Indole → N-{3-[4-(1H-indol-1-ylmethyl)phenyl]pyrazin-2-yl}-2-(trifluoromethyl)benzenesulfonamide

HRID 2401033Notes

Reaction equation

HRID 2401033 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[H-].[Na+].[H][H].Cl[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[C:23]([NH:28][S:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[C:38]([F:41])([F:40])[F:39])(=[O:31])=[O:30])=[N:24][CH:25]=[CH:26][N:27]=2)=[CH:18][CH:17]=1>CN(C)C=O.O>[N:1]1([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[C:23]([NH:28][S:29]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=4[C:38]([F:40])([F:39])[F:41])(=[O:30])=[O:31])=[N:24][CH:25]=[CH:26][N:27]=3)=[CH:18][CH:17]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Participants

7

Reactant 4

HCID 798IndoleHCID 24758Sodium hydrideHCID 57444250N-{3-[4-(chloromethyl)phenyl]pyrazin-2-yl}-2-(trifluoromethyl)benzenesulfonamide2×HCID 178418361HCID 178418361, compound

Product 1

HCID 11954423N-{3-[4-(1H-indol-1-ylmethyl)phenyl]pyrazin-2-yl}-2-(trifluoromethyl)benzenesulfonamideYield 62%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 1H-Indole (234 mg, 2.0 mmol, 1 eq) in dimethylformamide (10 mL) was added sodium hydride (80 mg, 2 mmol, 1 eq). After the evolution of hydrogen ceased, N-{3-[4-(chloromethyl)phenyl]pyrazin-2-yl}-2-(trifluoromethyl)benzene sulfonamide (intermediate 26) (854 mg, 2 mmol, 1 eq) in dimethylformamide (5 mL) was added and the reaction mixture heated to 80 degrees over 3 hours. The reaction was cooled, diluted with 30 mL of water and extracted with diethyl ether. The organic layer was dried over MgSO4, evaporated and purified by flash chromatography on silica gel eluting with AcOEt and cyclohexane to give pure N-{3-[4-(1H-indol-1-ylmethyl)phenyl]pyrazin-2-yl}-2-(trifluoromethyl)benzenesulfonamide as a yellow solid (630 mg, 1.24 mmol, yield: 62%, 97% HPLC purity).

Workup

  1. temperaturethe reaction mixture heated to 80 degrees over 3 hours
  2. temperatureThe reaction was cooled
  3. extractionextracted with diethyl ether
  4. dry with materialThe organic layer was dried over MgSO4
  5. customevaporated
  6. custompurified by flash chromatography on silica gel eluting with AcOEt and cyclohexane

Sources & evidence

ORD record
ord-d1ddd74af7914354a604573e908774c7
Source dataset
uspto-grants-2014_08
Patent number
US08796280B2

Reaction notes

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