One-pot, multi-component synthesis of novel 2-amino-[1,2,4]triazolo[1,5-a] pyrimidine-6-carboxamide derivatives as antiproliferative agents

A novel series of 2-amino-[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxamide derivatives has been achieved successfully via an efficient one-pot three-component Biginelli-like heterocyclization reaction between different benzaldehydes, 1H-1,2,4-triazole-3,5-diamine, and N-substituted acetoacetamides in the presence of p-toluenesulfonic acid as a catalyst. Moreover, the effects of different conditions on the reaction were well investigated. In addition, cancer cell growth inhibition activity for these target compounds was also explored, and analogue 5l demonstrated the most potent cytotoxic activity against different cancer cells. These finds indicat that 2-amino-[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxamide core could be well worth further optimization as a potential scaffold for development of anticancer agents.

A Direct and an Efficient Regioselective Synthesis of 1,2-Benzothiazine 1,1-dioxides, β-Carbolinones, Indolo[2,3-c]pyran-1-ones, Indolo[3,2-c]pyran-1-ones, Thieno[2,3-c]pyran-7-ones and Pyrano[3’,4’:4,5]imidazo[1,2-a]pyridin-1-ones via Tandem Stille/Heterocyclization Reaction

A general regioselective one-pot synthesis of 1,2-benzothiazine 1,1-dioxides from 2-iodo benzenesulfonamide moieties and allenylstannanes is described using a domino Stille-like/Azacyclization reaction. The conditions developed also opened a novel access to β-carbolinones, indolopyranones, thienopyranones and pyrano-imidazopyridines.

SYNTHESIS OF 4-HETARYL-2-(DICHLOROMETHYL)PYRAZOLO[1,5-a][1,3,5]-TRIAZINES

New pyrazolo[1,5-a][1,3,5]triazines with a heteroaromatic substituent in position 4 and dichloromethyl moiety in position 2 were obtained via a heterocyclization reaction of readily available reagents - N-(2,2-dichloro-1-cyanoethenyl)carboxamides and 3(5)-aminopyrazoles. The high efficiency of the proposed method for the synthesis of 2-(dichloromethyl)-pyrazolo[1,5-a][1,3,5]triazines with furan-2-yl, thien-2-yl, and pyridine-3-yl substituents was demonstrated.

N-Methylated 1,8-Diaminonaphthalenes as Bifunctional Nucleo­philes in Reactions with α,ω-Dihalogenoalkanes: A Facile Route to Heterocyclic and Double Proton Sponges

The reaction of 1-dimethylamino-8-(methylamino)naphthalene with 1,3-dibromopropane chemoselectively leads to the product of N,N′-heterocyclization, while in the case of 1,4-dibromobutane and 1,2-bis(bromomethyl)benzene the process results in heterocyclization onto the same nitrogen atom with the formation of previously unknown 1-dimethylamino-8-pyrrolidino- and 1-dimethylamino-8-isoindolino-naphthalenes. The same reactions conducted without adding any auxiliary base lead to the formation of N,N′-linked double proton sponges as a new type of polynitrogen organic receptor. Proceeding as a sequence of quaternization–demethylation–cyclization steps, this heterocyclization process can also be used to construct six-membered rings (piperidino, morpholino), albeit in lower yields. The ability of 1,2-dibromoethane to brominate N-alkylated 1,8-diaminonaphthalenes is also described. It is shown for the first time that a commercially available 1,8-bis(dimethylamino)naphthalene (DMAN) can be used as a starting material in a heterocyclization reaction, which via a one-pot approach and in a short time can be converted into 1,5-dimethylnaphtho[1,8-bc]-1,5-diazacyclooctane or 1-dimethylamino-8-(pyrrolidin-1-yl)naphthalene.

Catalyst-Free Synthesis of Polysubstituted 5-Acylamino-1,3-Thiazoles via Hantzsch Cyclization of α-Chloroglycinates

A catalyst-free heterocyclization reaction of α-chloroglycinates with thiobenzamides or thioureas leading to 2,4-disubstituted-5-acylamino-1,3-thiazoles has been developed. The methodology provides straightforward access to valuable building blocks for pharmaceutically relevant compounds.