تفاعل #162356

معادلة التفاعل

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

المذيبات

dichloromethane

dichloromethane

ظروف التفاعل

المعالجة

1. 1
   ترشيحthe mixture was filtered
2. 2
   غسيلwashing thoroughly with dichloromethane
3. 3
   تركيزThe filtrate was concentrated under reduced pressure
4. 4
   غسيلThe plate was eluted with dichloromethane
5. 5
   workup.ADDITIONFractions containing product material
6. 6
   أخرىwere further purified by HPLC
7. 7
   غسيلeluted with 60% methanol and 0.1% 2,2,2-trifluoroacetic acid in water

الإجراء التجريبي

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.

المصدر