An Antimalarial Alkaloid From Hydrangea. Xviii. Derivatives of 4-Pyrimidone

Abstract

4-Quinazolone, the aromatic moiety of the Hydrangea alkaloid (I), may be regarded as a 4-pyrimidone substituted on the 5 and 6 positions. In order to HO/X O ^\/CxNCHiiCOCHi CH \NZ H*2HC1 I investigate whether or not other 5,6-substituted pyrimidones, such as XI, would have desirable properties as antimalarials, the syntheses of a series of compounds of this type were initiated. As a class these compounds were unsatisfactory since the most active member of the series, the 5-phenyl derivative, XIa, had a low quinine coefficient of about 3 and the general method of synthesis (1) failed in many cases.1 Two types of substituents have been placed on the 5-position, aryl and alkyl. The aryl derivatives were synthesized from a-aryl-/3-alkyl-/3-methoxyacrylonitriles (II), readily obtainable from the appropriate benzyl cyanide (2), by condensation with thiourea to the 2-mercapto-4-aminopyrimidines (III). Desulfurization with hydrogen peroxide proceeded smoothly to the 4-aminopyrimidines (IV) and hydrochloric acid hydrolysis gave the desired 4-pyrimidols (Vila, b, and c). The intermediate, IVa, was prepared from benzyl cyanide, formamide, and ammonia at 170°a ccording to a method recently described (3).The 5-alkyl derivatives were synthesized by condensation of an appropriately substituted /3-keto ester (V) with thiourea to the 2-mercapto-4-pyrimidols (VI)followed by hydrogen peroxide desulfurization to the pyrimidols (Vlld, e, and f), a method of synthesis described for 5,6-dimethyl-4-pyrimidol (4). Both 5-aryland 5-alkyl-4-pyrimidols could be alkylated by treatment of their sodium salts with phenacyl bromide as shown by the formation of IXa and IXf2 from 5-phenyl-4-pyrimidol (Vila) and 5,6,7,8-tetrahydro-4-quinazolone (Vllf), respectively.Alkylation of the 4-pyrimidols (VII.) with the blocked alkaloid side chain, l-carbethoxy-2-(Y-bromoacetonyl)-3-methoxypiperidine (5), gave non-crystalline condensation products (VIII). Hydrolysis of these crude products with hydro- SUMMARYThe syntheses of two analogs of the Hydrangea alkaloid with the 4-quinazolone moiety replaced by 5-aryl-4-pyrimidones have been described.Pearl River, N. Y.

Synthesis of Bis-2,3-dihydroquinazolin-4(1H)-ones and 2,3-Dihydroquinazolin-4(1H)-ones Derivatives with the Aid of Silica-Supported Preyssler Nanoparticles

“…Furthermore, these compounds can act analogously to the antimitotic agent colchicine [6]. Additionally, these compounds can easily be oxidized to their quinazolin-4(3H)one analogues by Baker et al [7], which are themselves important biologically active heterocyclic compounds, Moore et al [8]. The usual procedure for the preparation of 2,3dihydroquinazolin-4(1H)-ones involves condensation of the appropriate derivatives of anthranilamide with an aldehyde or ketone using p-toluenesulfonic acid as a catalyst under vigorous conditions, by Ozaki et al [9].…”

Ascorbic Acid as an Efficient Organocatalyst for the Synthesis of 2‐Substituted‐2,3‐dihydroquinazolin‐4(1H)‐one and 2‐Substituted Quinazolin‐4(3H)‐one in Water

“…In particular, 2,3‐dihydroquinazolin‐4(1 H )‐one and quinazolin‐4(3 H )‐one have been used prepare various drug molecules . Because of its potential biological and pharmaceutical activities which may be antidepressant, analgesic, diuretic, sedative or antihistamine, it has received a vast domain of interest for the past many years.…”

[(N-Aryl)piperazinil]bythylpyrimidine derivatives with neurotropic and actoprotective properties

“…Конденсацией соединений V, VII, VIII с N-(δ-бром)бутиларилпиперазинами в диметилформамиде в присутствии безводного поташа с последующей обработкой продукта спиртовым раствором HCl в среде ацетона были получены гидрохлориды 1-6 и дигидрохлорид 7. Исходные соединения V и VII получали в условиях, описанных в [15][16], конденсацией производных ацетоуксусного III и малонового VI эфиров с мочевиной либо тиомочевиной или фенилтиомочевиной в соответствии со схемой 1 и 2. Изотиобрамин VIII был синтезирован по методике [12].…”