Tetrahydrofuran → Dicyclopropyl-[2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-indol-6-yl]-methanol

Participants

Reaction Steps

To a mixture of 2-(1H-Thieno[3,2-c]pyrazol-3-yl)-1H-indole-6-carboxylic acid methyl ester (180 mg, 0.605 mmol, Example 43) in anhydrous tetrahydrofuran (8 mL) is added cyclopropylmagnesium bromide (6.0 mL, 0.5 M in tetrahydrofuran) at 0° C. The ice bath is removed and the reaction mixture stirred at room temperature for 4 hours. To it is added an additional cyclopropylmagnesium bromide (6 mL, 0.5 M in tetrahydrofuran) and stirred at room temperature overnight. The reaction is not completed (TLC) and added cyclopropylmagnesium bromide (6.0 mL). The solublized reaction mixture is then stirred overnight. The reaction is quenched at 0° C. by the addition of saturated ammonium chloride. The reaction mixture is partitioned between diethyl ether and water. The diethyl ether layer is washed with brined and dried over magnesium sulfate. The crude is chromatographed on 10 g silica gel cartridge (30-50% ethyl acetate gradient in heptane) to afford product (120 mg). The product is recrystallized as follows: In a Smith vial, a mixture of solid (120 mg) and ethyl acetate (2 mL) is heated at 70° C. using microwave (Personal chemistry optimizer) for 240 seconds at normal absorption. Upon cooling dicyclopropyl-[2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-indol-6-yl]-methanol crystallized as a white solid. mp 110-112° C.; 1H NMR [(CD3)2SO)]: δ 13.189 (1H, s), 11.440 (1H, s), 7.747 (1H, d, J=5.1 Hz), 7.631 (1H, s), 7.467 (1H, d, J=8.4 Hz), 7.249 (2H, m), 6.579 (1H, s), 4.304 (1H, s), 1.225 (2H), 0.581 (2H, m), 0.387 (4H, m), 0.195 (2H, m); LC/MS: 350 (M+H).

Provenance & Evidence