3-Bromo-6-chloroimidazo[1,2-b]pyridazine

3-Bromo-6-chloroimidazo[1, 2-b]pyridazine 478 mg (3.11 mmol) of 6-chloroimidazo[1, 2-b]pyridazine were introduced into 10 ml of chloroform under argon and, while cooling in ice, 664 mg (3.73 mmol) of N-bromo-succuinimide were added. After the addition was complete, the reaction mixture was stirred at room temperature overnight. The reaction mixture was then mixed with water and ethyl acetate and, after addition of saturated sodium bicarbonate solution, the phases were separated. The aqueous phase was extracted three more times with ethyl acetate. The combined organic phases were then washed with sat. sodium chloride solution and dried over sodium sulfate. In the final removal of the solvent in vacuo, the desired product was isolated in quantitative yield in the form of an amorphous white solid which was employed without further chromatographic purification in subsequent reactions.478 mg (3.11 mmol) of 6-chloroimidazo[1 , 2-b]pyridazine were introduced into 10 mL of chloroform under argon and, while cooling in ice, 664 mg (3.73 mmol) of N-bromosuccuinimide were added. After the addition was complete, the reaction mixture was stirred at rt over night. The reaction mixture was then mixed with water and ethyl acetate and, after addition of saturated sodium bicarbonate solution, the phases were separated. The aqueous phase was extracted three more times with ethyl acetate. The combined organic phases were then washed with sat. sodium chloride solution and dried over sodium sulfate. In the final removal of the solvent in vacuo, the desired product was isolated in quantitative yield in the form of an amorphous white solid which was employed without further chromatographic purification in subsequent reactions. 478 mg (3.1 1 mmol) of 6-chloroimidazo[1 , 2-b]pyridazine were introduced into 10 mL of chloroform under argon and, while cooling in ice, 664 mg (3.73 mmol) of N-bromosuccuinimide were added. After the addition was complete, the reaction mixture was stirred at room temperature overnight. The reaction mixture was then mixed with water and ethyl acetate and, after addition of saturated sodium bicarbonate solution, the phases were separated. The aqueous phase was extracted three more times with ethyl acetate. The combined organic phases were then washed with sat. sodium chloride solution and dried over sodium sulfate. In the final removal of the solvent in vacuo, the desired product was isolated in quantitative yield in the form of an amorphous white solid which was employed without further chromatographic purification in subsequent reactions. 478 mg (3.11 mmol) of 6-chloroimidazo[1 , 2-b]pyridazine were introduced into 10 mL of chloroform under argon and, while cooling in ice, 664 mg (3.73 mmol) of N-bromosuccuinimide were added. After the addition was complete, the reaction mixture was stirred at room temperature overnight. The reaction mixture was then mixed with water and ethyl acetate and, after addition of saturated sodium bicarbonate solution, the phases were separated. The aqueous phase was extracted three more times with ethyl acetate. The combined organic phases were then washed with sat. sodium chloride solution and dried over sodium sulfate. In the final removal of the solvent in vacuo, the desired product was isolated in quantitative yield in the form of an amorphous white solid which was employed without further chromatographic purification in subsequent reactions. 478 mg (3.1 1 mmol) of 6-chloroimidazo[1 , 2-b]pyridazine were introduced into 10 mL of chloroform under argon and, while cooling in ice, 664 mg (3.73 mmol) of N- bromosuccuinimide were added. After the addition was complete, the reaction mixture was stirred at room temperature overnight. The reaction mixture was then mixed with water and ethyl acetate and, after addition of saturated sodium bicarbonate solution, the phases were separated. The aqueous phase was extracted three more times with ethyl acetate. The combined organic phases were then washed with brine and dried over sodium sulfate. In the final removal of the solvent in vacuo, the desired product was isolated in quantitative yield in the form of an amorphous white solid which was employed without further chromatographic purification in subsequent reactions.478 mg (3.11 mmol) of 6-chloroimidazo[l, 2-b]pyridazine were introduced into 10 mL of chloroform under argon and, while cooling in ice, 664 mg (3.73 mmol) of /V-bromo- succinimide were added. After the addition was complete, the reaction mixture was stirred at room temperature overnight. The reaction mixture was then mixed with water and ethyl acetate and, after addition of saturated sodium bicarbonate solution, the phases were separated. The aqueous phase was extracted three more times with ethyl acetate. The combined organic phases were then washed with saturated sodium chloride solution and dried over sodium sulfate. In the final removal of the solvent in vacuo, the desired product was isolated in quantitative yield in the form of an amorphous white solid which was employed without further chromatographic purification in subsequent reactions.Step 2: 478 mg (3.1 1 mmol) of 6-chloroimidazo[1 , 2-b]pyridazine were introduced into 10 mL of chloroform under argon and, while cooling in ice, 664 mg (3.73 mmol) of N- bromo-succinimide were added. After the addition was complete, the reaction mixture was stirred at room temperature overnight. The reaction mixture was then mixed with water and ethyl acetate and, after addition of saturated sodium bicarbonate solution, the phases were separated. The aqueous phase was extracted three more times with ethyl acetate. The combined organic phases were then washed with saturated sodium chloride solution and dried over sodium sulfate. In the final removal of the solvent in vacuo, the desired product was isolated in quantitative yield in the form of an amorphous white solid which was employed without further chromatographic purification in subsequent reactions.Step 2: Preparation of 3-Bromo-6-chloroimidazo[1 , 2-b]pyridazine478 mg (3.1 1 mmol) of 6-chloroimidazo[1 , 2-b]pyridazine were introduced into 10 mL of chloroform under argon and, while cooling in ice, 664 mg (3.73 mmol) of N-bromosuccuinimide were added. After the addition was complete, the reaction mixture was stirred at rt over night. The reaction mixture was then mixed with water and ethyl acetate and, after addition of saturated sodium bicarbonate solution, the phases were separated. The aqueous phase was extracted three more times with ethyl acetate. The combined organic phases were then washed with sat. sodium chloride solution and dried over sodium sulfate. In the final removal of the solvent in vacuo, the desired product was isolated in quantitative yield in the form of an amorphous white solid which was employed without further chromatographic purification in subsequent reactions.A solution of 6-chloro-imidazo[1, 2-b]pyridazine (3.4g, 21.9 mmol) in CHCl6-Chloroimidazo[1, 2-b]pyridazine (8.5 g, 0.055 mol) and N-bromosuccinimide (10.0 g, 0.056 mol) were combined in chloroform (250 mL) and refluxed for 4 hours. The reaction was cooled with an ice bath and the solids filtered. The filtrate was diluted with chloroform (150 mL) and saturated NaIntermediate A 3-Bromo-6-chloroimidazo[1 , 2-b]pyridazine intermediate A To a solution of 6-chloroimidazo[1 , 2-b]pyridazine (5 g, 32.6 mmol) in acetonitrile (300 ml) was added 1-bromopyrrolidine-2, 5-dione (6.37 g, 35.8 mmol) and trifluoroacetic acid (0.75 mL). The resulting solution was allowed to stirr at room temperature overnight. The solvent was removed under reduced pressure and the residue was dissolved in EtOAc, washed with NaHCOs solution, water and brine, dried over Nab) 3-Bromo-6-chloroimidazo[1 , 2-b]pyridazine; Bromine (3.8 mL, 74.19 mmol) was added dropwise to a solution of 6-chloroimidazo [1 , 2-b]pyridazine (Preparation 1 a, 4.8 g, 31.06 mmol) in glacial acetic acid (80 mL) and the resulting mixture was stirred at ambient temperature for 20 minutes. The precipitate formed was collected by filtration, washed with diethyl ether several times and dried in vacuo. The solid obtained was partitioned between ethyl acetate and a saturated aqueous solution of potassium carbonate. The organic layer was separated and washed with a saturated aqueous solution of potassium carbonate, dried over magnesium sulphate and the solvent removed under reduced pressure. The crude was then treated with pentane, filtered and the solid obtained was dried in vacuo to yield the title compound (6.6 g, 92percent) as a pale yellow solid.LRMS (m/z): 232 (M+1)b) 3-Bromo-6-chloroimidazo[1, 2-b]pyridazine Bromine (3.8 mL, 74.19 mmol) was added dropwise to a solution of 6-chloroimidazo [1, 2-b]pyridazine (preparation 1 a, 4.8 g, 31.06 mmol) in glacial acetic acid (80 mL) and the resulting mixture was stirred at room temperature for 20 minutes. The precipitate formed was collected by filtration, washed with diethyl ether several times and dried in vacuo. The solid obtained was partitioned between ethyl acetate and a saturated aqueous solution of potassium carbonate. The organic layer was separated and washed with a saturated aqueous solution of potassium carbonate (x3), dried over magnesium sulphate and the solvent removed under reduced pressure. The crude was then treated with pentane, filtered and the solid obtained was dried in vacuo to yield the title compound (6.6 g, 92percent) as a pale yellow solid. LRMS (m/z): 232 (M+1)Bromine (1.74 mL, 34 mmol) was added dropwise to an ice cold mixture of acetic acid (2 mL) and 6-Chloro-imidazo[1, 2-b]pyridazine (6.72 g, 34 mmol) in methanol (300 mL). After the addition was completed the mixture was allowed to warm to room temperature and then stirred for one hour. The reaction was treated with saturated aqueous sodium bisulfite (100 mL) and the volatiles were removed under vacuum followed by the addition of ethyl acetate (150 mL). The solids were collected by filtration and dried under vacuum to give 3-bromo-6-chloro-1-yl-imidazo[1, 2-b]pyridazine as a pinkish solid (3.20 g): mp 157° C. The organic layer of the filtrate was dried over anhydrous magnesium sulfate, filtered and evaporated to give a second crop of 3-bromo-6-chloro-1-yl-imidazo[1, 2-b]pyridazine as a yellow solid. The combined solids were 6.71 g (86percent).3. 3-Bromo-6-chloro-imidazon , 2-blpyridazine (5)[0140] The 6-Chloro-imidazo[1 , 2-b]pyridazine (4) (500 mg, 0.0032 mol) was taken in glacial acetic acid (5 ml) and bromine (0.4 ml) was added slowly at room temperature. After 20 minutes, solid precipitated out and was filtered. The solid was washed with ether (3 x 15 ml) and dried under air to give 3-Bromo-6-chloro-imidazo[1 , 2-b]pyridazine (5) (400mg, yield = 60percent).-2 Synthesis of 3-bromo-6-chloroimadazo[1, 2-b]pyridazine

Molecular Weight:232.46
XLogP3:2.3
Hydrogen Bond Acceptor Count:2
Exact Mass:230.91989
Monoisotopic Mass:230.91989
Topological Polar Surface Area:30.2
Heavy Atom Count:11
Complexity:157
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes