New Synthesis of N‐(1H‐pyrazol‐5‐yl)‐hexahydroquinoline‐3‐carbonitrile and octahydropyrazolo[4′,3′:5,6]pyrimido[1,2‐a]quinoline‐6‐carbonitrile Derivatives from the Cyclic β‐Enaminones

Abstract

A facile and convenient synthesis of an interesting N‐(1H‐pyrazol‐5‐yl)‐hexahydroquinoline‐3‐carbonitrile and octahydropyrazolo[4′,3′:5,6]pyrimido[1,2‐a]quinoline‐6‐carbonitrile derivatives via the versatile readily accessible cyclic enaminones incorporating pyrazole moiety was accomplished.

Synthesis of novel hexahydroquinolines and 6‐amino‐2‐oxopyridine‐3,5‐dicarbonitriles incorporating sulfamethoxazole via [3 + 3] annulation

“…In continuation to our interest in the C─C bond formation reactions, the possibility of [3 + 3] atom combination reaction of the cyclic enamine incorporating sulfamethoxazole with α , β ‐unsaturated nitriles through Michael addition reaction was studied. First, the cyclic enamine 3 was prepared via the reaction of dimedone 1 with sulfamethoxazole 2 according to the procedure reported in the literature by us and by others (Scheme ). The Michael addition reaction of the cyclic enamine 3 with arylidenemalononitriles 4a‐e was then investigated.…”

“…The product is either 4‐aminohexahydroquinoline‐3‐carbonitrile 6 that results from initial addition of NH to the activated double bond in compound 4 to give 5 that readily cyclizes to 6 (pathway A) or 2‐aminohexahydroquinoline‐3‐carbonitrile 8 that results from the initial addition of enamine CH to the activated double bond in compound 4 to yield 7 that readily cyclizes to 8 (pathway B) (Scheme ). Although the 1 H and 13 C‐NMR cannot simply differentiate between the two isomers, we indubitably solved this problem and assumed that compound 8 to be the correct structure based on previous chemical elucidation and heteronuclear multiple bond correlation (HMBC) spectral analysis of some related compounds. In addition, we managed to confirm the structure through HMBC spectrum of compound 8c .…”

Bis(enaminones) as Versatile Precursors for Novel Bis([1,2,4]triazolo[1,5‐a]pyrimidines) and Bis(2‐thioxo‐2,3‐dihydropyrido[2,3‐d]pyrimidin‐4(1H)‐ones)

“…). In the last decades, our group has been heavily involved in a program aiming at exploring the synthetic potentiality of functionally substituted enamines . In continuation to this work, and in conjunction to our interest in the chemistry of bis(heterocycles) , we report herein on the reactivity patterns of enamines towards 1 H ‐1,2,4‐triazol‐5‐amine and 6‐amino‐2‐thioxopyrimidin‐4‐one.…”

“…). Enamines are used as intermediates for carbon–carbon bond formation reactions that include Michael addition , Hantzsch , and Biginelli reactions . Moreover, bis(heterocycles) have been reported to display wide range of bioactivities including antihypertensive , anticancer activities , and antiallergenic .…”

“…Enamines are one of the most dynamic areas in heterocyclic synthesis . They represent a class of vinyl–heteroatom derivatives that can be prepared via condensation of active methylene ketones with N , N ‐dimethylformamide dimethylacetal (DMF‐DMA) (Fig.…”