4-Aminoquinazoline , synthesis quinazolines

The linearly fused benzologues, pyrimido[2,l-A]quinazolines, are most frequently synthesized from a 2-amino- or 2-iminoquinazoline. Synthesis from [6+0] atom fragments by bond formation 7 to the ring junction nitrogen takes place when the 2-aminoquinazoline bearing a suitable substituent at N-3 is cyclized. The 2-iminoquinazoline-3-propionates 197 cyclized on treatment with alkali to give 198 (Scheme 31) <1997EPP0778258>. 

The 2,3-dihydro-6/7-pyrimido[2,l-A]quinazolin-4(177)-ones 201 were obtained in a one-pot synthesis from the iminophosphorane 199 and isocyanate, through the 2-aminoquinazoline 200. Yields were good (R1 = H, Rz = c-hexyl) to excellent (R1 = Rz = Ph) (Equation 21) <1996TL9071>. 

Cyclization of 3-aminoquinazoline-4-thiones (375) with carbon disulfide gave the zwitterionic l,3,4-thiadiazolo[3,2-c]quinazoline (376) (771JC(B)1110]. Synthesis from properly functionalized 1,3,4-thiadiazole precursors was also reported [83JCS(P1)2011], according to which the 2-(2-nitrophenyl)-l,3,4-thiadiazoles (377) were reduced and cyclized to 378. 1,3,4-Thiadiazoloquinazolines were shown to exhibit amebicidal... 

Synthesis according to the first approach requires quinazoline precursors with an appropriate subtituent on position 2 or 3 which, upon cyclization, forms the terminal pyrimidine ring. Thus, 2-aminoquinazolin-4(3//)-one (505) underwent cyclization with a,j8-unsaturated acids (78KGS105 80MI1) or their chlorides (87KGS1527) to the pyrimido... 

A similar rapid microwave one-pot synthesis of substituted quinazolin-4-ones was also reported, which involved cyclocondensation af anthranilic acid, formic acid (or an orthoester) and an amine under solvent-free conditions (Scheme 3.37)61. A complimentary approach was adopted to synthesise 4-aminoquinazolines in very good yields, involving the reaction of aromatic nitrile compounds with 2-aminobenzonitrile in the presence of a catalytic amount ofbase (Scheme 3.38)62. The reactions were performed in a domestic microwave oven and required only a very short heating time. A microwave-assisted synthesis of a variety of new 3-substituted-2-alkyl-4-(3H)-quinazolinones using isatoic anhydride, 2-aminobenzimidazole and orthoesters has also been described (Scheme 3.38)63. 

Cyclocondensation routes also provide access to pyrimidines. 2,3-Disubstituted pyrido[2,3-/i]-quinazolin-4(3//)-ones are obtained via cyclocondensation of 5-aminoquinoline-6-caiboxylic acid with acid chlorides <02SC235>. 5,6,8-Trialkyl-7-methoxy-2-aminoquinazolines are obtained from 1,3-dimethoxybenzenes via cyclocondensation of intermediate dihydrobenzenes with guanidine carbonate <02TL3295>. Diastereoselective intramolecular hetero Diels-Alder cyclization of a pyrazole carboxaldehyde condensed onto 1,3-dimethylbarbituric acid (101) gave polycyclic heterocycle 102 <02T531>. An efficient one-step synthesis of cyclobutene-annelated pyrimidinones 103 from methyl 2-chloro-2-cyclopropylideneacetate and amidines has been... 

Acetates 5 with an acyl group at position 6 react with amidines, guanidine, C9-alkylisoureas, and 5-alkylisothioureas, respectively, in ethanol to give quinazolin-5-ols 6 in good yields. The synthesis is successful only with 2- and 4-substituted acetates and is especially useful for the preparation of 2-methoxy-, 2-(methylsulfanyl)-, and 2-aminoquinazolin-5-ols." ... 

A study of all the stages in the synthesis of 4-aminoquinazolines from isatoic anhydride, via anthranilamide and o-aminobenzonitrile, made possible the preparation of these compounds by a one-pot synthesis. The anhydride was treated with ammonia in dimethylformamide, nitrogen was then bubbled through the solution to remove excess of ammonia, phosphoryl chloride was added and heated at 40°-60°C for conversion into the nitrile, and finally the respective amine was added to yield the 4-(substituted-amino)-quinazolines in 44-79% yields. ... 

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