Water → 1,1,1-trifluoro-3-(4-((4-(6-fluoro-1-(phenylsulfonyl)-1H-indol-3-yl)-1H-pyrazol-1-yl)methyl)piperidin-1-yl)propan-2-ol

HRID 2274820Notes

Reaction equation

HRID 2274820 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20]3[CH:21]=[N:22][N:23]([CH2:25][CH:26]4[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]4)[CH:24]=3)=[CH:7][N:8]2[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[F:38][C:39]([F:44])([F:43])[CH:40]1[CH2:42][O:41]1.O>CN(C=O)C>[F:38][C:39]([F:44])([F:43])[CH:40]([OH:41])[CH2:42][N:29]1[CH2:30][CH2:31][CH:26]([CH2:25][N:23]2[CH:24]=[C:20]([C:6]3[C:5]4[C:9](=[CH:10][C:2]([F:1])=[CH:3][CH:4]=4)[N:8]([S:11]([C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=4)(=[O:12])=[O:13])[CH:7]=3)[CH:21]=[N:22]2)[CH2:27][CH2:28]1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 5207692-(Trifluoromethyl)oxiraneHCID 1180606356-fluoro-1-(phenylsulfonyl)-3-(1-(piperidin-4-ylmethyl)-1H-pyrazol-4-yl)-1H-indole2×

Product 1

HCID 1180606111,1,1-trifluoro-3-(4-((4-(6-fluoro-1-(phenylsulfonyl)-1H-indol-3-yl)-1H-pyrazol-1-yl)methyl)piperidin-1-yl)propan-2-olYield 47.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 6-fluoro-1-(phenylsulfonyl)-3-(1-(piperidin-4-ylmethyl)-1H-pyrazol-4-yl)-1H-indole (Intermediate 21; 111 mg; 0.25 mmol), K2CO3 (35 mg; 0.25 mmol) and 2-(trifluoromethyl)oxirane (142 mg; 1.27 mmol) in DMF (10 mL) was stirred overnight under nitrogen. The reaction mixture was added water (20 mL) and extracted with EtOAc (50 mL×2). The combined organic layers were dried over anhydrous Na2SO4, filtered, concentrated, and purified by reverse phase flash chromatograph to afford 65 mg (47%) of the title compound as a yellow solid.

Workup

  1. extractionextracted with EtOAc (50 mL×2)
  2. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by reverse phase flash chromatograph

Sources & evidence

ORD record
ord-cc7ef0185e574a8795aa3db54d1dd165
Source dataset
uspto-grants-2015_09
Patent number
US09126984B2

Reaction notes

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