Potassium Carbonate → 2-[3,5-Bis(trifluoromethyl)phenyl]-N-[6-(2,2-dioxidohexahydropyrazino[2,1-c][1,4]thiazin-8(1H)-yl)-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide

HRID 2074910Notes

Reaction equation

HRID 2074910 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.[CH2:37]1[CH:42]2[CH2:43][NH:44][CH2:45][CH2:46][N:41]2[CH2:40][CH2:39][S:38]1(=[O:48])=[O:47].C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.O.C(OCC)(=O)C>[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[CH2:45][CH2:46][N:41]4[CH:42]([CH2:37][S:38](=[O:48])(=[O:47])[CH2:39][CH2:40]4)[CH2:43]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

7

Reactant 3

HCID 11430Potassium CarbonateHCID 235027842-(3,5-Bis(trifluoromethyl)phenyl)-N-(6-chloro-4-(4-fluoro-2-methylphenyl)pyrid-3-yl)-N,2-dimethylpropanamideHCID 59215787Octahydropyrazino[2,1-c][1,4]thiazine 2,2-dioxide

Product 1

HCID 592158102-[3,5-Bis(trifluoromethyl)phenyl]-N-[6-(2,2-dioxidohexahydropyrazino[2,1-c][1,4]thiazin-8(1H)-yl)-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamideYield 49.3%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

A 8 ml sealed vial was charged with 180 mg (0.31 mmol) of 2-[3,5-bis(trifluoromethyl)phenyl]N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577); 168 mg (0.62 mmol) of octahydropyrazino[2,1-c][1,4]thiazine 2,2-dioxide (D19), 128 mg (0.701 mmol) of potassium carbonate; the reagents were dissolved in 1 ml of DMSO and stirred at 150° C. for 18 h. The reaction mixture was diluted with water and ethyl acetate and the aqueous phase was extracted with ethyl acetate. The combined organic fractions were dried and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography (silica, cyclohexane/EtOAc 50/50 to EtOAc) affording the title compound as a white solid 105 mg.

Workup

  1. customA 8 ml sealed vial
  2. extractionthe aqueous phase was extracted with ethyl acetate
  3. customThe combined organic fractions were dried
  4. customthe solvent was removed under reduced pressure
  5. customThe crude product was purified by flash chromatography (silica, cyclohexane/EtOAc 50/50 to EtOAc)

Sources & evidence

ORD record
ord-4809f55a5f0f4e4ba786179251aabdee
Source dataset
uspto-grants-2011_04
Patent number
US07919491B2

Reaction notes

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