Potassium Carbonate → 6-[4-(2-TRIFLUOROMETHYLTHIOBENZOYL)PIPERAZIN-1-YL]-PYRIDAZINE-3-CARBOXYLIC Acid (2-CYCLOPROPYLETHYL)AMIDE

HRID 2056613Notes

Reaction equation

HRID 2056613 reaction equation
[N:1]1([C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15]([F:18])([F:17])[F:16])=[S:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH:19]1([CH2:22][CH2:23][NH:24][C:25]([C:27]2[N:28]=[N:29][C:30](Cl)=[CH:31][CH:32]=2)=[O:26])[CH2:21][CH2:20]1.C([O-])([O-])=O.[K+].[K+]>[N+](CCCC)(CCCC)(CCCC)CCCC.[I-].O1CCOCC1>[CH:19]1([CH2:22][CH2:23][NH:24][C:25]([C:27]2[N:28]=[N:29][C:30]([N:4]3[CH2:5][CH2:6][N:1]([C:7](=[S:8])[C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=4[C:15]([F:18])([F:16])[F:17])[CH2:2][CH2:3]3)=[CH:31][CH:32]=2)=[O:26])[CH2:21][CH2:20]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 655615656-Chloro-N-(2-cyclopropylethyl)pyridazine-3-carboxamideHCID 86025958Methanethione, 1-piperazinyl[2-(trifluoromethyl)phenyl]-

Product 1

HCID 114086306-[4-(2-TRIFLUOROMETHYLTHIOBENZOYL)PIPERAZIN-1-YL]-PYRIDAZINE-3-CARBOXYLIC Acid (2-CYCLOPROPYLETHYL)AMIDEYield 76%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of piperazin-1-yl-(2-trifluoromethylphenyl)methanethione (1.1 g, 4.0 mmol), 6-chloropyridazine-3-carboxylic acid (2-cyclopropylethyl)amide (0.98 g, 3.98 mmol), K2CO3 (0.83 g, 6.0 mmol) and n-Bu4NI (0.010 g) in dioxane (10 mL) was heated to reflux for 21 h, and then concentrated. The residue was purified by column chromatography and recrystalization from ethyl acetate and hexanes to afford the title compound in 76% yield (1.42 g). m.p. 117-120° C. 1H NMR (300 MHz, CDCl3) δ 8.05-7.93, 7.65, 7.55, 7.44, 7.24, 6.98, 4.61-4.40, 3.98-3.40, 1.51-1.47, 0.73-0.64, 0.44-0.35, 0.07-0.01. 13C NMR (75 MHz, CDCl3) δ 197.0, 162.8, 159.6, 145.6, 140.2, 132.4, 128.8, 127.2, 127.0, 126.9, 125.5, 124.8, 124.4, 124.0, 121.8, 112.5, 50.4, 47.6, 44.2, 43.6, 40.0, 39.6, 34.4, 8.6, 4.2. MS (ES+) m/z 464.0 (M+1).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 21 h
  3. concentrationconcentrated
  4. customThe residue was purified by column chromatography and recrystalization from ethyl acetate and hexanes

Sources & evidence

ORD record
ord-b0526fbc1a65445c9250f9e4057d8f5f
Source dataset
uspto-grants-2008_02
Patent number
US07335658B2

Reaction notes

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