Chlorosuccinimide → (S)-1-(1-(3,5-dichloropyrazin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one

HRID 407989노트

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HRID 407989 반응식
[Cl:1]N1C(=O)CCC1=O.[Cl:9][C:10]1[N:11]=[CH:12][C:13]([N:16]2[CH2:21][CH2:20][CH:19]([N:22]3[CH2:26][CH2:25][C@H:24]([NH:27][C:28]4[CH:33]=[CH:32][C:31]([S:34]([CH3:37])(=[O:36])=[O:35])=[CH:30][C:29]=4[F:38])[C:23]3=[O:39])[CH2:18][CH2:17]2)=[N:14][CH:15]=1>CC(O)=O>[Cl:1][C:12]1[C:13]([N:16]2[CH2:21][CH2:20][CH:19]([N:22]3[CH2:26][CH2:25][C@H:24]([NH:27][C:28]4[CH:33]=[CH:32][C:31]([S:34]([CH3:37])(=[O:35])=[O:36])=[CH:30][C:29]=4[F:38])[C:23]3=[O:39])[CH2:18][CH2:17]2)=[N:14][CH:15]=[C:10]([Cl:9])[N:11]=1

참가 물질

4

반응물 2

HCID 31398ChlorosuccinimideHCID 54671276(S)-1-(1-(5-chloropyrazin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one

생성물 1

HCID 86688116(S)-1-(1-(3,5-dichloropyrazin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one수율 53.3%

시약·촉매·용매 1

HCID 176Acetic Acid용매

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온도
50 °C

실험 절차

N-Chlorosuccinimide (0.016 g, 0.12 mmol) was added to a mixture of (S)-1-(1-(5-chloropyrazin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one (Example 4; 0.042 g, 0.090 mmol) in AcOH (0.3 mL). The mixture was stirred at 50° C. for 1.5 hour and then cooled to ambient temperature. The volatiles were removed by a stream of flowing nitrogen and the resulting residue was stirred in a mixture of saturated aqueous Na2SO3 (1.5 mL) and EtOAc (1.5 mL) for 15 minutes. The mixture was then partitioned between saturated aqueous NaHCO3 (20 mL) and EtOAc (40 mL). The organic phase was washed successively with water (20 mL), water (20 mL) and brine (20 mL). The combined organic phases were dried over MgSO4, filtered and concentrated. The residue was purified on silica (eluting with 2:1 EtOAc/hexanes) to afford (S)-1-(1-(3,5-dichloropyrazin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one (0.024 g, 0.048 mmol, 53%) as a white solid. Mass spectrum (apci) m/z=502 (M+H).

후처리

  1. temperaturecooled to ambient temperature
  2. customThe volatiles were removed by a stream of flowing nitrogen
  3. stirringthe resulting residue was stirred in a mixture of saturated aqueous Na2SO3 (1.5 mL) and EtOAc (1.5 mL) for 15 minutes
  4. customThe mixture was then partitioned between saturated aqueous NaHCO3 (20 mL) and EtOAc (40 mL)
  5. washThe organic phase was washed successively with water (20 mL), water (20 mL) and brine (20 mL)
  6. dry with materialThe combined organic phases were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified on silica (eluting with 2:1 EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-cb7894c222ea4f00a62a12dbdd586059
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08754226B2

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