Potassium Carbonate → 2-[3,5-Bis(trifluoromethyl)phenyl]-n{4-(4-fluoro-2-methylphenyl)-6-[8a-(hydroxymethyl)hexahydropyrrolo[1,2-a]pyrazin-2(1h)-yl]-3-pyridinyl}-n,2-dimethylpropanamide

HRID 2074925노트

반응식

HRID 2074925 반응식
[CH2:1]1[NH:6][CH2:5][CH2:4][N:3]2[CH2:7][CH2:8][CH2:9][C:2]12[CH2:10][OH:11].[F:12][C:13]([F:47])([F:46])[C:14]1[CH:15]=[C:16]([C:24]([CH3:45])([CH3:44])[C:25]([N:27]([C:29]2[CH:30]=[N:31][C:32](Cl)=[CH:33][C:34]=2[C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][C:36]=2[CH3:42])[CH3:28])=[O:26])[CH:17]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:19]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.O>[F:23][C:20]([F:21])([F:22])[C:18]1[CH:17]=[C:16]([C:24]([CH3:45])([CH3:44])[C:25]([N:27]([C:29]2[CH:30]=[N:31][C:32]([N:6]3[CH2:5][CH2:4][N:3]4[CH2:7][CH2:8][CH2:9][C:2]4([CH2:10][OH:11])[CH2:1]3)=[CH:33][C:34]=2[C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][C:36]=2[CH3:42])[CH3:28])=[O:26])[CH:15]=[C:14]([C:13]([F:47])([F:12])[F:46])[CH:19]=1

참가 물질

6

반응물 3

HCID 11430Potassium Carbonate2회HCID 235027842-(3,5-Bis(trifluoromethyl)phenyl)-N-(6-chloro-4-(4-fluoro-2-methylphenyl)pyrid-3-yl)-N,2-dimethylpropanamideHCID 45122045(Octahydropyrrolo[1,2-a]pyrazin-8a-yl)methanol

생성물 1

HCID 160640382-[3,5-Bis(trifluoromethyl)phenyl]-n{4-(4-fluoro-2-methylphenyl)-6-[8a-(hydroxymethyl)hexahydropyrrolo[1,2-a]pyrazin-2(1h)-yl]-3-pyridinyl}-n,2-dimethylpropanamide수율 10.5%

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 962Water용매

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온도
150 °C

실험 절차

To a solution of hexahydropyrrolo[1,2-a]pyrazin-8a(6H)-ylmethanol (D67, 35 mg) in methyl sulfoxide (1.5 mL), 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide [WO 2005/002577] (60 mg) and potassium carbonate (63 mg) were added. The resulting mixture was heated at 150° C. for 24 hours. The mixture was allowed to cool down to r.t and further D67 (17 mg) and potassium carbonate (15 mg) were added. The resulting mixture was heated at 150° C. for further 8 hours and then it was allowed to cool to r.t. and diluted with water (2 mL). The aqueous phase was extracted with ethyl acetate (3×2.5 mL). The combined organic extracts were dried and concentrated in vacuo to a residue which was purified twice by flash chromatography (first purification: EtOAc/Cycl from 80/20 to 100:0 then DCM/MeOH 95:5. Second purification: DCM/MeOH 98:2) to give the desired compound (7.7 mg) as yellow foam.

후처리

  1. temperatureto cool down
  2. temperatureThe resulting mixture was heated at 150° C. for further 8 hours
  3. temperatureto cool to r.t.
  4. extractionThe aqueous phase was extracted with ethyl acetate (3×2.5 mL)
  5. customThe combined organic extracts were dried
  6. concentrationconcentrated in vacuo to a residue which
  7. customwas purified twice by flash chromatography (
  8. customfirst purification
  9. customSecond purification

출처 및 근거

ORD 기록
ord-1ef9d2b7fb164b6bba20dd80dede7d92
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07919491B2

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