Tetrahydrofuran → 3-[2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-indol-6-yl]-pentan-3-ol
Reaction equation
CO[C:3]([C:5]1[CH:13]=[C:12]2[C:8]([CH:9]=[C:10]([C:21]3[C:22]4[S:35][CH:34]=[CH:33][C:23]=4[N:24](C(OC(C)(C)C)=O)[N:25]=3)[N:11]2C(OC(C)(C)C)=O)=[CH:7][CH:6]=1)=[O:4].[CH2:36]([Mg]Br)[CH3:37].O1CC[CH2:42][CH2:41]1>>[NH:24]1[C:23]2[CH:33]=[CH:34][S:35][C:22]=2[C:21]([C:10]2[NH:11][C:12]3[C:8]([CH:9]=2)=[CH:7][CH:6]=[C:5]([C:3]([OH:4])([CH2:36][CH3:37])[CH2:41][CH3:42])[CH:13]=3)=[N:25]1Participants
4
Reactant 3
Product 1
Procedure
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).