Quinazoline ring system

Lemus, R. L. Skibo, E. B. Studies of extended quinone methides. Design of reductive alkylating agents based on the quinazoline ring system, j. Org. Chem. 1988, 53, 6099-6105. 

This method has been applied to a large-scale preparation of 6-bromoindole, which reacts with various arylboronic acids via the Suzuki reaction to afford 6-arylindoles (Eq. 10.50).64 6-Bromo-5-methoxyindole for use in the synthesis of marine bromoindole65 and 5-amino-7-ethoxycarbonylindole for use in synthesis of l//-pyrrolo[3,2-g]quinazoline ring system (Eq. 10.51)66 have been prepared from the appropriate o-nitrotoluene. 

It is not unusual to find that some of the various possible structures of a particular heterocyclo-quinazoline ring system have not been synthesized. The absence of some of these possible structures in this review indicates that, to the best of our capability, they have not been synthesized as yet. 

The quinazolinocarboline alkaloids, as the name indicates, contain both carboline and quinazoline nuclei. The first known representatives were rutaecarpine and evodiamine, and two more representatives have been encountered more recently. Rhetsinine, which was at one time regarded as belonging here, is included in this chapter because of its affinity with rhetsine, though it does not contain the quinazoline ring system. This chapter is a summary and an extension of that dealing with these alkaloids in Volume II, p. 402. 

Another ring forming reaction uses an initial epoxide opening by the amine of an amino alcohol to generate a ring opened product which was subsequently converted to a quinazoline ring system <07JOC1492>. 

Amidines 14 are cyclized to quinazolines 15 in lithium alkylamide or dialkylamide mediated reactions in which the construction of the quinazoline ring system and introduction of the amino substituent occur in the same reaction. Mechanistically, each fluorine of the trifluo-romethyl substituent of the amidine is displaced by a series of internal nucleophilic processes and the resulting quinazoline contains the amino function of the lithium reagent incorporated at the C4 position. The cyclization method is suitable for the synthesis of sterically congested quinazolin-4-amines and in syntheses of derivatives for which the corresponding chloroquinaz-olines are not readily available. ... 

Varano F, Catarzi D, Colotta V et al (2008) Novel AMPA and kainate receptor antagonists containing the pyrazolo[l, 5-c]quinazoline ring system Synthesis and structure-activity relationships. Bioorg Med Chem 16 2617-2626... 

Quinazolinamines with the amino groups in the heterocyclic ring are prepared by the same sort of reactions as reviewed for pyrimidines. Amination, by way of electrophilic substitution, for example, by nitration or nitrosation in the carbocyclic ring, is substituent dependent and may have to be carried out in a precursor before formation of the quinazoline ring system. 

The angular pyrimido[l,2-c]quinazoline ring system has also been prepared in other ways. Thus... 

Chlorosulphonation of 4 -chloro-o-acetotoluidine yields the eorresponding sulphonyl chloride derivative whieh on amination forms the sulphonamide derivative. Oxidation of the methyl moiety gives the respeetive anthranilamide derivative whieh on hydrolysis eliminates the acetyl group to yield the substituted anthranilic acid. Fusion of this amino acid with propionamide first gives rise to an intermediate by the loss of a mole of water and ultimately helps in the closure of the ring to generate the quinazoline ring system. Catalytic reduction of this finally produces the official compound. 

The mass spectra of both alkaloids show that the tetrahydropyrido-quinazoline ring system is particularly stable. The molecular ion, m/z 200, is the base peak in the spectrum of (61) and the only major fragment (85% of the base peak) is at m/z 199, due to loss of a hydrogen radical and formation of a stable ion. In the mass spectrum of (62), the M-1 ion, m/z 185, is the base peak, and the molecular ion, m/z 186 (85% of the base peak), is the only other major peak found. 

Thiazolo[2,3- ]qi]inazolines [CsNS-C Ng-Ce].— Annelation of a thiazole ring to the quinazoline ring system may be carried out by standard procedures. Ester (123) reacts normally with hydrazine or phenylmagnesium bromide, but undergoes a complex rearrangement with piperidine or iV-methylpiperazine. ... 

Staskun, B. and Wolfe, J. E, New approach to the Indolo(2,l-fo]quinazoline ring system by cycliza-tion of 3(o-chlorophenyl)-2-methyl-4(3Ff)quinazolinone and its m-isomer synthesis of the antibiotic tryptanthrin, S. Afr. J. Chem., 45, 5,1992. 

---