Quinazolinone systems

A-Aminoaziridines are released from a quinazolinone system on reaction with hydrazine. 3-Acetoxyamino-2-trifluoromethylquinazolin-4(3//)-one is a source of the fV-aminonitrene. 

Hydration of nitriles Formation of the quinazolinone system from o-amido benzonitriles in one step is shown. 

Reduction of the pyrimidone ring in quinazolinone systems can be easily achieved. For example, hydrogenation of 110 under conventional conditions gave the hydroquinazolinone 111 as reported by Drizin and co-workers <01JMC1971>. 

Alkyl-3-aryl-4(3If)quinazolinones affect the nervous system in a... 

There are two important general types of reaction by which six-membered heterocycles containing two or more heteroatoms can be transformed into other six-membered heterocyclic systems, namely reactions which involve an ANRORC mechanism, and reactions which proceed by a Diels-Alder/retro-Diels-Alder type of mechanism. Transformation of 1,3-oxazinones and -thiazinones into pyrimidones (equations 193 and 194) has been extensively used, especially in the conversion of isatoic anhydride into quinazolinones (e.g. equation 195). 2,4-Diaryl-l,2,3,5-oxathiadiazines, which are readily accessible by reaction of sulfur trioxide with aryl isocyanates, are useful precursors to pyrimidines and 1,3,5-triazines (equation 196). 

Performing a Vilsmeier-Haack reaction on 3-benzoyloxy-2-methyl-quinazolin-4-one (184) afforded the isoxazolo[3,2- ]quinazolinone (185) [86IJC(B)709]. This ring system (187) was also synthesized by cyclocondensation of anthranilic acids or isatoic anhydrides with the isoxazolin-3-ones (186) (77AF766 83MIP1), or by condensation of methyl anthrani-late with 3-chloropropanoyl chloride followed by cyclization with hydroxylamine hydrochloride (77AF766). 

Naphtho[2, 3 3,4]-[l,2,5]triazocino[8,l+]quinazolinone 137 was obtained by refluxing of 2-substituted 3-amino-quizalin-4-one with 2,3-dichloro-l,4-naphthoquinone in DMF (Scheme 35 <2001MOL267>). Initial formation of 5,6-dihydrotriazocine derivative was followed by elimination of arylsulfinic acid and formation of ring system 137. 

Azonan-2-one easily forms cyclic imidate, which produced azonan-2-imine 178 (Scheme 36) <1996JME669>. On the other hand, its reaction with anthranilic acid led to the corresponding quinazolinone-type 6,6,9-ring system 179 <1996BML737>. 

An example of the separation of electronic effects that contribute to observed tt values in substituted quinazolinones has been described (113). It was found that the observed hydrophobic constant, irn, obtained from substituted quinazolinones can be correlated with the tt constant obtained from the phenozyacetic acid system (23, 24) and the Hammett o ... 

Although the yield in this synthesis of 2-quinazolinone is low, it provides a route to a 4-substituted ring system it deserves further study of its scope [3105]. 

One example of a successful application of solid-phase chemistry constitutes the highly versatile synthesis of quinazolinones 300/301 which efficiently combines an aza.-Wittig reaction with a multidirectional cyclisation cleavage. Iminophosphoranes were shown to be useful intermediates in organic synthesis, particularly for the preparation of different heterocyclic systems containing an endocyclic C,N double bond. In these cases, an aza-Mfrig-mediated anellation reaction was involved as the key step. 27-i29... 

The same authors have reported IR spectra of a number of quinazolinones. The ring system shows several characteristic absorptions in the region 1500-1700... 

In work previously cited <01BMCL211>, Corbett and co-workers reported an annulation onto the quinazolinone ring system. Treatment of 102 with 3-pyridyl acetylide generated in situ led to formation of adduct 103, which was then heated in POCI3 to provide a mixture of imidoyl chlorides 104. Heating the crude chlorides in a solution of thiourea in ethanol gave a 5-exo-dig cyclized product 105. 

The Bischler and Niementowski syntheses are the most important methods for the synthesis of quinazolines and quinazolinones, with the latter and more well-known reaction being m improvement on the Bischler synthesis. Additional methods for the synthesis of quinazoline and quinazolinone ring systems involve various rearrangement reactions and metal-mediated processes. Examples of these reactions are illustrated below. 

The synthesis of several commercially available and biologically significant quinazolines and quinazolinones are illustrated below. In most cases, the quinazoline or quinazolinone ring system is constructed from acyclic precursors and then functionalized accordingly. 

Pyridopyrimidinones of formulae lb (where W = S) and Ic (where W = NH) were significantly less active than the corresponding -propylthio and n-propylamino quinazolinones 2c and 2d. However, n-propoxy substitution generally gave higher activity than either n-propylthio or n-propylamino groups for a given heterocyclic system. 

A successful simple appHcation of the quinazolinone aimelation is the short step synthesis of rutecarpine 16, an indolopyridoquinazoline alkaloid of Evodia rutaecarpa, from 2,3,4,9-tetrahydro-lH-j8-carbolin-l-one 80 via 2-azidobenzoyl derivative 81 (Scheme 18) [222]. Even after Kametani s practical iminoketene/amides condensation synthesis [227,228], many other synthetic routes to 16 and related systems utilizing Fischer indole synthesis [223-225] or cyclocondensation [65,226,229,230], etc. have been developed among these syntheses, above quinazolinone annelation route is one of the most facile and concise one. Recently very concise Pd-assisted biaryl coupling route to 16 as well as to luotonin A (26) and B (27) has been developed by Harayama et al. [231,232] (see Sect. 3.5). 

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