The quinazoline-2,4(1H,3H)-diones skeleton: A key intermediate in drug synthesis

Gheidari, Davood; Mehrdad, Morteza; Maleki, Saloomeh

doi:10.1016/j.scp.2022.100696

Cited by 9 publications

(4 citation statements)

References 74 publications

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“…Existing literature underscores the reactivity of the C4 position in aromatic nucleophilic substitutions of quinazolines I while achieving regioselective replacement at the C2 position poses challenges [ 11 ]. Modification of the C2 position of quinazolines requires longer time, higher temperatures, and sometimes the use of expensive transition-metal catalysts [ 12 ]. A selective C2 modification can be achieved by using 2-chloroquinazolines IV , where the C4 position is blocked by an unreactive C–C or C–H bond ( Scheme 1 ).…”

Section: Introductionmentioning

confidence: 99%

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

Līpiņš,

Jeminejs,

Ušacka

et al. 2024

Beilstein J. Org. Chem.

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2-Chloro-4-sulfonylquinazolines undergo functional group swap when treated with an azide nucleophile: 1) the azide replaces the sulfonyl group at the C4 position; 2) the intrinsic azide–tetrazole tautomeric equilibrium directs the nucleofugal sulfinate from the first step to replace chloride at the C2 position. This transformation is effective with quinazolines bearing electron-rich substituents. Therefore, the title transformations are demonstrated on the 6,7-dimethoxyquinazoline core, which is present in pharmaceutically active substances. The methodology application is showcased by transforming the obtained 4-azido-6,7-dimethoxy-2-sulfonylquinazolines into the α1-adrenoceptor blockers terazosin and prazosin by further C2-selective SNAr reaction and azide reduction.

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Section: Introductionmentioning

confidence: 99%

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

Līpiņš,

Jeminejs,

Ušacka

et al. 2024

Beilstein J. Org. Chem.

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“…Among the quinazoline and thienopyrimidine diones described in the literature, most of the compounds contain a substituent in position 3. The biological significance causes the emergence of a number of methods for the synthesis of 3-substituted quinazoline-2,4diones, including (i) the treatment of 2-aminobenzamides with phosgene, (ii) the reaction of isatoic anhydride with amines or isocyanates, (iii) the condensation of 2-halobenzoates with monoalkylureas, (iv) Baeyer-Villiger oxidation of 4-iminoisatins, (v) the three-component catalytic condensation of 2-haloanilines with CO 2 and isocyanides (Scheme 1) [49,50]. Instead of phosgene, various phosgene surrogates can be used as a carbonylating agent, including phenylisocyanate [51] or Troc-group [52].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 3-(Pyridin-2-yl)quinazolin-2,4(1H,3H)-diones via Annulation of Anthranilic Esters with N-pyridyl Ureas

Baykova

Geyl

Baykov

et al. 2023

IJMS

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A new route for the synthesis of quinazolin-2,4(1H,3H)-diones and thieno [2,3-d]pyrimidine-2,4(1H,3H)-diones substituted by pyridyl/quinolinyl moiety in position 3 has been developed. The proposed method concluded in an annulation of substituted anthranilic esters or 2-aminothiophene-3-carboxylates with 1,1-dimethyl-3-(pyridin-2-yl) ureas. The process consists of the formation of N-aryl-N′-pyridyl ureas followed by their cyclocondensation into the corresponding fused heterocycles. The reaction does not require the use of metal catalysts and proceeds with moderate to good yields (up to 89%). The scope of the method is more than 30 examples, including compounds with both electron-withdrawing and electron-donating groups, as well as diverse functionalities. At the same time, strong electron-acceptor substituents in the pyridine ring of the starting ureas reduce the product yield or even prevent the cyclocondensation step. The reaction can be easily scaled to gram quantities.

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“…This unique compound was first synthesized in 1858 by Heinrich Debus and attracted attention from researchers owing to its pivotal role in drug moieties. 1,2 The imidazole core forms the most important building unit of specific recognized components of cyanocobalamin, vitamin B7, histidine, adenine, guanine, and vital neurotransmitter bridges, such as histamine. 3 Moreover, imidazole is a part of medicines, such as omeprazole, methotrexate, and metronidazole endorsed by the FDA.…”

Section: Introductionmentioning

confidence: 99%

Construction of porphyrin-based photocatalyst comprising pyridinium ionic liquid moiety for the metal-free visible light-assisted N-arylation of amines: facile approach to afford drug intermediates

Mataghare,

Bhagat

2023

New J. Chem.

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The quinazoline-2,4(1H,3H)-diones skeleton: A key intermediate in drug synthesis

Cited by 9 publications

References 74 publications

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

Synthesis of 3-(Pyridin-2-yl)quinazolin-2,4(1H,3H)-diones via Annulation of Anthranilic Esters with N-pyridyl Ureas

Construction of porphyrin-based photocatalyst comprising pyridinium ionic liquid moiety for the metal-free visible light-assisted N-arylation of amines: facile approach to afford drug intermediates

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