Cyclic hydroxamic acids derived from quinazoliue

Schapira, Celia B.; Lamdan, Sámuel

doi:10.1002/jhet.5570090318

Cited by 9 publications

(6 citation statements)

References 15 publications

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“…On the other hand, quinazolinone benzoate 4a (3a and 4a were confirmed by X-ray crystallography, see the ESI †) was isolated in a significant amount. This unexpected result provided a straightforward approach to synthesize cyclic hydroxamic esters derived from quinazoline, 12 which are a series of important heterocyclic compounds in drug discovery. For example, 4a analogues had been identified as novel inhibitors of Mycobacterium tuberculosis acetohydroxyacid synthase (MTB-AHAS).…”

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confidence: 96%

Copper-catalyzed oxidative coupling between quinazoline 3-oxides and unactivated aldehydes: an efficient approach to functionalized quinazolines

et al. 2016

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Copper-catalyzed oxidative coupling between quinazoline 3-oxides and unactivated aldehydes: an efficient approach to functionalized quinazolines

et al. 2016

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“…It is devoid of N-OH group (negative FeCl 3 color test). 5 The UV spectrum showed two absorption maxima at l max = 327.7 nm and 266.7 nm, respectively and appeared as a combination spectrum of 2-phenylindole (328 nm) and quinazolin-4(3H)-one (265 nm) rings. 6,7 The presence of indole moiety was further evident from the signals at d = 6.6 (s, l H, 3-H) and 7.95 (NH, D 2 O exchangeable).…”

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Synthesis of Indolylquinazolinone: A Novel Bisazaheterocycle

Reddy¹,

Reddy²,

Reddy³

2000

Synthesis

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A facile synthesis of 2-(2-aryl-1H-7-indolyl)-3,4-dihydroquinazolin-4-ones is reported.Our interest in developing quinazolinone based heterocycles prompted us to react 2-(2-aminophenyl)-3-hydroxyquinazolin-4(3H)-one (3) with aralkyl ketones. The aim was to isolate quinazolino[3,2-d][3,1,4]benzoxadiazepin-9-ones (4) by bridging with carbon the N-hydroxyl and amino groups in 3. But surprisingly the reaction yielded 2-(2-aryl-1H-7-indolyl)-3,4-dihydroquinazolin-4-ones (6), providing a facile synthetic route for the less known indolyl quinazolinones which are anti-inflammatory, psychotrophic agents, 1,2 CCK receptors 3 and CNS active as well as depressant agents. 4The cyclic hydroxamic acid 3 was prepared in one-step from 2-aminobenzhydroxamic acid (1) and isatoic anhydride (2). Refluxing an equimolar mixture of 3 and 4-methylacetophenone in nitrobenzene for 6 hours, followed by usual workup yielded a crystalline solid (M + at m/z 351) (Scheme 1). It is devoid of N-OH group (negative FeCl 3 color test). 5 The UV spectrum showed two absorption maxima at l max = 327.7 nm and 266.7 nm, respectively and appeared as a combination spectrum of 2-phenylindole (328 nm) and quinazolin-4(3H)-one (265 nm) rings. 6,7 The presence of indole moiety was further evident from the signals at d = 6.6 (s, l H, 3-H) and 7.95 (NH, D 2 O exchangeable). On adding D 2 O, the 3-H signal shifted to downfield (d = 6.8), a characteristic feature of indoles. 8 The appearence of a doubly charged ion peak (at m/z 176) is also reminiscent of indoles. 9The quinazolinone moiety revealed itself by the appearence of CO peak (n = 1702 cm -1 ) in the IR spectrum and the peri-proton signal as doublet at d = 8.2 in the 1 H NMR spectrum. The 13 C NMR spectrum revealed a total of 19 different carbons including quinazolinone carbonyl (d = 156.9), azomethine carbon (d = 153.3) and C 3 of indole (d = 108.6).The reaction was extended to six other aralkyl ketones (Scheme 1), and in each case the corresponding 2-(2-aryllH-7-indoyl)-3,4-dihydroquinazolin-4-one was isolated and characterized. As expected, there is no peak around d = 6.6 in the 1 H NMR spectra for the products obtained with propiophenone and dibenzyl ketone, to confirm that C 3 of indole carried substituents in 6f and 6g (see experimental scetion).The mechanism of formation of 6 is both interesting and intriguing (Scheme 2). We presume that the reaction proceeds via a transient quinazolino [3,2-d][3,l,4]benzoxadiazepin-9-one 4 and 2-(2-oxirinylaminophenyl)quinozolin-4(3H)-one 5. Intramolecular oxygenation of C=N in cyclic hydroxamic acids was reported earlier from our laboratories. 10 Scheme 2 Scheme 1Downloaded by: University of Pittsburgh. Copyrighted material.

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“…Contrary to all expectations, however, the annelation of a pyrimidine ring presented numerous difficulties. Treatment of 9 with guanidine in refluxing methanol-sodium methoxide did not lead to the expected 2,4diaminopteridine, but rather to intermediate 10, Heating 10 in refluxing dimethylformamide, however, did give 11, which was finally converted to 2,4-diamino-6-methyl-8hydroxy-7(8/i)-pteridinone (2a) hemihydrate by suspension in water followed by careful acidification. The water of hydration in 2a proved extremely difficult to remove.…”

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confidence: 98%

“…As anticipated, the 6-chloro substituent of 7 proved to be extremely reactive to nucleophilic displacement, since it is both ortho to the A7-oxide grouping and para to the nitrile substituent. Thus, treatment of 7 with 0.5 N sodium hydroxide led to a separable mixture of the carboxamide derived from 7 (i.e., 8) and l-hydroxy-2-amino-3-cyano-5methyl-6(lH) -pyrazinone (9) (see Scheme II factory was the hydrolysis of 7 in 95% acetic acid to give only 9 in 82% yield. This appeared to be an ideal intermediate for eventual conversion to the desired pteridine hydroxamic acid (2a).…”

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confidence: 99%