/hexanes to give a white powder (142 mg, 18%). 1H NMR (400 MHz, CDCl3) δ: 1.11-1.18 (m, 2H), 1.31-1.52 (m, 10H), 1.75-1.80 (m, 2H), 2.16 (t, J=8.84 Hz, 1H), 2.34 (d, J=17.68 Hz, 1H), 2.46 (t, J=7.83 Hz, 2H), 2.59 (d, J=17.94 Hz, 1H), 3.94 (d, J=3.79 Hz, 2H), 6.62-6.70 (m, 2H), 6.97 (t, J=7.83 Hz, 1H), 7.02-7.04 (m, 1H), 6.82-6.85 (m, 2H).

Provenance & Evidence