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

Abstract

Treatment of 3-bromo-6-chloroimidazo[1,2-b]pyridazine with a variety of 1° or 2° alkylamines (2.0 equiv) with CsF (1.0 equiv), and BnNEt₃Cl (10 mol %) in DMSO at 100 °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° alkylamines, 1° amines with methylene- or ethylene-linked aromatic or heteroaromatic functionality (e.g. benzene, thiophene, furan, indole, and pyridine), and 2° 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.

Graphical Abstract

Keywords:

• Imidazo[1,2-b]pyridazine
• fluoride-promoted amination

Disclosure statement

The authors report there are no competing interests to declare.