Microwave‐Assisted Suzuki–Miyaura and Sonogashira Coupling of 4‐Chloro‐2‐(trifluoromethyl)pyrido[1,2‐e]purine Derivatives

Abstract

The convenient preparation of three imidazo[1,2‐a]pyridine‐2‐carboxamide intermediates is reported through known Strecker–Ugi type multicomponent reactions, Tschitschibabin type condensations, and further synthetic sequences. The derivatives were then efficiently converted to novel 4‐chloro‐2‐(trifluoromethyl)pyrido[1,2‐e]purines by their original reactions with 2,2,2‐trifluoroacetamide, followed by subsequent dehydroxychlorination reactions. These compounds were cross‐coupled under microwave irradiation through SuzukiMiyaura and Sonogashira palladium(0) catalysis to various aromatic and alkynyl reagents, thus providing the related C‐4 substituted pyrido[1,2‐e]purines of biological interest in good yields.

Pyrido[1,2-e]purine: Design and Synthesis of Appropriate Inhibitory Candidates against the Main Protease of COVID-19

“…With regard to the significant properties of pyrido­[1,2- e ]­purine, developing novel strategies for synthesizing different skeletons of these systems has attracted significant attention. It has been demonstrated in some classical methods that the functionalized imidazo­[1,2- a ]­pyridine system can be employed as a practical substance in combination with various reagents to afford pyrido­[1,2- e ]­purine scaffolds. , The other synthetic routes using purine as the precursor include ring-closing metathesis followed by oxidation of 8,9-diallylpurines, copper-catalyzed one-pot sequential allylic amination/cycloisomerization of the Boc-protected purine, sequential Suzuki coupling of 9-(2-bromophenyl)­purines with 2-bromophenylboronic acid followed by intramolecular C–H arylation, and intramolecular cyclization reactions of 1,3-bis­(4-methoxybenzyl)-5-(pyridin-2-ylamino)­pyrimidine-2,4­(1 H ,3 H )-diones . These methods have shown multistep reactions in the construction of pyrido­[1,2- e ]­purine structures.…”

Recent Developments towards the Synthesis of Pyrimidopyrimidine and Purine Derivatives

“…[133] The reaction of the building block c,d). [134] The 3-aminoimidazo ). [135] The reaction proceeded smoothly with 20 mol% FeCl 2 .4H 2 O as a catalyst in the presence of green oxidant O 2 at 120 °C in DMSO.…”

“…Recently, a similar reaction sequence has been applied by Tber et al . for the preparation of 4‐chloro‐2‐(trifuoromethyl)pyrido[1,2‐ e ]purine derivatives ( 190 ) starting from 2‐aminopyridine ( 168 c,d ) [134] . The 3‐aminoimidazo[1,2‐ e ]pyridine‐2‐carboxymide ( 173 a ) has been prepared by following Guchhait et al procedure from the reaction of 2‐aminopyridine ( 168 a ) with ethylglyoxalate in the presence of TMSCN and DABCO under microwave irradiation and then, treatment with aqueous ammonia at 70 °C (Scheme 55).…”

Microwave-Assisted Synthesis: Can Transition Metal Complexes Take Advantage of This “Green” Method?

“…MW irradiation has been widely used in the case of metal-catalyzed synthetic procedures [13,[37][38][39][40][41][42][43][44][45][46][47][48]. This includes also facile, green, and useful click reactions, which are characterized by the formation of a single product in high yield, the elimination of byproducts, atom economy, the use of mild reaction conditions, water compatibility, and the use of simple purification processes [49][50][51][52].…”