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

HRID 2401034Notes

Reaction equation

HRID 2401034 reaction equation
Cl[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:10]([NH:15][S:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[C:25]([F:28])([F:27])[F:26])(=[O:18])=[O:17])=[N:11][CH:12]=[CH:13][N:14]=2)=[CH:5][CH:4]=1.[NH:29]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:31]=[CH:30]1.CC(C)([O-])C.[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[N:29]1([CH2:2][C:3]2[CH:8]=[CH:7][C:6]([C:9]3[C:10]([NH:15][S:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[C:25]([F:28])([F:27])[F:26])(=[O:18])=[O:17])=[N:11][CH:12]=[CH:13][N:14]=3)=[CH:5][CH:4]=2)[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:31]=[CH:30]1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 798IndoleHCID 23665647Potassium tert-butoxideHCID 57444250N-{3-[4-(chloromethyl)phenyl]pyrazin-2-yl}-2-(trifluoromethyl)benzenesulfonamide2×

Product 1

HCID 11954423N-{3-[4-(1H-indol-1-ylmethyl)phenyl]pyrazin-2-yl}-2-(trifluoromethyl)benzenesulfonamideYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

N-{3-[4-(chloromethyl)phenyl]pyrazin-2-yl}-2-(trifluoromethyl)benzene sulfonamide (intermediate 26) (854 mg, 2 mmol, 1 eq) and 1H-Indole (234 mg, 2.0 mmol, 1 eq) were shaken in tetrahydrofuran (20 mL) and heated up to 50 degrees for 10 minutes. To the reaction mixture was added potassium tert-butoxide (4.5 mL of a 1M solution in THF). The reaction mixture was maintained to 50 degrees for 5 h, and then cooled down to room temperature. The reaction mixture was treated with 10 ml of an aqueous citric acid solution (20 g in 100 mL of water) and extracted with AcOEt. The organic layer was dried over MgSO4 and evaporated. The crude was purified similarly to Method A to give pure N-{3-[4-(1H-indol-1-ylmethyl)phenyl]pyrazin-2-yl}-2-(trifluoromethyl)benzenesulfonamide as a yellow solid (691 mg, 1.36 mmol, yield: 68%, 98% HPLC purity).

Workup

  1. temperatureheated up to 50 degrees for 10 minutes
  2. temperatureThe reaction mixture was maintained to 50 degrees for 5 h
  3. extractionextracted with AcOEt
  4. dry with materialThe organic layer was dried over MgSO4
  5. customevaporated
  6. customThe crude was purified similarly to Method A

Sources & evidence

ORD record
ord-4d6dbed3798241fc90ecb91a0e52c90f
Source dataset
uspto-grants-2014_08
Patent number
US08796280B2

Reaction notes

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