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

HRID 2356531

Reaktionsgleichung

Reaktionsgleichung von HRID 2356531
[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

Komponenten

7

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 67553Tetrabutylammonium IodideKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-cec12273eb4e4412a99da6ffa324337b
Quelldatensatz
uspto-grants-2010_07
Patentnummer
US07759348B2

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