K₂S₂O₈-Promoted Consecutive Tandem Cyclization/Oxidative Halogenation: Access to 3-Halo-Pyrazolo[1,5-a]pyrimidines

Abstract

A one-pot methodology has been developed to synthesize 3-halo-pyrazolo­[1,5-a]­pyrimidine derivatives through the three-component reaction of amino pyrazoles, enaminones (or chalcone), and sodium halides. The use of easily accessible 1,3-biselectrophilic reagents like enaminones and chalcone offers a straightforward approach for the synthesis of 3-halo-pyrazolo­[1,5-a]­pyrimidines. The reaction proceeded through a cyclocondensation reaction between amino pyrazoles with enaminones/chalcone in the presence of K2S2O8 followed by oxidative halogenations by NaX-K2S2O8. Mild and environmentally benign reaction conditions, wide functional group tolerance, and scalability of the reaction are the attractive facet of this protocol. The combination of NaX-K2S2O8 is also beneficial for the direct oxidative halogenations of pyrazolo­[1,5-a]­pyrimidines in water.

Regioselective C(sp2)–H halogenation of pyrazolo[1,5-a]pyrimidines facilitated by hypervalent iodine(iii) under aqueous and ambient conditions

“…Specifically, a targeted approach involved subjecting 3-iodo-2-methyl-5,7-diphenylpyrazolo[1,5- a ]pyrimidine to well-established cross-coupling reactions, namely Suzuki–Miyaura coupling and Sonogashira coupling ( Scheme 4 ). 12 Under the conditions outlined in Scheme 4 , compound 3ag underwent reactions with phenyl boronic acid and phenyl acetylene, yielding products 5 and 7 with good yields of 85% and 73%, respectively. Following this, a series of controlled experiments were meticulously carried out to clarify the mechanistic foundations governing the halogenation reaction of pyrazolo[1,5- a ]pyrimidine.…”