Anilino-quinazolines

Figure 2.15 Scaffold-hopping from anilino-quinazolines (left) to cyano-quinolines...

Table 5.2 Fused anilino-quinazoline analogues are EGFR kinase inhibitors.

Morley and Simpson prepared quaternary salts from 4-phenoxy-quinazoline and 6- and 7-nitro-derivatives of 4-anilino- and 4-acet-amido-quinazohne. 6-Nitro-4-aminoquinazoline, however, could not be quatemized under the fairly mild conditions used by the... 

Quite similarly, the reaction product obtained from 2-benzylthio-3-phenylquinazolin-4(3H)-thione and hydrazine should be assigned the structure 2-anilino-3-aminoquinazoline-4(3//)-hydrazone instead of the reported 2-hydrazino-3-phenyl quinazoline-4(3//)hydrazone (Scheme III.23) (70IJC1055). 

The constitutionally isomeric 3-substituted (l//,3//)-quinazoline-2,4-diones and 2-phenylimino-4//-3,l-benzoxazin-4-ones are easy to distinguish via their El mass spectra (93RCM374). For quinazolinediones, the most striking feature is the loss of CO2, proving that a rearrangement due to anilino migration must occur. 

Anilino - 5a,8a - dihydro -1,3,7 - trimethyl - H- pyrrolo[3,4 - ( ]quinazoline- 2,4,6, (3H,5H,7H, 9Ef)-tetrones (94) were obtained in good yield by the sequential treatment of 5-formyl-1,3,6-trimethyluracil with (i) aniline to form the 6-methylene-5-(phenylamino)methylene derivative, via a [l,5]-hydrogen shift in the aldimine, and (ii) maleimide to achieve the central ring-forming cycloaddition reaction (Equation (53)) <90BCJ2938>. 

Wang and co-workers reported the intramolecular cyclocondcnsation of 2-anilino-3-aroylquinolines to quino[2,l-h]quinazolines <01TL2553>. Under basic conditions, compounds 94 cyclized to quinazolines 95 in excellent yields. 

An intimate mixture of anthranilonitrile and phenyl isothiocyanate heated to 100° whereupon a vigorous exothermic reaction takes place during a few min., and the product isolated after 12 hrs. at 100° 2-thio-4-anilino-l,2-dihydro-quinazoline. Y 97%. F. e., isolation of intermediates, and rearrangement of quinazolines, s. E. C. Taylor and R. V. Ravindranathan, J. Org. Chem. 27, 2622 (1962). 

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