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

Participants

Reaction Steps

To 2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-indole-1,6-dicarboxylic acid 1-tert-butyl ester 6-methyl ester [250 mg, 0.5 mmol, Intermediate (36)] in tetrahydrofuran (5 mL) was added a 1.0M solution of ethyl magnesium bromide in tetrahydrofuran (2.5 mL, 2.5 mmol) at −45° C. under nitrogen. The mixture was allowed to warm up and stirred at room temperature for 3 hours. An additional 2 mL of 1.0M ethyl magnesium bromide solution was added. The resulting solution was stirred at room temperature overnight. It was then quenched with a mixture of brine and saturated ammonium chloride and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated. The residue was chromatographed through silica gel (n-heptane/ethyl acetate, 50/50 as eluant) to produce 3-[2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-indol-6-yl]-pentan-3-ol [137 mg, 92%, Example 70] as a white powder. LC/MS: 326.2 (M+H), RT=3.07 minutes; 1H NMR [300 Mhz, (CD3)2SO]: δ 13.18 (s, 1H), 11.43 (s, 1H), 7.73 (d, J=5.2 Hz, 1H), 7.50 (s, 1H), 7.44 (d, J=8.2 Hz, 1H), 7.18 (d, J=5.2 Hz, 1H), 6.94 (dd, J1=1.1 Hz, J2=8.4 Hz, 1H), 6.56 (d, J=1.5 Hz, 1H), 4.41 (s, 1H), 1.76 (m, 4H), 0.66 (t, j=6.2 Hz, 6H).

Provenance & Evidence