Suzuki–Miyaura cross-coupling reactions of halo derivatives of 4H-pyrido[1,2-a]pyrimidin-4-ones

Abstract

The palladium-catalyzed Suzuki-Miyaura cross-coupling reactions of halo derivatives of 4H-pyrido[1,2-a]pyrimidin-4-one with (het)arylboronic acids allow easy access to (het)aryl and vinyl derivatives of this bicycle in good to excellent yields, even from chloro derivatives. The sequence of reactivity of the halogen in the different positions of the ring system was also investigated. 6-Phenyl-4H-pyrido[1,2-a]pyrimidin-4-one could be prepared by thermal cyclization of isopropylidene (6-phenylpyrid-2-ylamino)methylenemalonate, together with a small amount of 7-phenyl-1,4-dihydro-1,8-naphthyridin-4-one.

4H‐Pyrido[1,2‐a]pyrimidin‐4‐one, biologically important fused heterocyclic scaffold: Synthesis and functionalization

“…In 2011 , Hermecz group reported Pd‐catalyzed Suzuki‐Miyaura cross‐coupling method to easily access 2‐aryl‐4 H ‐pyrido[1,2‐ a ]pyrimidin‐4‐one 56 (Scheme 20) [37]. 2‐Halo‐pyrido[1,2‐ a ]pyrimidin‐4‐ones 54 were coupled with aryl boronic acids 55 in very excellent yields (81–97%).…”

Synthesis of 2-Arylpyridopyrimidinones, 6-Aryluracils, and Tri- and Tetrasubstituted Conjugated Alkenes via Pd-Catalyzed Enolic C–O Bond Activation–Arylation

“…2-Arylpyridopyrimidinones (Figure ) are prepared by a classical reaction of 2-aminopyridine with 3-aryl-3-oxopropanoate, but the method is nonflexible in incorporating versatile aryl moieties and poor to moderate yields in major cases . Another approach involves the preparation of 2-chloropyridopyrimidinone by deoxychlorination of pyridopyrimidin-2,4-dione using excess POCl 3 or SOCl 2 and subsequently the Suzuki coupling with arylboronic acid. However, such a deoxychlorination process is notorious and hazardous, generating enormous waste materials, while on the other hand, as part of the current momentum of a minimizing global environmental concern, the research into the development of green synthesis has been realized as an essential practice by chemists in both industry and academia. , Moreover, the reaction in POCl 3 /SOCl 2 solvent is detrimental for tolerating numerous functionalities and, thus, limits the potential in generating the substitution diversity in the product library.…”

Silver‐Catalyzed Direct Regioselective C3 Phosphonation of 4H‐pyrido[1,2‐a]pyrimidin‐4‐ones With H‐phosphites

“…[11,14] Hermecz's and Vanelle's groups reported the arylation of 4H-pyrido [1,2-a]pyrimidin-4-ones by Suzuki-Miyaura reaction. [15] Liang et al described the direct alkenylation of 2-methyl-4H-pyrido [1,2-a]pyrimidin-4-ones using oxygen as the oxidant. [16] Recently, the direct regioselectivity alkenylation and sulfenylation of 4H-pyrido[1,2-a]pyrimidin-4-ones catalyzed by palladium and iodine have successfully achieved in our laboratory (Scheme 1).…”

“…Other silver salts were tested and shown lower effective in this transformation (Table 1, entries 4-10). When carrying out the reaction with other nitrate instead of AgNO 3 , the highest yields just achieved to 42% by Cu(NO 3 ) 2 • 3H 2 O (Table 1, entries [11][12][13][14][15]. It is well-known that Mn(OAc) 3 • 2H 2 O is commonly used as radical initiators in phosphonation reaction.…”