Preparation of 2‐phenyl‐2‐hydroxymethyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline and 2‐methyl‐4‐oxo‐3,4‐dihydroquinazoline derivatives formation

Abstract

The cyclization of phenacyl anthranilate has been studied with the aim to develop the synthesis of 2‐(2′‐aminophenyl)‐4‐phenyloxazole. However, a different course of the reaction than expected was observed. 2‐Phenyl‐2‐hydroxymethyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline (3a) was formed by the reaction of phenacyl anthranilate (2) with ammonium acetate under various conditions. 3‐Hydroxy‐2‐phenyl‐4(1H)‐quinolinone (4) arose by heating compound 3a in acetic acid. The same compound was obtained by melting compound 3a, but the yield was lower. Different types of products resulted in the reaction of compound 3a with acetic anhydride. Under mild conditions acetylated products 2‐acetoxymethyl‐2‐phenyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline (7a) and 2‐acetoxymethyl‐3‐acetyl‐2‐phenyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline (8) were prepared. If the reaction was carried out under reflux of the reaction mixture, molecular rearrangement took place to give cis and trans 2‐methyl‐4‐oxo‐3‐(1‐phenyl‐2‐acetoxy)vinyl‐3,4‐dihydroquinazolines (9a and 9b). All prepared compounds have been characterised by their 1H, 13C and 15N NMR spectra, IR spectra and MS.

Identification of Eukaryotic Translation Elongation Factor 1-α 1 Gamendazole-Binding Site for Binding of 3-Hydroxy-4(1H)-quinolinones as Novel Ligands with Anticancer Activity

“…Phenacyl ester 12 was prepared by the reaction of anthranilic acid with bromoketone 11 . The cyclization to 3-HQ 13 was inspired by a well-established method described previously. , Hydrolysis of the methyl ester afforded carboxylate 3-HQ 14 and, following its amidation, carboxamide 3-HQ 15 . These derivatives were subsequently transformed to the desired 3-HQs 4 and 5 and 6 and 7 by nucleophilic substitution with secondary amines (piperidine or morpholine) in a microwave reactor.…”

2,3-Dihydroquinazolin-4(1H)-one as a privileged scaffold in drug design

“… 237 The intramolecular cyclization of 2-phenyl-ethyl anthranilate in the presence of NH 4 OAc led to the respective DHQs. 238 The oxidation of benzylamines to the corresponding N -benzylbenzaldimines was also investigated and used for the synthesis of DHQ derivatives. 239 …”

Solid-Phase Synthesis of 3-Hydroxy-6-Nitroquinolin-4(1H)-ones with Two Diversity Positions

“…The procedure described was later successfully used for the preparation of various hydroxyquinolinones – and represents the simplest and also the most widely applicable solution-phase synthesis known so far. In addition, in 2007 the first solid-phase synthesis of hydroxyquinolinone-carboxamides was published taking advantage of the same strategy.…”