HCID 17948959, 화합물 → HCID 15953078, 화합물

HRID 1924273노트

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HRID 1924273 반응식
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:14]O)=[C:9]([CH:11]3[CH2:13][CH2:12]3)[N:10]=2)[N:7]=1.[F:16][C:17]([F:25])=[CH:18][CH:19]1[CH2:23][NH:22][C:21](=[O:24])[CH2:20]1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:14][N:22]3[CH2:23][CH:19]([CH:18]=[C:17]([F:25])[F:16])[CH2:20][C:21]3=[O:24])=[C:9]([CH:11]3[CH2:12][CH2:13]3)[N:10]=2)[N:7]=1

참가 물질

4

반응물 2

HCID 17948959HCID 17948959, 화합물HCID 58009731(6-Chloro-2-cyclopropylimidazo[1,2-b]pyridazin-3-yl)methanol

생성물 1

HCID 15953078HCID 15953078, 화합물수율 28%

시약·촉매·용매 1

HCID 1140Toluene용매

실험 절차

A solution of (6-chloro-2-cyclopropylimidazo[1,2-b]pyridazin-3-yl)methanol x115 (889 mg, 3.97 mmol), 4-(2,2-difluorovinyl)pyrrolidin-2-one (643 mg, 4.37 mmol, 1.1 eq) and paratoluenesulfonic acid (76 mg, 0.40 mmol, 0.1 eq) in toluene (20 ml) is heated under reflux for 16 h. After cooling, the solvent is removed under reduced pressure, the crude product is dissolved in dichloromethane (100 ml). The organic layer is washed by water (150 ml). The aqueous layer is extracted by dichloromethane (100 ml). The cumulated organic layers are dried over MgSO4, filtered and evaporated under reduced pressure. The residue is purified by preparative chromatography over silicagel (benzine/AcOEt:60/40) to afford 1-[(6-chloro-2-cyclopropylimidazo[1,2-b]pyridazin-3-yl)methyl]-4-(2,2-difluorovinyl)pyrrolidin-2-one 62 after recrystallization in diisopropylether.

후처리

  1. temperatureunder reflux for 16 h
  2. temperatureAfter cooling
  3. customthe solvent is removed under reduced pressure
  4. dissolutionthe crude product is dissolved in dichloromethane (100 ml)
  5. washThe organic layer is washed by water (150 ml)
  6. extractionThe aqueous layer is extracted by dichloromethane (100 ml)
  7. dry with materialThe cumulated organic layers are dried over MgSO4
  8. filtrationfiltered
  9. customevaporated under reduced pressure
  10. customThe residue is purified by preparative chromatography over silicagel (benzine/AcOEt:60/40)

출처 및 근거

ORD 기록
ord-bd5f252e7c634ea086c29a1721c37ec5
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08178533B2

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