Water → N-(2-cyclopropyl-2-hydroxyethyl)-6-(4-(2-(trifluoromethyl)benzoyl)piperazin-1-yl)pyridazine-3-carboxamide

HRID 2354763

반응식

HRID 2354763 반응식
[CH:1]1([CH:4]([OH:16])[CH2:5][NH:6][C:7]([C:9]2[N:10]=[N:11][C:12](Cl)=[CH:13][CH:14]=2)=[O:8])[CH2:3][CH2:2]1.N12CCCN=C1CCCCC2.[N:28]1([C:34]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=2[C:42]([F:45])([F:44])[F:43])=[O:35])[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1.O>CN(C=O)C.[N+](CCCC)(CCCC)(CCCC)CCCC.[I-]>[CH:1]1([CH:4]([OH:16])[CH2:5][NH:6][C:7]([C:9]2[N:10]=[N:11][C:12]([N:31]3[CH2:32][CH2:33][N:28]([C:34](=[O:35])[C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=4[C:42]([F:45])([F:43])[F:44])[CH2:29][CH2:30]3)=[CH:13][CH:14]=2)=[O:8])[CH2:3][CH2:2]1

참가 물질

7

반응물 4

HCID 962WaterHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 167337841-[2-(Trifluoromethyl)benzoyl]piperazineHCID 632963846-CHLOROPYRIDAZINE-3-CARBOXYLIC Acid (2-CYCLOPROPYL-2-HYDROXYETHYL)AMIDE

생성물 1

HCID 11751599N-(2-cyclopropyl-2-hydroxyethyl)-6-(4-(2-(trifluoromethyl)benzoyl)piperazin-1-yl)pyridazine-3-carboxamide수율 32%

시약·촉매·용매 2

HCID 67553Tetrabutylammonium Iodide촉매HCID 6228Dimethylformamide용매

반응 조건

온도
80 °C

실험 절차

To a solution of 6-chloropyridazine-3-carboxylic acid (2-cyclopropyl-2-hydroxyethyl)amide (58 mg, 0.24 mmol) in 10 mL of DMF was added 1,8-diazabicylco[5.4.0]undec-7-ene (0.109 g), piperazin-1-yl-(2-trifluoromethylphenyl)methanone (86.7 mg, 0.33 mmol) and Bu4NI (4 mg, 0.01 mmol). The mixture was heated at 80° C. overnight. Water was added and the mixture was extracted with ethyl acetate (2×15 mL). The organic extract was washed with diluted HCl, followed by bicarbonate solution and brine, then dried over Na2SO4 and concentrated. The residue was dissolved in small amount of dichloromethane and purified by column chromatography eluted with ethyl acetate to yield the product as a white solid (35.5 mg, 32% yield). 1H NMR (300 MHz, CDCl3) δ 8.24, 8.02, 7.73, 7.58, 7.34, 6.98, 4.04, 3.85, 3.52, 3.33, 3.10, 2.60-2.41, 0.95, 0.52, 0.32. MS (ES+) m/z 464.3 (M+1).

후처리

  1. extractionthe mixture was extracted with ethyl acetate (2×15 mL)
  2. extractionThe organic extract
  3. washwas washed with diluted HCl
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in small amount of dichloromethane
  7. custompurified by column chromatography
  8. washeluted with ethyl acetate

출처 및 근거

ORD 기록
ord-100eb7bcaa5b40c992fd7155b79fe0f5
출처 데이터셋
uspto-grants-2010_07
특허 번호
US07754711B2

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