Quinoline 2-chloro-4-methyl

Among the aromatics, it was found that 4-nitroquinoline N-oxide [56-57-5] is a powerful carcinogen producing malignant tumors when painted on the skin of mice (80). It was further estabUshed that the 2-methyl, 2-ethyl, and 6-chloro derivatives of 4-nitro quinoline oxide are also carcinogens (81). 

Quinoline, 6-amino-protonation, 2, 341 Quinoline, 7-amino-protonation, 2, 341 Quinoline, 8-amino-alkylation, 2, 179 methylation, 2, 342 Quinoline, 4-amino-7-chloro-as antimalarial, 2, 517 Quinoline, 2-amino-3-cyanotetrahydro-synthesis... 

Chloro-oxazolo[4,5-/i]quinoline-2-carboxylic acid methyl ester was the most active compound in tests for inhibitors of antigen-induced release of histamine in vitro from rat peritoneal mast cells (IC50 of 0.3 p,M) and as inhibitors of IgE-mediated passive cutaneous anaphylaxis in the rat (ED50 (intraperitoneal) of 0.1 mg/kg in dose 0.5 mg/kg as an inhibitor of the test)—10 times and 60 times more potent, respectively, than the disodium salt of cromoglycic acid (85JMC1255). 

Linearly annelated 2-methyl-4,9-dioxo-4,9-dihydrooxazolo[4,5-g]quinoline 14 was prepared in 31% yield by cyclization of 6-acetamido-7-chloro-5,8-dioxo-5,8-dihydroquinoline in acetic anhydride and sulfuric acid (59LA108). 

Acetylation of 6-amino-7-chloro-5,8-quinolinedione and subsequent replacement of the chlorine atom to a -SH and then a -SMe group gave the final linear 2-methyl-4,9-dioxo-4,9-dihydrothiazolo[4,5-g]quinoline 40 (59LA108). 

Chloro-1 -methyl-5-phenyl-s-trizolo[4,3-a]quinoline A stirred mixture of 6triethyl-orthoacetate (0.925 g,0.0057 mol) and xylene (100 ml) was refluxed, under nitrogen, for 2 hours 40 minutes. During this period the ethanol formed in the reaction was removed by distillation through a short,glass helix-packed column. The mixture was concentrated to dryness In vacuo and the residue was crystallized from methanol-ethyl acetate to give 1.28 g of 7-chloro-1-methyl-5-phenyl-s-triazolo[4,3-a]-quinoline (83.9% yield). The analytical sample was crystallized from methylene chloride methanol and had a melting point 252.5°-253.5°C. 

Chloro-2-(3-methyl-4H-1,2,4-triazol-4-yDbenzophenone (Oxidation of 7solution prepared by adding sodium periodate (2 g) to a stirred suspension of ruthenium dioxide (200 mg) in water (35 ml). The mixture became dark. Additional sodium periodate 18 g) was added during the next 15 minutes. The ice-bath was removed and the mixture was stirred for 45 minutes. Additional sodium periodate (4 g) was added and the mixture was stirred at ambient temperature for 18 hours and filtered. The solid was washed with acetone and the combined filtrate was concentrated in vacuo. The residue was suspended in water and extracted with methylene chloride. The extract was dried over anhydrous potassium carbonate and concentrated. The residue was chromatographed on silica... 

Chloro-/3-(trifluoromethyl)acroleins reacted with 2-aminothiophenol at room temperature to give a mixture of a benzothiazole and quinoline. This was in contrast to the /3-methyl analogue, which gave a benzothiazep-ine, the difference being due to the electronic influence of the CF3 group (91TL643). 

Sometimes lateral chlorination can occur on a methyl or alkylthio substituent, especially when phosphorus pentachloride or its mixtures with phosphoryl chloride are used (91JHC1549). Reactions of 2-methyl-4(I//)-quinoline (67) exemplify this behavior (81CPB1069) (Scheme 31) 2-chloro-3- and -4-methyquinolines are also subject to methyl chlorinations by similar reagents (91JHC1549). Sulfuryl chloride and NCS are also likely to induce a proportion of lateral chlorination (83KFZ1055 86S835). 

Lateral bromination was observed in the reaction of NBS with 5-chloro-8-methyl- and some related methyl- and alkylthio-quinolines [83KFZ1055 86S835]. 

US patent 6,734,308, Crystal forms of 6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-4-(3-ethynyl-phenyl)-l-methyl-lH-quinolin-2-one, 2,3,-dihydroxy-butanedioate salts and method of production [108]. The invention relates to crystal forms of 6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-meth-yl]-4-(3-ethynyl-phenyl)-1 -methyl-lH-quinolin-2-one, 2,3-dihydroxy butanedioate salts, and to pharmaceutical compositions containing the above compound, methods of treating hyperproliferative diseases, such as cancers, in mammals, especially humans by administering the above compound, and to methods of preparing the crystal forms of the above compound and related compounds. 

It was later claimed that the thermal cyclization of bis(aminomethylene-malonates) (601, R = H, Me, Cl, N02, R1 = Et) by heating in refluxing diphenyl ether for 15-30 min under nitrogen afforded 8-(substituted amino)quinoline-3-carboxylates (603) in 31-75% yields (78USP4123536). In the cases of the methyl and chloro derivatives (601, R = Me, Cl, R1 = Et), l,10-phenanthroline-3,8-dicarboxylates (602, R = Me, Cl, R1 = Et) could also be isolated as byproducts in 3-4% yields. 

The isomeric 1,3-dioxino[4,5-/i]quinoline (698) and l,3-dioxino[5,4-/i]quinoline (700, R = Me) were prepared by cyclization of the appropriate N-( 1,3-benzodioxanyl)aminomethylenemalonates (697 and 699, R = Me) in boiling phosphoryl chloride for 12 hr (72MI5). While the methyl derivative of compound 699 (R = Me) readily gave l,3-dioxino[5,4-/i]quinoline (700, R = Me), the unsubstituted and chloro derivatives (699, R = H, Cl) could not be cyclized by heating in phosphorus chloride, even if triethylamine, SnCl4, or PC15 was also present (72MI5). 

Under acidic conditions, the formation of a nearly 1 1 mixture of 5- and 7-substituted quinoline-3-carboxylates, with a slight excess of the former, was observed from the 3-chloro- and 3-methyl derivatives. The cycliza-tions of 3-nitro, 3-trifluoromethyl, and methoxy derivatives were carried out only in polyphosphate to give mainly the 7-substituted isomers. 

The trichloromethyl group in 4-chIoro-8-methyl-2-(trichloromethyl)quinoline is completely fluorinated with antimony(V) fluoride/antimony(V) chloride when the reaction is carried out in dichloromethane at — 5 to 0 C and then at room temperature for 48 hours to give 4-chloro-8-methyI-2-(trifluoromethyI)quinoIine in 68% yield.4,3... 

Recovery experiments were conducted with the following standards, which were used as received without further purification 5-chlorouracil (Calbiochem), furfural (Aldrich), crotonaldehyde (Aldrich), caffeine (Aldrich), isophorone (Aldrich), 2,4-dichlorophenol (Aldrich), anthraquinone (Aldrich), biphenyl (Ultra Scientific), 2,4 -dichlorobiphenyl (Ultra Scientific), 2,6-bis(l,l-dimethylethyl)-4-methylphenol (Aldrich), 2,2, 5,5 -tetrachlorobiphenyl (Ultra Scientific), benzo[e]pyrene (Aldrich), bis(2-ethylhexyl) phthalate (Scientific Polymer Products), 4-methyl-2-pentanone (Aldrich), quinoline (Kodak), 1-chloro-dodecane (Eastman), stearic acid (Kodak), quinaldic acid (Aldrich), trimesic acid (Aldrich), glucose (Aldrich), glycine (Aldrich), and chloroform (Burdick and Jackson). 

The amino groups of isomeric 5-aminomethyl-8-chloro-6-phenyl-3-methyl-l-oxo-1/7- and -l-methyl-3-oxo-3//-pyrimido[l,2-a]quinolines were acylated with acetic anhydride at room temperature for 1 h (79CPB2927). 5,8,9-Trihydroxy-2,3-dihydro-l//-pyrimido[l,2-a]quinoline-l-carboxylic acid was acylated with acetic anhydride in pyridine at room temperature for 24 h (87T2261). 

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