Quinazoline 3.4- dihydro

Phosphorane Phosphoramidate Phosphorothioate Phthalocyanine Porphyrin Pyran Dihydro Pyrazole Pyridine Dihydro Pyrimidine Dihydro Pyridinium Salt Pyridinium Ylide Pyrrole Pyrrolidine Pyruvic Amide Quinazoline Dihydro... 

Refluxing, 5.6-dihydro-7H-thiazolo[3,2-a]pyrimidine-7-one (370j with isopropylamine led to 2-imino-3-[2-(isopropylaminocarbonyl)ethyl]-thiazoline (371) (108). Similarly. tetrahydrobenzothiazolo[3,2-fl][2.3-f>]-quinazoline is opened by potassium hydroxide, yielding 373 (Scheme 214)... 

The least troublesome routes to 3,4-dihydro- and 1,2,3,4-tetrahydro-quinazoline are probably the reduction of quinazoline by sodium borohydride, in water for the former or in methanol for the latter. Both must be isolated as salts. The dihydroquinazoline may be formed also by reduction with LAH in ether (65JHC157). In contrast, 5,6,7,8-tetrahy-droquinazoline is best made by primary synthesis from 2-formylcyclohexanone and for-mamide (57CB942) or from cyclohexanone and trisformamidomethane (60CB1402). 

Reduction of quinazoline with hydriodic acid gives 3,4-dihydro-quinazoline but this can be achieved more satisfactorily by catalytic means. With palladium-charcoal it was found possible to reduce quinazoline to 1,2,3,4-tetrahydroquinazoline. ... 

Catalytic reduction of quinazolines unsubstituted in position 4 using palladium-charcoal, palladium on calcium carbonate, Raney nickel, or Adam s platinum has been used for preparing 3,4-dihydro-... 

Dihydroquinazolines are normally stable compounds but they deteriorate on long standing. Some examples are known to oxidize to the corresponding 4(3H)quinazolinones. 3-Methyl-3,4-dihydroquin-azoline is converted to the 4-oxo compound after three recrystallizations from light petroleum. The most remarkable example is 3,4-dihydro-6-fluoro-3(p-fluorophenyl)quinazoline [(44), R = F] which oxidizes at its melting point (137°-I38°C), Other halogenated derivatives of (44) are more stable. ... 

However, much greater differences between the spectra of dihydro compounds and the corresponding covalently hydrated species are sometimes found. Thus, the neutral molecule of hydrated quinazoline,... 

The structures of 5-ethyl-1 ]-methyl-9-oxo-5,l l-dihydro-9/7-pyrido[2,1-6]-quinazohne-8-carboxylic acid (00K669), the chromophore 4 of isopyoverdin siderophores (01T1019), and that of 5,5n,6,7,8,9-hexahydro-l l//-pyrido [2,]-6]quinazoline (99SL1383) were justified by X-ray analysis. 

The reaction of methyl anthranilate and 3-amino-2-chloropyridine in 1,2,4-trichlorobenzene in the presence of KOt-Bu at 50 °C gave 5,1 l-dihydro-6//-pyrido[2,3-Z)]benzodiazepin-6-one and 6-amino-ll//-pyr-ido[2,l-Z)]quinazolin-l 1-one as a by-product (99BMCL3031). 

Reaction of 2-amino-3-hydroxypyridine and cyclohexanone 433 in boiling AcOH yielded N, 1 -diphenyl-6-hydroxy-3-methyl-11 -0x0-1,2-dihydro-11 //-pyrido[2,l-Z)]quinazoline-2-carboxamide (434) (98MI2, 99USP5908840, 99USP5914327). 

Reduction of 2,3,6,7-tetrahydro-177,5i/-pyrido[3,2,l-//]quinazoline-l,3,7-trione and 7-chloro-6-formyl-2,3-dihydro-177,5i/-pyrido[3,2,1 -(/]quinazo-line-l,3-dione with NaBH4 in THF in the presence of 60% aqueous solution of NaOH gave 7-hydroxy and 7-chloro-6-hydroxymethyl derivatives, respectively (01MI28). 

Vilsmeyer-Haack formylation of 7-hydroxy-2,3,6,7-tetrahydro-l//,5//-pyrido[3,2,l-y]quinazoline-l,3-dione with POCI3/DMF gave 7-chloro-6-formyl-2,3-dihydro-l//,5// derivative. Boiling a toluene solution of the aforementioned 7-hydroxy derivative in the presence of pTSA yielded dehydrated 2,3-dihydro derivative (01MI28). 

Fluoro atom of 2-amino-8,9-difluoro-5-methyl-6,7-dihydro-5//-pyr-ido[3,2,l-y]quinazoline-l,3-dione was replaced by 3-substituted pyrrolidines in the presence of NEt3 in DMSO at 110°C for 18h (01MIP23). 

Treatment of pyrimidine-2-thione 193 with AICI3 in PhN02 yielded 2-(4-benzylphenyl)-6-oxo-6,7-dihydro-4//-pyrido[6,l-a]isoquinolin-4-thione (194) (98MI47). Cyclization of l-(2-carboxyethyl)-l,2,3,4-tetrahydroquina-zoline-2,4-dione (195) in PPA afforded l,2,3,5,6,7-hexahydropyrimido[3,2, l-//]quinazoline-l,3,7-trione (196) (97CHE96). 

Phenyl-5,6-dihydro-l//,7//-pyrido[3,2,l-//]quinazoline-7-one and 1,7-dione 179 (X = H2 and O) were prepared from tetrahydroquinolines 206 and 207 with A-(ethoxycarbonyl)thiobenzamide and PhCOCl, respectively (98EJM763). 

BuOK. (15.4 g, 0.139 mol) was added in portions to 6-chloro-2-(chloromethyl)-4-phenyl-l,2-dihydro-quinazoline 3-oxide (11a 42.2 g, 0.137 mol) in THF (700 mL), cooled in acetone/solid carbon dioxide, and the mixture was stirred for 4.5 h as it warmed to 20 C. It was filtered through Celite, the filtrate was evaporated under reduced pressure and the residue was recrystallized (benzene/hexane) to give the crude aziridinoquinazoline oxide 12a yield 22.Og (57%) mp 135-136.5 C. 

Another dihydro derivative has been described in connection with medicinal chemical studies. Thus, reaction of 2-(chloromethyl)quinazoline-3-oxide (3) with hydrazine gives hydr-oxytriazocinamine 4 (and not a diazepine derivative as originally assigned), vigorous acetylation of which results in a rearrangement to give oxazolotriazocine 5.10... 

Triazinoindole 146 was obtained (74T3997) in a mixture with quinoline 148 on thermolysis or of 3-(alkylthio)-6,7-dihydro[l,2,4]triazino[l,6-c]quinazolin-5-ium-l-olate 144 acid hydrolysis. The reaction presumably took place via the decomposition of 144 to a ketone and 142, which then cyclized. Compound 144 was prepared by the condensation of 142 with aldehydes, ketones, or their equivalents. Reaction of 142 with 3-amino propanol gave 143, which cyclized to 145 and then to 147 with base [80ACH(104)107] (Scheme 32). 

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