Reactions with 2-aminonicotinic acid, I Some 8-aza analogs of quinazolinones and derived tricyclic compounds (original) (raw)
Related papers
MedChemComm, 2013
removal of the solvent in vacuo afforded the crude products 12a-b, which were purified by means of column chromatography on silica gel or recrystallization in ethanol. Synthesis of N-[(2-chloroquinolin-3-yl)methyl]-1-methoxy-3-(1-methyl-3-trifluoromethyl-1Hpyrazole-5-yloxy)propane-2-amine 12c General procedure: To a solution of 2-chloro-3-{[2-(1-methyl-3-trifluoromethyl-1H-pyrazole-5-yloxymethyl)aziridin-1-yl]methyl}quinoline 11b (1 mmol) in methanol (20 mL) was added boron trifluoride etherate (0.5 mmol, 0.5 equiv). After stirring for 20 h at reflux temperature, the reaction mixture was poured into water (30 mL) and extracted with dichloromethane (3 × 15 mL). The combined organic layers were subsequently dried over anhydrous magnesium sulfate. Filtration of the drying agent and removal of the solvent in vacuo afforded the crude product 12c, which was purified by means of column chromatography on silica gel. Synthesis of N-[(2-chloroquinolin-3-yl)methyl]-1-methoxy-3-(1-methyl-3-trifluoromethyl-1Hpyrazole-5-yloxy)propane-2-amine 12d General procedure: To a solution of 2-chloro-3-{[2-(1-methyl-3-trifluoromethyl-1H-pyrazole-5-yloxymethyl)aziridin-1-yl]methyl}quinoline 11b (1 mmol) in methanol (20 mL) was added boron trifluoride etherate (0.5 mmol, 0.5 equiv). After stirring for 1 h at 90 °C under microwave irradiation, the reaction mixture was poured into water (30 mL) and extracted with dichloromethane (3 × 15 mL). The combined organic layers were subsequently dried over anhydrous magnesium sulfate. Filtration of the drying agent and removal of the solvent in vacuo afforded products 12c and 12d, which were separated by means of column chromatography on silica gel. Synthesis of 1-[1-(quinolinylmethyl)aziridin-2-ylmethyl]-4-trifluoromethyl-1H-pyrimidin-3ones 13a-b The procedure for the synthesis of compounds 11a-c was applied for the preparation of 1-[1-(quinolinylmethyl)aziridin-2-ylmethyl]-4-trifluoromethyl-1H-pyrimidin-3-ones 13a-c. The crude products 13a-b were purified by column chromatography on silica gel. Synthesis of 4,5-dichloro-2-[1-(quinolinylmethyl)aziridin-2-ylmethyl]-2H-pyridazin-3-ones 14a-c The procedure for the synthesis of compounds 11a-c was applied for the preparation of 4,5dichloro-2-[1-(quinolinylmethyl)aziridin-2-ylmethyl]-2H-pyridazin-3-ones 14a-c. The crude products 14a-c were purified by column chromatography on silica gel or recrystallization from ethanol. Synthesis of 4,5-dichloro-2-{3-hydroxy-2-[(quinolinylmethyl)amino]propyl}-2H-pyridazin-3ones 15a-c The procedure for the synthesis of compounds 12a-b was also applied for the preparation of 4,5-dichloro-2-{3-hydroxy-2-[(quinolinylmethyl)amino]propyl}-2H-pyridazin-3-ones 15a-c.
Synthesis of New Quinazoline Derivatives
Heterocyclic Communications, 2004
New quinazoline derivatives were prepared by the reaction of 4-hydroxy-quinazoline with alkyl halides under phase transfer-catalysis conditions. The hydroxy group was readily converted into a thiol function by treating with phosphorus pentasulfide in pyridine and the subsequent alkylation of the thiol group was carried out under PTC conditions. Chlorination of 4-hydroxyquinazoline was carried out with phosphorus oxychloride. Branching of alkylamino side chains to the 4-OH, 4-S, and 4-C1 quinazolines has resulted in the synthesis of several compounds identified by 'H NMR. Introduction: Quinazoline derivatives have been reported to possess depressant, anticonvulsant and muscle relaxant properties as well as anti-inflammatory, antihypertonic, antibacterial, antifungal, analgesic and spasmolytic activities [1-6]. Attention was also drawn to this heterocyclic moiety with the aim to use it as possible pharmacophore, especially in case of tyrosine kinase inhibitors and adenosine antagonists [7]. Within the frame of our ongoing research devoted to chemosensitizers [8-11], we intended to prepare new derivatives belonging to this series. Results and discussion: At first, 4-hydroxy-quinazoline, 1_, was used as starting material. Alkylation was carried out under phase transfer catalysis (PTC) conditions with tetrabutylammoniumbromide (TBAB) as catalyst. In spite of the tautomeric equilibrium between N(3) and C(4), only small amounts of O-alkylated derivatives were identified but not isolated. Hence, substitution at the nitrogen atom in position 3 gave compounds 2 as the major product. Subsequently, the OH functional group was modified. On the one hand, the 4-thio-quinazoline 3 was prepared by treating 1 with phosphorus pentasulfide in pyridine. Alkylation of the thione only gave 4-alkylthioquinazoline derivatives 4 as already observed with thioacridines [12] or thioquinolines [13]. Dimers 5 were also prepared alkylating 3 with α,ω-alkyldihalides.
ChemInform Abstract: Synthesis of Linear Azolo- and Pyridoquinolines from Quinoline Derivatives
ChemInform, 2009
Angular N-tricyclic systems as triazolo [4,5-f]quinolines, triazolo[4,5-h]quinolines, imidazo[4,5-f]quinolines, imidazo[4,5h]quinolines were in the past obtained by connection of either f or h sides of the quinoline ring and both the adjacent carbon atoms of five-membered rings containing nitrogen atoms. Several attempts at obtaining the corresponding linear N-tricycles were made in the last century, but only the angular derivatives were obtained. Since 2000 a new simple pathway, involving suitable quinoline derivatives, which afforded the linear azolo and pyrido quinolines (imidazo[4,5-g]quinolines, triazolo[4,5-g]quinolines and pyrido[2,3g]quinoxalines) has been developed. Several linear N-tricyclic derivatives have shown some interesting pharmaceutical activity.
Chemical and Process Engineering Research, 2011
The 2-{[5-(2-Amino-4-oxoquinazolin-3(4H)-yl)-1,3,4-thiadiazol-2-yl]methyl}-1H-isoindole-1,3(2H)-dione 1 was synthesized and allowed to react with each of p-methoxybenzaldehyde, p-methoxyacetophenone and chloroacetyl chloride to produce the Schiff bases 2 and 3 and 2-chloro-N-(3-{5-[(1,3-dioxo-1,3-dihydro-2Hisoindol-2-yl)methyl]-1,3,4-thiadiazol-2-yl}-4-oxo-3,4-dihydroquinazolin-2-yl)acetamide 6, respectively. The products 2 and 3 were reacted with phenyl isothiocyanate to afford 4 and 5. Derivative 6 was reacted with various nucleophiles, namely: thioglycolic acid, ethyl glycinate and 2-aminoethanol giving 7-9 respectively. In turn, the derivative 8 was reacted with α-bromoglucose tetraacetate affording product 8a whereas 9 was reacted with p-acetylaminobenzenesulfonyl chloride affording derivative 9a. Moreover, the reactions of the derivative 6 with potassium thiocyanate, potassium cyanate, malonitrile, ethyl cyanoacetate and ammonium acetate gave derivatives 10-15, respectively. All the synthesized derivatives were confirmed by the IR, mass, 1 H-NMR and elemental analysis.
2011
The behavior of 2-ethoxy-4-chloroquinazoline 2 towards various nitrogen nucleophiles, namely: thiosemicarbazide, sodium azide, glucosamine, ethanol, and hydrazine hydrate has been discussed. Also, the behavior of 4-(2-ethoxyquinazolin-4-yl)thiosemicarba- zide towards one-carbon, for example, ethyl chloroformate, and two-carbon donors, for example, ethyl chloroacetate and diethyl oxalate has been investigated. On the other hand, new 5-ethoxy-2-substituted[1,2,4]-triazolo-[1,5-c]quinazoline derivatives have been obtained by ring closure accompanied with Dimroth rearrangement through the interaction of compound 2 with hydrazides of acetic, benzoic, crotonic, cinnamic, 2-furoic, and phthalimidoacetic acids. Structures of the novel products were confirmed by elemental, IR, MS, and 1H-NMR spectral analyses.
S�nthesis , Characterization , and Anti�In�a��ator� Acti�it� o� Newer Quinazolinone Analogs
2015
A series of 3-[2-(Substitutedbenzylideneamino)phenyl]-2-methyl-6-substituted quinazolin-4-ones (5–10), 3-[2-(3-chloro-2oxo-4-substitutedphenylazetidin-1-yl)phenyl]-2-methyl-6-substitutedquinazolin-4-ones (11–16), and 3-[2-(2-substitutedphenyl-4-oxo-1,3-thiazolidin-3-yl)phentl]-2-methyl-6-substitutedquinazolin-4-ones (17–22) have been synthesized in the present study.e structures of the synthesized compoundswere assigned on the basis of elemental analysis, IR, HNMR, andmass spectral data. All the newly synthesized compounds were screened for anti-in�ammatory and analgesic activities.
Synthesis of Novel Quinazoline Derivatives via Pyrimidine ortho-Quinodimethane
Molecules, 2002
The [4+2] cycloaddition between 2,4-diphenylpyrimidine ortho-quinodimethane and dimethyl acetylenedicarboxylate leads to 2,4-diphenylquinazoline-6,7-dicarboxylate (6). 2,4-Diphenylfuro[3,4-g]quinazoline-6,8-dione (7) is also obtained by basic hydrolysis of compound 6, followed by the closure of the resulting diacid in acetic anhydride.
Synthesis of some [1,2,4]triazino[5,6- b ]quinoline derivatives
Journal of Heterocyclic Chemistry, 2002
By coupling of diazonium salts with ethyl N- (4-oxo-1,4-dihydroquinolin-2-yl)carbamate 4, the corresponding 3-arylazocompounds 5 were obtained. These ones were cyclized thermally or in alkaline medium to the corresponding 2-aryl-2,3,5,10-tetrahydro- triazino [5,6-b]quinolin-3,10-diones 6. Compounds 6 were transformed by alkaline hydrolytic splitting to the corresponding 2-amino-3-arylazo-1,4-dihydroquinolin-4-ones 7. Starting carbamate 4 was prepared by a two-step synthesis from 2-amino-1,4-dihydroquinolin-4-one 1. The syntheses of condensed [1,2,4]triazines based on the cyclization of hydrazono-carbamates are advantageous in the cases when the starting compounds can be obtained by azo-coupling reactions with five membered aromatic heterocyclic compounds, e . g. at the synthesis of the pyrazolo[3,4-e][1,2,4]triazines [2], [1,2,4]triazinoindoles [3,4] or [1,2,4]triazines with condensed furan [5,6] or thiophene ring [7].
ChemInform, 2007
4-Hydroxy-1-methyl-3-[E-3-(4-oxo-4H-chromen-3-yl)acryloyl]quinolin-2(1H )-one (3) was smoothly obtained via a one-pot aldol dehydration reaction of 3-acetyl-4-hydroxyquinolin-2(1H)-one with 3-formylchromone and was utilized to prepare miscellaneous triheterocyclic systems containing the quinolinone moiety. Both the a,b-unsaturated ketone side chain and the g-pyrone ring in compound 3 were subjected to nucleophilic cyclization with certain 1,2-and 1,3-bifunctional N,N-, N,O-, N,C-, and O,C-nucleophiles under different reaction conditions. Many pyrazolinyl-, isoxazolinyl-, pyrimidinyl-, and pyridinylquinolinones bearing other six-or five-membered heterocyclic systems have been conveniently synthesized using more than one synthetic route. 330 b-proton is considerably shifted to d ¼ 9.24 as doublet (J ¼ 16 Hz). The structure is assuming E-form, which suffers anisotropic effect due to the neighboring C5 5O of chromone system.