Potassium Carbonate → 2-[3,5-Bis(trifluoromethyl)phenyl]-N-[6-(1,1-dioxidohexahydro-5H-isothiazolo[2,3-a]pyrazin-5-yl)-4-(4-fluoro-2-methylphenyl)pyridin-3-yl]-N,2-dimethylpropanamide

HRID 421241Notes

Reaction equation

HRID 421241 reaction equation
[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C:13]([CH3:34])([CH3:33])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21](Cl)=[CH:22][C:23]=2[C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[CH3:31])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[S:37]1(=[O:47])(=[O:46])[N:41]2[CH2:42][CH2:43][NH:44][CH2:45][CH:40]2[CH2:39][CH2:38]1.C(=O)([O-])[O-].[K+].[K+].[NH4+].[Cl-]>CS(C)=O>[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C:13]([CH3:34])([CH3:33])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21]([N:44]3[CH2:43][CH2:42][N:41]4[S:37](=[O:47])(=[O:46])[CH2:38][CH2:39][CH:40]4[CH2:45]3)=[CH:22][C:23]=2[C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[CH3:31])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 235027842-(3,5-Bis(trifluoromethyl)phenyl)-N-(6-chloro-4-(4-fluoro-2-methylphenyl)pyrid-3-yl)-N,2-dimethylpropanamideHCID 59215775Hexahydro-2H-isothiazolo[2,3-a]pyrazine 1,1-dioxide

Product 1

HCID 160636092-[3,5-Bis(trifluoromethyl)phenyl]-N-[6-(1,1-dioxidohexahydro-5H-isothiazolo[2,3-a]pyrazin-5-yl)-4-(4-fluoro-2-methylphenyl)pyridin-3-yl]-N,2-dimethylpropanamideYield 34.8%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
180 °C

Procedure

A 8 ml sealed vial was charged with 100 mg (0.187 mmol) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), 98 mg (0.561 mmol) of hexahydro-2H-isothiazolo[2,3-a]pyrazine 1,1-dioxide (D10), 52 mg (0.374 mmol) of potassium carbonate; the reagents were dissolved in 0.8 ml of DMSO. The reaction mixture was heated at 180° C. for 36-48 hrs and then added to a saturated NH4Cl solution and back extracted with dichloromethane; the crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to cyclohexane/ethyl acetate 1:1 and affording 44 mg (0.065 mmol) of the title compound as pale yellow solid.

Workup

  1. customA 8 ml sealed vial
  2. extractionback extracted with dichloromethane
  3. customthe crude material was purified on SPE cartridge (Silica)
  4. washeluting with a gradient from cyclohexane/ethyl acetate 9:1, to cyclohexane/ethyl acetate 1:1

Sources & evidence

ORD record
ord-6c593240ed4f4859bf230b3a6e63bd82
Source dataset
uspto-grants-2012_01
Patent number
US08097618B2

Reaction notes

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