2-methyl-7-substituted pyrazolo[1,5-a]pyrimidines: highly regioselective synthesis and bromination

Abstract

Este trabalho descreve a reação de ciclocondensação de 3-amino-5-metil-1H-pirazol com 1,1,1-tricloro-4-alcóxi-3-alquen-2-onas [CCl 3 C(O)CH=C(R 1 )OR, onde R 1 /R = H/Me, Me/Et, Et/Me, Pr/Et, Bu/Me, iso-Bu/Me] e β-dimetilaminovinil cetonas [R 2 C(O)CH=CHNMe 2 , onde R 2 = Ph, Ph-4-Me, Ph-4-F, Ph-4-Cl, Ph-4-Br, Ph-4-NO 2 , fur-2-il, tien-2-il, pirrol-2-il, pyrid-2-il], em refluxo de ácido acético para a obtenção de uma série de catorze pirazolo [1,5-a]pirimidinas. Os produtos foram obtidos em bons rendimentos (65-98%). Este trabalho apresenta ainda uma metodologia simples e seletiva para a obtenção de 3-bromo-pirazolo [1,5-a] IntroductionAmong the broad range of templates, heterocycle scaffolds represent the most promising molecules as lead structures in the discovery of novel synthetic drugs 1 and the revision of synthetic methods for their obtainment are intense.2 In particular, the pyrazolo[1,5-a]pyrimidine heterocyclic can be found in a large number of pharmaceutical agents with a diverse range of activities. Pyrazolo [1,5-a] 13 However, a facile procedure that can incorporate diversity structural it is high desirable. There are a limitedness number and variety of pyrazolo pyrimidines trifluoromethyl substituted described in literature.14 Conversely, pyrazolo[1,5-a] pyrimidines trichloromethyl substituted are rare. 15 The most convenient method to construct trihalogenated compounds is to use halogen-containing building blocks as starting reagents. 16,17 Our research group developed a general procedure for preparing β-alkoxyvinyl trihalomethyl ketones by acylation of enol ethers and acetals using 2-Methyl-7-Substituted Pyrazolo[1,5-a]pyrimidines J. Braz. Chem. Soc. 206 functionalized acyl groups CX 3 CO (where X = F and Cl). 16In addition, we have exhaustively studied the versatility of the β-alkoxyvinyl trihalomethyl ketones on heterocyclic synthesis and our research have resulting in outstanding contributions to heterocyclic synthesis. 2,16 On the other hand, aminopyrazoles are known to be highly reactive heterocyclic compounds, e.g., the nucleophilic attack of C-4 of the aminopyrazoles on the carbonyl groups, 18 and the N-nucleophilic attack on aromatic aldehydes yielding aldimines, have been extensively reported.19 Aminopyrazoles also react as electron-rich dienophiles in the inverse electron demand Diels-Alder [4+2] cycloaddition reactions. 20The use of 3-and 5-aminopyrazoles as precursors of fused heterocycles, such as pyrazolo[1,5-a]pyrimidines 21 and pyrazolo [3,4-b]pyridines 22 has also been described. Additionally, halogenation of pyrazolo[1,5-a]pyrimidines can be used to obtain key substructures in a large variety of compounds with important biological activities, and the halogenated compounds also can be used as reagents in cross-coupling reactions with terminal acetylenes, organotin aryl derivatives or aryl boronic acids. 23 Thus, in the course of our investigations on heterocyclic chemistry and in view of the growing importance of halogenated heterocycles, the aim of this study is to show...

Structural studies of 2‐methyl‐7‐substituted pyrazolo[1,5‐a]pyrimidines

“…The synthesis of the following compounds was already described: 2‐methyl‐5‐phenyl‐7‐trifluoromethyl‐pyrazolo[1,5‐ a ]pyrimidine ( 1 ) [14], 2‐methyl‐5‐( p ‐tolyl)‐7‐trifluoromethylpyrazolo [1,5‐ a ]pyrimidine ( 2 ) [16], 2‐methyl‐7‐trichloromethylpyrazolo[1,5‐ a ]pyrimidine ( 4 ) [17], and 2,5‐dimethyl‐7‐trichloromethylpyrazolo[1,5‐ a ]pyrimidine ( 5 ) [17, 18].…”

“…Some of us already reported the X‐ray molecular structures of derivatives 2 and 5 [16, 18] and those of compounds 7 (a 3‐bromo derivative of 1 ) and 8 had also been published [14a, 17].…”

Deazapurine Analogues Bearing a 1H‐Pyrazolo[3,4‐b]pyridin‐3(2H)‐one Core: Synthesis and Biological Activity

“…Although the formation of two isomers ( 2a and 7a ) is, in principle, possible, the cyclocondensation proceeded with excellent regioselectivity in favour of 2a . Furthermore, no reaction with 4a or b acting as N‐C‐N (amidine type) nucleophile as described by Martins et al could be observed. In our substrates 4a and b the carbonyl group is probably responsible for the suppression of the formation of the tautomeric amidine structure, and thus exclusive reaction as enamine in the cyclisation reactions.…”

A facile environment-friendly one-pot two-step regioselective synthetic strategy for 3,7-diarylpyrazolo[1,5-a]pyrimidines related to zaleplon and 3,6-diarylpyrazolo[1,5-a]pyrimidine-7-amines assisted by KHSO $$_{4}$$ 4 in aqueous media

“…Further the structure was well supported by mass spectrometry. Plausible mechanisms for the formation of pyrazolo[1,5-a]pyrimidines (5 and 7) have been proposed in Schemes 4 and 5 [46].…”