Water → 1-phenyl-1-[2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-indol-5-yl]-ethanol

HRID 2078692Notes

Reaction equation

HRID 2078692 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17](=[O:24])[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:25]1[C:26]2[S:39][CH:38]=[CH:37][C:27]=2[N:28](C(OC(C)(C)C)=O)[N:29]=1)=O)(C)(C)C.[CH3:40][Mg]Br.O>O1CCCC1>[C:18]1([C:17]([C:13]2[CH:12]=[C:11]3[C:16](=[CH:15][CH:14]=2)[NH:8][C:9]([C:25]2[C:26]4[S:39][CH:38]=[CH:37][C:27]=4[NH:28][N:29]=2)=[CH:10]3)([OH:24])[CH3:40])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 962WaterHCID 576374025-benzoyl-2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-indole-1-carboxylic acid tert-butyl ester2×HCID 178418573HCID 178418573, compound2×

Product 1

HCID 1355182791-phenyl-1-[2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-indol-5-yl]-ethanolYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-benzoyl-2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-indole-1-carboxylic acid tert-butyl ester [Intermediate (13)] in anhydrous tetrahydrofuran (5 mL) is added methylmagnesium bromide (1M in tetrahydrofuran, 0.8 mL) at −78° C. Stirred under nitrogen for 30 minutes. Added another 0.88 mL of methylmagnesium bromide and let the reaction warm to room temperature slowly. After overnight water/saturated ammonium chloride (2 mL) is added at 0° C. and extracted twice with ethyl acetate (25 mL). The combined ethyl acetate phases are washed with brine and dried over sodium sulfate. The residue is chromatographed on 10 g silica gel, eluting with 30 to 50% ethyl acetate gradient in heptane to afford 1-phenyl-1-[2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-indol-5-yl]-ethanol (56 mg, 71%, Example 26) as a beige solid; LC/MS: 360 (M+H); 1H NMR [(CD3)2SO)]: δ 13.20 (1H, s), 11.45 (1H, s), 7.73 (1H, d), 7.62 (1H, s), 7.43 (2H, m), 7.25 (6H, m), 6.59 (1H, s), 5.53 (1H, s), 1.86 (3H, s).

Workup

  1. extractionextracted twice with ethyl acetate (25 mL)
  2. washThe combined ethyl acetate phases are washed with brine
  3. dry with materialdried over sodium sulfate
  4. customThe residue is chromatographed on 10 g silica gel
  5. washeluting with 30 to 50% ethyl acetate gradient in heptane

Sources & evidence

ORD record
ord-7207e7a0394940efbe2a683d2cdf8ee5
Source dataset
uspto-grants-2011_04
Patent number
US07928231B2

Reaction notes

Loading…