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

HRID 2424622Notes

Reaction equation

HRID 2424622 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 recrystallization 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 recrystallization from ethyl acetate and hexanes

Sources & evidence

ORD record
ord-7887106809514d279be3f83b09ee404b
Source dataset
uspto-grants-2011_06
Patent number
US07964591B2

Reaction notes

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