反应详情

温度

35 °C

A mixture of 1,2-diethyl 4-(aminothioxomethyl)tetrahydro-1,2-pyridazinedicarboxylate (i.e. the product of Step F) (2.58 g, 0.0089 mol) and 2-bromo-1-(4,5-dihydro-5-(2,6-difluorophenyl)-3-isoxazolyl)ethanone (i.e the product of Step C) (2.63 g, 0.0086 mol) in methanol (20 mL) were carefully heated to 35° C. No exotherm was observed and the temperature was raised to between 45 to 50° C. and held at this temperature for 1 h. The reaction mixture was neutralised with aqueous sodium acetate (0.73 g in about 20 mL water). The reaction mixture was extracted with diethyl ether (3×), dried magnesium sulfate, filtered, and concentrated under reduced pressure to provide the title compound (4.18 g), which was used without purification.

1. temperaturethe temperature was raised to between 45 to 50° C.
2. extractionThe reaction mixture was extracted with diethyl ether (3×), dried magnesium sulfate
3. filtrationfiltered
4. concentrationconcentrated under reduced pressure