Hexafluoroisopropyl alcohol mediated synthesis of 2,3-dihydro-4H-pyrido[1,2-a]pyrimidin-4-ones

Abstract

An efficient synthesis of novel 2,3-dihydro-4H-pyrido[1,2-a]pyrimidin-4-ones has been reported. Inexpensive and readily available substrates, environmentally benign reaction condition, and product formation up to quantitative yield are the key features of this methodology. Products are formed by the aza-Michael addition followed by intramolecular acyl substitution in a domino process. The polar nature and strong hydrogen bond donor capability of 1,1,1,3,3,3-hexafluoropropan-2-ol is pivotal in this cascade protocol.

Synthesis of Hydrazone Derivatives of 4-[4-Formyl-3-(2-oxochromen-3-yl)pyrazol-1-yl]benzoic acid as Potent Growth Inhibitors of Antibiotic-resistant Staphylococcus aureus and Acinetobacter baumannii

“…In our quest to develop novel methodologies to synthesize bioactive molecules [23,24,25,26], we have reported the synthesis of novel pyrazole derivatives as potent antimicrobial agents [27,28,29]. Based on our lead molecules and known pharmacological properties of coumarin derivatives, we designed the novel molecules hoping to produce potent antimicrobial agents (Figure 1).…”

Modular synthesis of thiazoline and thiazole derivatives by using a cascade protocol

“…Thiazoline derivative has also been oxidized with DDQ (2,3-dichloro-5,6-dicyanobenzoquinone) to form thiazoles (entry C). 9 In a continuation of our efforts to get novel small molecule heterocycles 10 , 11 by using domino protocol, 12 we report the synthesis of thiazoline and thiazole derivatives using a domino protocol, mild reaction conditions, and readily available substrates ( Scheme 1 ).…”

“… 14 – 16 We have found HFIP as the best solvent and promoter for the synthesis of pyridopyrimidinones. 12 Keeping in mind the benign nature of HFIP, this solvent has been used as a promoter and the reaction medium for this domino reaction. In this methodology, work-up and column purification are not required.…”

“…Based on our experience with HFIP, 12 we tried the reaction of phenyl thiourea with ethyl 4-bromocrotonate ( E1 ) to synthesize thiazoline. The product formation was promising and we obtained a clean product in 90% yield (entry 1, Table 1 ).…”

“…For R = H, it undergoes keto–enol tautomerism to form thiazoline and for R = OEt, it undergoes elimination to form exo ylideneacetate derivative ( D ). [1,3]-Hydrogen shift 12 of ylideneacetate ( D ) leads to the formation of thiazole derivative ( Scheme 6 ).…”