Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

Abstract

SummaryA straightforward synthesis of 6-substituted 1-phenyl-3-trifluoromethyl-1H-pyrazolo[4,3-c]pyridines and the corresponding 5-oxides is presented. Hence, microwave-assisted treatment of 5-chloro-1-phenyl-3-trifluoromethylpyrazole-4-carbaldehyde with various terminal alkynes in the presence of tert-butylamine under Sonogashira-type cross-coupling conditions affords the former title compounds in a one-pot multicomponent procedure. Oximes derived from (intermediate) 5-alkynyl-1-phenyl-3-trifluoromethyl-1H-pyrazole-4-carbaldehydes were transformed into the corresponding 1H-pyrazolo[4,3-c]pyridine 5-oxides by silver triflate-catalyzed cyclization. Detailed NMR spectroscopic investigations (1H, 13C, 15N and 19F) were undertaken with all obtained products.

Synthesis and Antiproliferative Activity of 2,4,6,7-Tetrasubstituted-2H-pyrazolo[4,3-c]pyridines

“…Among biologically active pyrazolo [4,3-c]pyridines, 3-amino-2-phenyl-2H-pyrazolo [4,3-c]pyridine-4,6diol has shown inhibitory activity against p90 ribosomal S6 kinases 2 (RSK2) [45], while 3-aminopyrazolopyridinone derivatives were demonstrated to exhibit moderate inhibitory potency against CK1d, p38a, and aurora A kinases [46]. In a continuation of our work devoted to the preparation and study of the properties of various condensed and aryl coupled pyrazole derivatives [47][48][49][50][51][52][53][54][55], we recently reported a structure-activity relationship study on 2,4,6-trisubstituted-2H-pyrazolo [4,3-c]pyridines, several of which displayed good anticancer activity in vitro through arresting cell cycle in mitosis and the induction of apoptosis [54]. Inspired by these results, in the current work, we prepared a library of 2,4,6,7-tetrasubstituted-2H-pyrazolo [4,3-c]pyridines and examined the influence of an additional substituent at the 7-position on the biological and optical properties of the compounds.…”

Phthaloyl Dichloride–DMF Mediated Synthesis of Benzothiazole‐based 4‐Formylpyrazole Derivatives: Studies on Their Antimicrobial and Antioxidant Activities

“…The pyrazoles possessing a formyl group –CHO at the 4‐position are versatile organic synthetic intermediates for the synthesis of many heterocyclic ring systems such as pyrazolylpyrazolines , pyrazoloquinolinones , 4 H ‐pyrazolopyran , pyrazolylbenzoxazole , pyrazolothiadiazepines , pyrazolyloxazolone , pyrazolyloxadiazolines , pyrazolylthiadiazolines , imidazolylpyrazoles , pyrazolopyridines , chromenopyrazolones , and thiopyranothiazolylpyrazoles . These are equally important in the field of medicinal as well as pharmaceutical chemistry because of significant biological activities, such as anti‐inflammatory , antioxidant, antibacterial, and antifungal activities .…”