An efficient synthesis of C-6 aminated 3-bromoimidazo[1,2-b]pyridazines

Treatment of 3-bromo-6-chloroimidazo[1,2-b]pyridazine with a variety of 1 degrees or 2 degrees alkylamines (2.0 equiv) with CsF (1.0 equiv), and BnNEt3Cl (10 mol %) in DMSO at 100 degrees C (24 hours) gave the corresponding C-6 aminated products in excellent isolated yields (79-98%; ave. yield = 92%). These conditions worked well for simple unfunctionalized 1 degrees alkylamines, 1 degrees amines with methylene- or ethylene-linked aromatic or heteroaromatic functionality (e.g. benzene, thiophene, furan, indole, and pyridine), and 2 degrees alkylamines such as pyrrolidine, morpholine, and piperidine were also well tolerated. The method is cost-effect, providing C-6 aminated products in consistently high yields, while at the same time utilizing far less toxic fluoride (10 fold less), than previous fluoride-promoted aminations.

Automated summary

A new method for synthesizing C-6 substituted products has been discovered in this study, which utilizes lower doses of fluoride and CsF as a catalyst, with high reaction yields and cost-effectiveness under suitable conditions.