HCID 17948959、化合物 → HCID 15953078、化合物

HRID 1926784ノート

反応式

HRID 1926784 の反応式
[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

参加物

4

反応物 2

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

生成物 1

HCID 15953078HCID 15953078、化合物収率 28%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-749837b28f95444d84a79f48ba877876
出典データセット
uspto-grants-2012_05
特許番号
US08183241B2

反応ノート

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