8-BROMO-6-CHLOROIMIDAZO[1,2-B]PYRIDAZINE

A solution of 4-bromo-6-chloropyridazin-3-amine (15.7 g, 75.3 mmol), 2-chloro-1, 1-diethoxyethane (13.9 g, 90.3 mmol) and PTSA (17.2 g, 90.3 mmol) in isopropanol (150 mL) was heated to 80° C. for 20 h. After cooling to room temperature, the solution was concentrated in vacuo. The resulting mixture was treated with a saturated NaHCOA solution of 4-bromo-6-chloropyridazin-3-amine (15.7 g, 75.3 mmol), 2-chloro- 1, 1- diethoxyethane (13.9 g, 90.3 mmol) and PTSA (17.2 g, 90.3 mmol) in isopropanol (150 mL) was heated to 80°C for 20 h. After cooling to room temperature, the solution was concentrated in vacuo. The resulting mixture was treated with a saturated NaHC03-amino-6-chloropyridazine (1.30 g, 10 mmol) was added to a 100 mL single-ended round bottom flask, (15 mmol), sodium bicarbonate (0.84 g, 10 mmol), and 5 g of chloroform and dichloromethane. The reaction mixture was stirred at 40 ° C for 15 hours with a magnetic stirrer.The reaction was terminated by adding 30percent aqueous solution of chloroacetaldehyde (3 mmol of chloroacetaldehyde), followed by further reaction at 45 ° C for 15 hours.TLC and GC determined that the reaction of 3-amino-4-bromo-6-chloropyridazine was complete. The reaction solution was filtered through suction and the cake was recrystallized from ethyl acetate and ethanol to give the pure product 6-chloro-8-bromoimidazo [1, 2-b] pyridazine. The filtrate was extracted with ethyl acetate and the extractant was removed by rotary evaporation The pure product 6-chloro-8-bromoimidazo [1, 2-b] pyridazine was obtained by recrystallization from water and ethanol mixed solvent. After drying, the yield was 89.25percent and the purity was 99.50percentIntermediate 1-12To a suspension of Intermediate 1-11 (1.6 g, 7.67 mmol) in water (50 mL) heated to 95 °C was added chloroacetaldehyde (50percent in water, 1.5 mL, 11.5 mmol). The reaction mixture was stirred at 95°C overnight. On cooling, NaHC0A solution of 4-bromo-6-chloropyridazin-3-amine (5.0 g, 24 mmol) and 2-chloroacetaldehyde (12 g, 75 mmol) in ethanol (100 mL) was heated at reflux for 15 h. 3-amino-4-bromo-6-chloropyridazine (0. 5g, 2. 4mmol) was added to a chloroacetaldhyde(12mmol) in ethyl acetate 20ml, heated under reflux for 24h, filtered and dried to give a brown solid, yield 70percentTo a solution of 4-bromo-6-chloropyridazin-3 -amine (6.0g, 28.8 mmol) was added 2-chloroacetaldehyde (22.60 g, 144 mmol) (50percent water solution). The reaction mixture was heated to 50 °C overnight. The reaction mixture was cooled to room temperature and concentrated. The residue was diluted with (3/4(3/4. Then, saturated aHC0