Imidazo[1,2-b]pyridazine-2-carboxylic acid, 6-chloro-, ethyl ester

Brown Solid

To slurry of 6-chloropyridazin-3 -amine (10.00 g, 77 mmol) in ethanol (30 mL) at 0 °C was added ethyl 3-bromo-2-oxopropanoate (20.07 g, 93 mmol) in ethanol (5 mL) via pipette. After complete addition, the cooling bath was removed and the reaction mixture was allowed to stir at room temperature for 15 min., then heated at 80 °C for 30 min. to give a clear solution. After heating for 2 h, the mixture was cooled to room temperature and the resulting precipitated solid was collected and rinsed with cold ethanol to afford beige solid. The solid was suspended in aqueous saturated NaHCC and was stirred for 30 min. before collecting the solid by vacuum filtration. The filter cake was rinsed with water, dried on filter, and further dried under vacuum to afford a tan solid as ethyl 6- chloroimidazo[l , 2-b]pyridazine-2-carboxylate (8.8 g, 39.0 mmol, 51percent yield). NMR (400MHz, chloroform-dTo a solution of 3-amino-6-chloropyridazine (1, 31 g, 240 mmol) in EtOH (1 L) was added ethylbromopyruvate (39.2 mL, 312 mmol) dropwise. The reaction mixture was refluxed for 18 hours.Upon completion, the reaction mixture was evaporated to dryness. The residue was dissolved inEtOAc (800 mL) and H2O (800 mL) was added. The organic layer was washed with H2O (4 ×800 mL), and the combined organic extracts were dried over MgSO4, filtered and evaporated todryness. H2O (400 mL) was added and stirred at RT for at least 15 min and the solid formed was filtered, washed with H2O to give ethyl 6-chloroimidazo[1, 2-b]pyridazine-2-carboxylate (2) as a beige solid (25 g, 46percent).3-amino-6-chloropyridazine (20 g; 154.4 mmol) and ethyl bromopyruvate (38.9 mL; 308.8 mmol) in EtOH (90 mL) were refluxed overnight. The reaction mixture was cooled to room temperature, water and DCM were added. The organic layer was separated, dried over MgS03-amino-6-chloropyridazine (20 g; 154.4 mmol) and ethyl bromopyruvate (38.9 mL; 308.8 mmol) in EtOH (90 mL) were refluxed overnight. The reaction mixture was cooled to room temperature, water and DCM were added. The organic layer was separated, dried over MgSOzi, filtered and evaporated. The residue was purified by chromatography over silica gel (Irregular SiOH, 15-40 μιη, 300 g, gradient from 97percent heptane 30percent EtOAc to 50percent Heptane 50percent EtOAc). The fractions containing the product were collected and evaporated to dryness to afford 13.5 g (39percent) of intermediate 66.3-amino-6-chloro pyridazine (10 g, 77.2 mmol) was dissolved in absoluteethanol (120 mL), and then slowly added ethyl bromopyruvate (11.70 mL, 92.6mmol) was added thereto, the addition was complete the reaction It was heatedat reflux overnight. After completion of the reaction by TLC, the reactionsolution was cooled to room temperature, most of the solvent was removed underreduced pressure, the residue was dissolved in saturated sodium bicarbonatesolution, and extracted with dichloromethane (50 mLx3), the organic phase waswashed with water, saturated brine, dried over anhydrous dried over sodiumsulfate, filtered, and concentrated under reduced pressure, the residue waspurified by silica gel column chromatography to give Intermediate 6-Chloro -imidazo [l, 2-b] pyridazine-2-carboxylate (pale yellow solid, 8.2 g).

Anti-inflammatory agent

Molecular Weight:225.63
XLogP3:1.8
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:225.0305042
Monoisotopic Mass:225.0305042
Topological Polar Surface Area:56.5
Heavy Atom Count:15
Complexity:252
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes