An Efficient Synthesis of New 7-Trifluoromethyl-2,5-disubstituted Pyrazolo[1,5-a]pyrimidines

Abstract

A novel two-step synthesis of trifluoromethylated 3,5-disubstituted pyrazolo[1,5-a]pyrimidines is reported from 3-aminopyrazoles and ethyl 4,4,4-trifluorobut-2-ynoate. The synthetic route begins with the one-pot synthesis of 7-trifluoromethylated pyrazolo[1,5-a]pyrimidin-5-ones by condensation of 3-aminopyrazoles with a fluorinated alkyne. The products obtained are used as building blocks to synthesize directly, with excellent yields via C–O bond activation, a library of new fluorinated 3,5-disubstituted pyrazolo[1,5-a]pyrimidines of biological interest. This operation efficiently allows C–C, C–N and C–S bond formation.

Synthesis of Trifluoromethylated Pyrimido[1,2-b]indazole Derivatives through the Cyclocondensation of 3-Aminoindazoles with Ketoester and Their Functionalization via Suzuki-Miyaura Cross-Coupling and SNAr Reactions

“…As part of our on-going effort in the synthesis of novel fluorinated heterocycles [ 27 , 28 , 29 , 30 , 31 ], we report herein a convenient and efficient synthetic strategy that enables the construction of trifluoromethylated pyrimido[1,2- b ]indazole derivatives.…”

“…Therefore, the development of an efficient and facile method to approach fluorinated tricyclic compounds is highly desirable. As part of our on-going effort in the synthesis of novel fluorinated heterocycles [27][28][29][30][31], we report herein a convenient and efficient synthetic strategy that enables the construction of trifluoromethylated pyrimido[1,2-b]indazole derivatives. As part of our on-going effort in the synthesis of novel fluorinated heterocycles [27][28][29][30][31], we report herein a convenient and efficient synthetic strategy that enables the construction of trifluoromethylated pyrimido[1,2-b]indazole derivatives.…”

Simple and Expedient Access to Novel Fluorinated Thiazolo- and Oxazolo[3,2-a]pyrimidin-7-one Derivatives and Their Functionalization via Palladium-Catalyzed Reactions

“…Continuing our interest in the development of efficient methods for the synthesis of new fluorinated heterocyclic compounds with possible biological properties [41][42][43][44][45][46][47], we Classically, Thiazolo and oxazolo[3,2-a]pyrimidin-7-one derivatives have been synthesized by reactions of the corresponding 2-aminoazoles with a symmetric alkyne such as dialkyl acetylenedicarboxylates [28][29][30][31][32][33][34][35][36] (Figure 2a), or an asymmetric alkyne such as ethyl propiolate derivatives [37][38][39][40] (Figure 2b). However, despite their relevance, these procedures have several drawbacks such as a lack of generality, poor regioselectivity, the use of expensive reagents or less available reagents, as well as unsatisfactory yields.…”

“…Continuing our interest in the development of efficient methods for the synthesis of new fluorinated heterocyclic compounds with possible biological properties [41][42][43][44][45][46][47], we Despite the numerous approaches described in the literature for the synthesis of nonfluorinated thiazolo-or oxazolo[3,2-a]pyrimidin-7-one derivatives, the incorporation of fluorinated groups into these scaffolds has never been reported to date. Thus, the development of a simple and efficient method using readily available starting materials to access new fluorinated thiazolo-and oxazolo[3,2-a]pyrimidin-7-one derivatives is highly desired.…”

An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity

“…So far, different synthetic routes towards pyrazolo [1,5-a]pyrimidines have been reported. These methods have been mainly included the condensation of 3-aminopyrazoles with 1,3-bis electrophilic substrates [51][52][53][54][55][56][57][58][59] , 1,2-allenic lactones 60 , β-halovinyl aldehyde 61 , and activated alkynes 62,63 .…”