One-pot synthesis of 1,2,3-triazole linked dihydropyrimidinones via Huisgen 1,3-dipolar/Biginelli cycloaddition

Abstract

The combination of the Biginelli reaction with click chemistry has been used for the one-pot synthesis of 1,2,3-triazole linked dihydropyrimidinones from azides, aromatic aldehydes containing a propargyl ether group, urea, and 1,3-dicarbonyl compounds using Cu(OAc)(2)/sodium ascorbate as catalyst in acetic acid under mild reaction conditions.

Ethyl 6-Methyl-2-oxo-4-{4-[(1-phenyl-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-1,2,3,4-tetrahydropyrimidine-5-carboxylate

“…The target compound LaSOM ® 293 was obtained as an amorphous yellow solid in an 84% yield. Very similar compounds to those reported here were obtained in a previous work with similar yields [10,11].…”

Multicomponent Syntheses based upon Copper‐Catalyzed Alkyne‐Azide Cycloaddition

“…A variety of substrates with both electronwithdrawing and electron-donating propensity were well tolerated. [166] Furthermore, Dabiri and co-workers [167] extended this concept to the synthesis of 1,2,3triazole-linked dihydropyrimidinones 95 in the sense of a CuAAC-Biginelli sequence (Scheme 71), furnishing considerably higher overall yields than the previously reported stepwise process under microwave irradiation. [165] Just recently, upon employing dimedone and 1,3-cyclohexanedione as active methylene compounds, the cyclocondensation-CuAAC sequence gave rise to the formation [(1,2,3-triazol-4-yl)methoxy-phenyl]-2H-indazolo [2,1b]phthalazinetriones 94 in a one-pot fashion (Scheme 70).…”

“…Just recently, upon employing dimedone and 1,3‐cyclohexanedione as active methylene compounds, the cyclocondensation‐CuAAC sequence gave rise to the formation [(1,2,3‐triazol‐4‐yl)methoxy‐phenyl]‐2 H ‐indazolo[2,1‐ b ]phthalazinetriones 94 in a one‐pot fashion (Scheme ) 166. Furthermore, Dabiri and co‐workers167 extended this concept to the synthesis of 1,2,3‐triazole‐linked dihydropyrimidinones 95 in the sense of a CuAAC‐Biginelli sequence (Scheme ), furnishing considerably higher overall yields than the previously reported stepwise process under microwave irradiation 168…”

An Overview of Recent Advances in the Applications of Click Chemistry in the Synthesis of Bioconjugates with Anticancer Activities

“…The copper‐catalyzed 1,3‐dipolar cycloaddition of an azide to a terminal alkyne is an easy route to tolerate a wide diversity of functional groups. The CuAAC reaction gives excellent yields and has been applied in organic synthesis, materials science, catalysis, and the biochemistry …”