Quinazoline, 4-methyl-. reaction with

Thiation of [l,2,4]triazino[3,2-h]quinazoline-3,10-dione 782 with phosphorus pentasulfide in pyridine proceeded selectively to give the 3-thioxo analogue 783. The latter was converted to the corresponding 3-methylthio derivative 784 by reaction with methyl iodide. Treatment of 784 with hydrazine gave 785, which was converted to 786 and 787 by cyclization with formic acid or carbon disulfide (90JHC591). Cyclization of 785 with sodium nitrite in hydrochloric acid gave 788 (90JHC591). 

A series of 6- and 7-aciylamide derivatives of 4-(phenylamino)-quinazoline and 4-(phenylainino)-pyridopyrimidine, classes of epidermal growth factor receptor (EGER) inhibitors, have been prepared from the corresponding amino compounds by reaction with actoyl chloride/base <99JMC1803>. Reaction of thionyl chloride with hexahydro-7-methyl-pyrimido[l,6-a]-pyrimidine-6,8-dione yields the corresponding 9,9 -thiobispyriiiudopyrimidine derivative <99JHC453>. 

Reaction of anthranilonitrile or methyl anthranilate with 3-hydroxy-2-butanone followed by malononitrile gave the pyrrolo [1,2-a] quinazoline 16 (79AP552). Both of the diazine and azole rings of pyrroloquinazolines were also simultaneously formed by cyclization of the anilide 17 derived from 3-chloropropionic acid and 2-aminobenzophenone with potassium cyanide to afford the pyrrolo [1,2-a] quinazoline 18 (68JHC185 71USP3595861). 

Whereas the reaction of small primary amines with 2-(chloromethyl)quinazoline 3-oxides 1 leads to ring-enlarging rearrangement to 1,4-benzodiazepines (cf. p 159), weak primary amines.secondary amines, hydroxylamine, thiolates, " thiocyanate. cyanide, and the carbanions of nitroethane and nitropropane lead only to products 2 derived from substitution of the halogen. In a few cases, also in the reaction of 2-(chloro-methyl)quinazoline 3-oxides with methylamine, the unrearranged 2-[(methylamino)methyl]-quinazoline 3-oxide products are isolated. " ... 

Racemic tryptophan similarly gave 4,/-12, the methyl ester and 2-methyl derivatives gave the corresponding quinazolines, but the JV-acetyl derivative failed to yield a quinazoline and gave AT-acetyl-iV -formylkynurenine. Clearly the pyrrole ring was cleaved, and then reaction with ammonia followed by ring closure, gave the quinazoline. This is probably how the metabolism of tryptophan takes place in the quinazoline pathway in Pseudomonas (see Section VIII). 

The cyclization of o-ureidobenzoic esters to quinazoline-2,4-diones and 4-one-2-thiones, respectively, in aqueous alkali proceeded equally well with the N-hydroxy urea (X = O) and thiourea (X = S) esters 28. If the reagents were altered to triethylamine in pyridine the 2,l-benzisoxazol-3-ones were formed. Ethyl o-hydroxyaminobenzoate reacted with two molecular equivalents of methylisocyanate in ethanolic alkali and gave 3-methyl-l-methyl-aminocarbonyloxyquinazoline-2,4-dione. When three molecular equivalents were used the tricyclic quinazoline 29 was obtained. A similar reaction with methylisothiocyanate did not behave in the same way, and 3-methylquina-zolin-4-one-2-thione was formed. It was shown that the intermediate 1-hydroxy derivative (30) gave 3-methylquinazolin-4-one-2-thione, i.e., loss of the 1-oxygen atom, on further treatment with methylisothiocyanate in the presence of triethylamine. The preparation of quinazoline-2,4-diones by... 

Methylation reactions (N versus S) of 2-thiophenobarbital under various conditions have been performed [94MI(68)117]. There is also a report on the ratio of N- and 6>-alkylation of 4(3/7)-quinazolinones depending on the nature of a substituent in position 2 [93CPB(41)1114].. Quinazoline-2,4(l//,3W)-d ones have been alkylated with l,4-dibromo-2-methylbut-2-ene under phase-transfer conditions to give dialkylated as well as monoalkylated products [93JHC(30)lil71. 

Same reaction has also been carried out with methyl iodide in place of amine and in the presence of sodium hydride to yield N-methyl-3,4-dihydropyrazino[2,l-b] quinazolin-6-ones. The novel pyrimido[4,5-d]pyrimidine derivatives of biological significance from electron rich 6-[(dimethylamino)methylene]amino uracil undergoes [4+2] cycloaddition reactions with various in situ generated glyoxylate imine and imine oxides, after elimination of dimethylamine from the (1 1) cycloadducts and oxidative aromatization. This method provides a suitable method for the direct synthesis of pyrimido[4,5-d]pyrimidines in excellent yields, when reaction was carried out in the solid state and under microwave irradiations (Prajapati et al., 2006). 

S-oxide. The reaction of quinazoline with hydroxylamine is not hindered by the presence of a 4-substituent since 4-methyl-quinazoline also gives 4-methylquinazoline 3-oxide with hydroxyl-... 

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