Synthesis of Novel Pyridopyrazoles by Reaction of Aminomethylene Malondialdehydes and 5-Amino-3-methylpyrazole Derivatives

We have shown previously that the reaction of 2,3,3-trimethyl-3H-indoles (indolenines) with the Vilsmeier reagent formed from N,N-dimethylformamide and phosphorus oxychloride (phosphoric trichloride), producing aminomethylene malondialdehydes, is a general process, by demonstrating the transformation using variously substituted 2,3,3-trimethyl-3H-indoles [1-4]. Additionally, we have described a simple and straightforward preparation of 4-(2,3,3- trimethyl-3H-indol-2-yl)-substituted pyrazoles by condensation of these aminomethylene malondialdehydes with hydrazine and aryl hydrazines [1,3,4]. Recently, we have been able to show that the principles embodied in transformations of simple indolenines via Vilsmeier formylations can be incorporated into more complex bisindolenine systems [5]. As a part of our continued interest to the amino heterocycles [6] we have now demonstrated the p-TSA catalyzed and green synthesis of novel pyridopyrazoles 2a-e by condensations of variously aminomethylene malondialdehydes 1 with electron-rich amino heterocycles in water (Scheme 1).