1229236-83-2

1229236-80-9

7529-22-8

1229236-83-2

The general procedure for the synthesis of (4-chloro-2-fluorophenyl)(6-chloro-2-methyl-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-3-yl)methanone from the compound (CAS:1229236-80-9) and N-methylmorpholine oxides was carried out as follows: to the nitrogen-protected reaction vessel was added ethanol (12 L), (4-chloro-2-fluorophenyl)(6- chloro-2-methylimidazo[1,2-b]pyridazin-3-yl)methanone (897.70 g, 2.77 mol) and bis(2,4-pentanedione)oxovanadium(IV) (146.81 g, 553.67 mmol). A solution of 4-methylmorpholine 4-oxide (3.89 kg, 33.21 mol) in ethanol (6 L) was added dropwise over 150 min, controlling the reaction temperature between 23-33 °C. The reaction mixture was then heated to 40 °C for 48 hours. Upon completion of the reaction, the reaction mixture was cooled and a portion of the solvent (13 L) was removed by reduced pressure distillation to concentrate the reaction solution. The resulting mixture was filtered, the filter cake was washed with hexane (1 L) and finally dried to obtain the target product (728 g, 66.25% yield; melting point 145-147 °C; M+ = 423).