Quinazoline derivatives substitution

Alkylthio, arylthio, and thioxo. The thioxo group in pyrimidine-2,4-dithione can be displaced by amines, ammonia, and amine acetates, and this amination is specific for the 4-position in pyrimidines and quinazolines. 2-Substitution fails even when a 5-substituent (cf. 134) sterically prevents reaction of a secondary amine at the 4-position. Acid hydrolysis of pyrimidine-2,4-dithione is selective at the 4-position. 2-Amination of 2-thiobarbituric acid and its /S-methyl derivative has been reported. Under more basic conditions, anionization of thioxo compounds decreases the reactivity 2-thiouracil is less reactive toward hot alkali than is the iS-methyl analog. Hydrazine has been reported to replace (95°, 6 hr, 65% 3deld) the 2-thioxo group in 5-hexyl-6-methyl-2-thiouracil. Ortho and para mercapto- or thio- azines are actually in the thione form. ... 

For example, Gyimesi-Forras et al. [50] performed a detailed investigation on the enantiomer separation of chiral quinazoline derivatives (2-substituted... 

Thermally promoted Claisen rearrangement of simple allyloxypyrimidines is difficult to effect, but is more common with quinazolines where it has been used to prepare allyl derivatives substituted in the carbocyclic ring < 1996HC(55) 1 >. An attempted amino-Claisen rearrangement of a 4-allylaminopyrimidine was unsuccessful <2005AJC368>. 

Substituted quinazoline derivatives can be prepared by thermal ring contraction of 3/7-1,4-benzodiazepines <1999H(51)2407>. Both 5-methoxy 981 and 5-diethylamino-3/7-l,4-benzodiazepines 983 have been converted to the analogous 4-substituted quinazolines 982 and 984. 

The pAj value for anhydrous quinazoline obtained using a rapid reaction apparatus is 1.95 at 20°C, as compared to the equilibrium pAf, value of 3.51 and to the pA, value of 7.77 for the hydrated species. The equilibrium pK value obtained by potentiometric titration or by spectrophotometry is a composite value arising from equilibrium between a stable hydrated cation and a stable anhydrous neutral species. Quinazoline in aqueous solution is a much stronger base (pAT = 3.51) than pyrimidine (pAT = 1.31) because its cation is stabilized as a covalent 3,4-hydrate. Most quinazoline derivatives in which the cation is capable of hydration are stronger bases than the corresponding pyrimidines. Substituents at the 4-position interfere with the covalent addition of water making the pK. values of 4-substituted quinazolines comparable with the pAf, values of the corresponding 4-substitiited pyrimidines (e.g., 4-methylquinazoline has pK 2.52, as compared to pK of 2.0 for 4-methylpyrimidine). The pAT values of several substituted quinazolines have been compiled. ... 

Regioselective lithiation on the benzene moiety of 4-substituted quinazolines occurs at position peri to the N1 ring nitrogen. Thus, treatment of 4-methoxyquinazolines 8 with an excess of lithium 2,2,6,6-tetramethylpiperidide (LTMP) at — 78 to 0 X followed by reaction with various electrophiles affords 8-substituted quinazoline derivatives 9. This regioselective lithiation provides easy access to a large range of substituted quinazolines which are not easily synthesized by other routes. ... 

V-Substituted-1,2,3,4-tetrahydroisoquinolin-l-ones (26) can be prepared in good yield by carbonyla-tion of A/-alkyl-o-bromophenefliylamines in the presence of catalytic amounts of Pd(OAc)2/PPh3. Similarly substituted 2-(2-bromoanilino)pyridines undergo carbonyl insertion to produce pyrido[2,l-b]quinazoline derivatives in good yield (equation S7). ... 

The presence of a substituted amino group at position 2 contributes to protonability and stabilization of the charge on the N whereas is not mandatory for activity [39], as supported in Table 1 by the data for abanoquil, a very potent but non subtype-selective a,-blocker, in conq)arison to its quinazoline analogue 1 [37], The modelling and QSAR for a series of quinazoline derivatives has recently been published [40],... 

The analgesic (5-ethoxy-2--dimethylaminomethyl-3-methylquinazoIin-4-one and 4,2 -thienyIquinazolines ), antithrombic and anticoagulant (2-vinyl-l,4-dihydroquinazolines), and antifibrillatory (l-aminoacyl-1,2-dihydroquinazolin-4-ones) action of quinazoline derivatives were patented, and 2-phenoxycarbonyloxymethyl-3-substituted-quinazolin-4-ones were potentially useful drugs for the treatment of arteriosclerosis. The effects of Quinazodine (118) as a cardiac stimulant and its hemodynamic... 

In practically all theories of the biosynthesis of quinazolines, anthranilic acid or an equivalent is regarded as one of the building blocks. Robinson 158) postulated that anthranilic acid (N-methylated where necessary), ammonia or amine, and formic acid or phenylacetic acid derived from phenylalanine units or their equivalents build up the simple substituted quinazoline derivatives. Thus vasicine (28) may be derived from anthranilic acid and proline, or closely related metabolites. Febrifugine (9) possibly could be formed from anthranilic acid, formic acid, ammonia, a Cj-unit, and lysine or equivalent compounds. For... 

Oripov et al. 199) reported on some reactions of 3-hydroxy- and 3-di-methylaminoformylidenepyrrolo[2,l-h]quinazoline derivatives. Karimov et al. 200,201) reported on the synthesis of methoxy- and oxy-substituted deoxy-vasicinones and deoxyvasicines. Some compounds derived from deoxyvasicinone showed fungicidal activity (202). The preparation of a specific antibody to deoxyvasicinone (33) for the immunoassay of A -pyrroline has been described by Sakamoto and Samejima 203). 

Substitution of 4-chloro- and 4-thiomethyl quinazoline derivatives occurs readily in the presence of a nucleophile to provide the corresponding 4-... 

Quinazoline derivatives were prepared by Fu and co-workers using an Ullmann-type coupling. Treatment of (2-bromophenyl)methylamine with benzamide in the presence of potassium carbonate and a copper(I) catalyst under thermal conditions in isopropanol gave the corresponding quinazoline in 87% yield. The authors also reported modest to good yields using several substituted (2-bromophenyl)methylamine and benzamide derivatives (not shown). 

Optically active trifluoromethyl-substituted tetrahydroimidazo[l, 5-c] quinazoline derivatives 44 were synthesized by Zhao and coworkers via a diastereo- and enantioselective Mannich-type cyclization cascade reaction of a-aryl isocyanoacetates and trifluoromethyl-substituted cyclic ketimines, using a multihydrogen-bonding donor squaramide/AgOAc cooperative catalytic system in THF at 0°C (Scheme 30) (140L4566). The products were obtained in 76—99% yield with a diastereomeric ratio of greater than 15 1 and 58-98% enantiomeric excess. 

Rohini R, Muralidhar Reddy P, Shanker K, Hu A, Ravinder V (2010) Antimierobial study of newly synthesized 6-substituted indolo[l,2-e]quinazolines. Eur J Med Chem 45 1200-1205 Antipenko L, Karpenko A, Kovalenko S, Katsev A, Komarovska-Porokhnyavets E, Novikov V, Chekotilo A (2009) Synthesis of new 2-thio-[l,2,4]triazolo[l,5-e] quinazoline derivatives and its antimicrobial activity. Chem Pharm Bull 57 580-585... 

Substituted-3-acylindoles have been prepared through the palladium-catalyzed carbonylative cyclization of 2 -alkynyltrifluoroacetanylides with vinyl triflates [102,106]. Analogously, the palladium-catalyzed cyclocarbonylation of bis(o-trifluoroacetamido-phenyl)acetylene 59 with vinyl halides and triflates afforded 12-acyUndolo[l,2-c] quinazoline derivatives in high yields. The palladium-catalyzed reaction of 59 with the vinyl triflates 60 at 50 ° C under 5 bar of carbon monoxide allowed the synthesis of the corresponding quinazoline derivative 61 in 98% yield (Scheme 9.29) [107]. 

---