Tetrahydrofuran → HCID 136016229, compound
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][C:34]([CH2:36][O:37][CH2:38][C:39]5[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=5)=[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].[CH2:45]([Mg]Br)[CH3:46].O1CC[CH2:51][CH2:50]1>>[CH2:38]([O:37][CH2:36][C:34]1[S:35][C:22]2[C:21]([C:10]3[NH:11][C:12]4[C:8]([CH:9]=3)=[CH:7][CH:6]=[C:5]([C:3]([OH:4])([CH2:45][CH3:46])[CH2:50][CH3:51])[CH:13]=4)=[N:25][NH:24][C:23]=2[CH:33]=1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1Participants
4
Conditions
- Temperature
- -78 °C
Procedure
To 2-(5-benzyloxymethyl-1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-indole-1,6-dicarboxylic acid 1-tert-butyl ester 6-methyl ester [0.35 g, 0.68 mmol, Intermediate (95)] in tetrahydrofuran (5 mL) at −78° C. under nitrogen was added a 1.0M solution of ethylmagnesium bromide in tetrahydrofuran (1.7 mL, 1.7 mmol). The mixture was stirred at −78° C. for 1 hour. An additional 1.7 mL of 1.0M ethyl magnesium bromide solution was added. The temperature was raised to −45° C. and the mixture was stirred for 1 hour. It was then allowed to warm up to room temperature overnight. The reaction mixture was quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated. The residue was chromatographed through silica gel (dichloromethane/ethyl acetate, 50/50 as eluant) to produce 3-[2-(5-benzyloxymethyl-1H-thieno[3,2-c]pyrazol-3-yl)-1H-indol-6-yl]-pentan-3-ol [95 mg, 61%, Example 71] as a beige powder. LC/MS: 446.3 (M+H), RT=3.19 minutes. 1H NMR [300 Mhz, (CD3)2SO]: δ 13.18 (s, 1H), 11.44 (s, 1H), 7.50 (s, 1H), 7.45 (s, 1H), 7.43 (d, J=8.3 Hz, 1H), 7.36 (m, 5H), 7.21 (s, 1H), 6.93 (m, 1H), 6.55 (d, J=1.2 Hz, 1H), 4.78 (s, 2H), 4.59 (s, 2H), 4.43 (s, 1H), 1.75 (m, 4H), 0.66 (m, 6H).