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

HRID 2356531

Reaction equation

[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

Participants

Conditions

Temperature: 80 °C

Procedure

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).

Workup

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

Sources & evidence

ORD record: ord-cec12273eb4e4412a99da6ffa324337b
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07759348B2

Linked notes

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