Reaktion #162356

Reaktionsgleichung

4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]hexahydropyridazine

product

4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]hexahydropyridazine

5-methyl-3-(trifluoromethyl)-1H-pyrazole-1-acetic acid

→

title compound

1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]tetrahydro-1(2H)-pyridazinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone

Lösungsmittel

dichloromethane

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Filtrationthe mixture was filtered
2. 2
   Waschenwashing thoroughly with dichloromethane
3. 3
   EinengenThe filtrate was concentrated under reduced pressure
4. 4
   WaschenThe plate was eluted with dichloromethane
5. 5
   workup.ADDITIONFractions containing product material
6. 6
   Sonstigewere further purified by HPLC
7. 7
   Wascheneluted with 60% methanol and 0.1% 2,2,2-trifluoroacetic acid in water

Vorschrift

A mixture of 4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]hexahydropyridazine (i.e. the product of Step H) (0.29 g, 0.83 mmol), 5-methyl-3-(trifluoromethyl)-1H-pyrazole-1-acetic acid (0.19 g, 0.91 mmol) and N,N-dicyclohexylcarbodiimide (0.19 g, 0.91 mmol) in dichloromethane (5 mL) was stirred at room temperature for 48 h. More dichloromethane was added to the reaction mixture, the mixture was filtered, washing thoroughly with dichloromethane. The filtrate was concentrated under reduced pressure and loaded onto a chromatotron plate (4 mm). The plate was eluted with dichloromethane, followed by a gradient of 0.5% to 2% methanol in dichloromethane. Fractions containing product material were further purified by HPLC using an Alltima C18 column (250×22 mm), monitored at wavelength 225 nm and eluted with 60% methanol and 0.1% 2,2,2-trifluoroacetic acid in water to provide the title compound (69 mg), a compound of the present invention.

Quelle