DMF as a trifunctional organocatalyst: one-pot seven-component sequential synthesis of novel derivatives of tetrazoloquinolonecontaining aminofuropyrimidines

is a really attractive tool for performing effective reactions while avoiding the use of metals.[1] Normally,organocatalysts contaminate less and are less toxic than organometallic catalysts because they do not include metals within theirstructures, which is beneficial for industries that try to avoid using metals, such as the pharmaceutical industry. N,NDimethylformamide(DMF) is a versatile and multipurpose reagent which can has so many roles in chemical transformations.[2] Oftenused as a common solvent for chemical reactions and utilized widely in industry as a reagent, it has played an important role inorganic synthesis for a long time. It is also a common organocatalyst used in the synthesis of a wide range of organic compounds.The furopyrimidine ring system is found in a broad range of biologically active compounds.[3] Specifically, the furo[2,3-d]pyrimidines are an important class of annulated uracils with biological significance because of their connection with purine systems.It has numerous pharmacological and agrochemical applications viz. Akt1 kinase inhibitors, antifolates, and antivirus, as well aspotential radiation protection agents. Due to their biological importance, furo[2,3-d]pyrimidine derivatives have become synthetictargets for many organic and medicinal chemists. On the other hand, the tetrazole group has considered analogous to carboxylic groupas a pharmacophore. Several substituted tetrazoles show pronounced activities including antimicrobial, antimycobacterial,antiproliferative, anticancer and multi-drug resistance, etc.[4] The fusion of quinoline to the tetrazole ring is known to increase thebiological activity.[5] In particular, tetrazolo[1,5-a]quinoline-4-carbaldehyde serves as a key synthetic intermediate for the synthesisof novel medicinally valuable compounds.[5]Encouraged by their potential clinical applications and in continuation of our previous investigations on bio-potent complexheterocycles,[6] our efforts are focused to design and synthesize more biologically potent heterocyclic systems via combination ofdiverse therapeutically active moieties quinoline, tetrazole, furan and pyrimidindine together in a single scaffold. Herein, we reportthe synthesis of 2-chloroquionoline-3-carbaldehyde by a Vilsmeier–Haack formylation of acetanilide and phosphorus oxychloride inDMF and the sequential addition of sodium azide, acetic acid, barbituric acid and isocyanide to yield tetrazoloquinolone-containingaminofuropyrimidines in a one-pot seven-component Vilsmeier–Haack formylation/[3+2] cycloaddition/Knoevenagelcondensation/[4+1] cycloaddition/tautomerization sequential reaction. High rates of reactions at room temperature have led us toestablish a significant catalytic role for DMF in the Knoevenagel condensation stage. Eight new bonds and three new heterocycleswere assembled in a facile one-pot operation.

Keywords:

Organocatalysis , DMF , Tetrazoloquinoline-4-carbaldehyde , Multicomponent reactions , Furopyrimidines 1) POCl3