Transition Metal-free Single Step Approach for Arylated Pyrazolopyrimidinones and Quinazolinones Using Benzylamines/Benzylalcohols/Benzaldehydes

Abstract

A transition metal-free, one step approach has been developed for the synthesis of pyrazolopyrimidinones using in-situ condensation of benzylamines, benzylalcohol and benzaldehyde with 4-amino-2-methyl-5-propyl-2H-pyrazole-3-carboxylic acid amide promoted by K 2 S 2 O 8 and water at room temperature. Present protocol tolerated various functional groups such as halides (Cl, F, Br), methoxy, ethoxy, hydroxyl, nitro, trifluromethyl, trifluoromethoxy and was also applicable to heterocyclic moieties. Different arylated pyrazolopyrimidinones were prepared in good to excellent yields. In the present reaction, K 2 S 2 O 8 is catalyzing the formation of imine as well helping in the cyclization to the desired product. We also reduced the industrially used synthesis steps for sildenafil analogues and prepared in three steps using present method. Arylquinazolinones were also synthesized in high yields using anthranilamide and benzylamines by this methodology.

Efficient Green Protocols for the Preparation of Pyrazolopyrimidines

“…[88] A one-step metal-free green synthetic protocol for the preparation of core structural motif of various arylated pyrazolopyrimidinones that is present in marketed drugs like Sildenafil was proposed by Hudwekar et al The desired molecule was prepared by in situ coupling of amide/primary amines and 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide in the presence of K 2 S 2 O 8 as catalyst and water as solvent at room temperature (Scheme 58). [89] Mechanism: The mechanistic pathway proposed that K 2 S 2 O 8 converts benzylamine into peroxide complex which is promoted by water via hydrogen bonding. Then, the release of H 2 O 2 leads to the formation of an imine intermediate, which is further converted into benzaldehyde by the release of ammonia.…”

Direct Construction of Diverse Polyheterocycles Bearing Pyrrolidinediones via Rh(III)‐Catalyzed Cascade C−H Activation/Spirocyclization

“…A cationic Rh(III) catalyst I can coordinate to an N-atom of 2-phenylquinazolinone (1 a), which subsequently activates sp 2 CÀ H bond at the ortho-position to generate the rhodacycle intermediate II. [23] Intramolecular aza-Michael addition of intermediate VI generates the final product 3 a. Then, Rh complex IV undergoes rapid E 2 elimination to generate intermediate V. [22] The protonation of intermediate V led to the intermediate VI and the Rh(III) active species.…”

“…[23] All other chemicals were purchased from Sigma-Aldrich, Alfa Aesar and TCI, and were used as received. Merck silica gel plates (Art.…”

“…Substrates 1 a-1 n were prepared according to the reported procedures. [23] All other chemicals were purchased from Sigma-Aldrich, Alfa Aesar and TCI, and were used as received. 1 H NMR spectra were recorded on a VNS (600 MHz) spectrometer in CDCl 3 /DMSO-d 6 using the solvent chemical shift of 7.24 ppm for CDCl 3 and 2.50 ppm for DMSO-d 6 as reference.…”

Aminoazole-Based Diversity-Oriented Synthesis of Heterocycles

“…Attempts to expand the range of the substrates have shown that aliphatic ketones couldn't be used as the reagents; N-substituted amides also did not undergo the condensation under such conditions. Application of the K 2 S 2 O 8 in acetonitrile–water mixture (1:1) at the room temperature (Hudwekar et al, 2017 ) allowed to apply the procedure not only for carbonyl compounds, but also for benzylamines or benzyl alcohol via their in situ oxidation. The formation of 1,5-dihydro-4 H -pyrazolo[3,4- d ]pyrimidin-4-ones 273 was also observed in the reaction of 5-amino-1 H -pyrazole-5-carboxamide 271 and methyl phenylacetate ( 272 ) in EtOH-EtONa (Tintori et al, 2015 ; Figure 21 ).…”