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 421263노트

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HRID 421263 반응식
[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

참가 물질

7

반응물 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

생성물 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-dimethylpropanamide수율 49.3%

시약·촉매·용매 3

HCID 679Dimethyl Sulfoxide용매HCID 962Water용매HCID 8857Ethyl Acetate용매

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온도
150 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-229384f60a644d7d8f302fd6957336ea
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08097618B2

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