Cesium carbonate → (S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(1-(2-(trifluoromethyl)pyrimidin-5-yl)piperidin-4-yl)pyrrolidin-2-one

HRID 408015

반응식

HRID 408015 반응식
[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[NH:12][C@H:13]1[CH2:17][CH2:16][N:15]([CH:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)[C:14]1=[O:24].Br[C:26]1[CH:27]=[N:28][C:29]([C:32]([F:35])([F:34])[F:33])=[N:30][CH:31]=1.CC1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC(C)=CC=2)C2C=CC(C)=CC=2)C2C=CC(C)=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[NH:12][C@H:13]1[CH2:17][CH2:16][N:15]([CH:18]2[CH2:23][CH2:22][N:21]([C:26]3[CH:27]=[N:28][C:29]([C:32]([F:35])([F:34])[F:33])=[N:30][CH:31]=3)[CH2:20][CH2:19]2)[C:14]1=[O:24]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 4189906(S)-(-)-2,2'-Bis(di-p-tolylphosphino)-1, 1'-binaphthylHCID 336979635-Bromo-2-(trifluoromethyl)pyrimidineHCID 66800375(S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one

생성물 1

HCID 54670711(S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(1-(2-(trifluoromethyl)pyrimidin-5-yl)piperidin-4-yl)pyrrolidin-2-one수율 23.2%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매

반응 조건

온도
110 °C

실험 절차

A mixture of (S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one (Preparation E; 0.20 g, 0.56 mmol), 5-bromo-2-(trifluoromethyl)pyrimidine (0.15 g, 0.68 mmol), (S)-(−)-2,2′-bis(di-p-tolylphosphino)-1,1′-binaphthyl (0.076 g, 0.11 mmol), Pd(OAc)2 (0.025 g, 0.11 mmol), and Cs2CO3 (0.92 g, 2.8 mmol) were combined in degassed toluene (6 mL) and stirred in a sealed tube at 110° C. overnight. The solution was cooled, quenched with water, extracted with EtOAc, dried over MgSO4, and concentrated. Flash chromatography of the crude product on silica followed by trituration of the isolated material with 9:1 hexanes:DCM gave a white solid that was filtered and dried. The material was characterized as (S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(1-(2-(trifluoromethyl)pyrimidin-5-yl)piperidin-4-yl)pyrrolidin-2-one (0.064 g, 0.13 mmol, 23% yield). Mass spectrum (apci) m/z=502.1 (M+H). Optical purity was not determined.

후처리

  1. temperatureThe solution was cooled
  2. customquenched with water
  3. extractionextracted with EtOAc
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customDCM gave a white solid
  7. filtrationthat was filtered
  8. customdried

출처 및 근거

ORD 기록
ord-def9e9028d28466e9147e4c47c9f13e5
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08754226B2

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