• 专利附录
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    • 专利摘要:
    3,4-Dihydro-quinazoline derivatives, such as 6-carboxy-2-(2'-ethoxy-phenyl)-3,4-dihydro-4-oxo-quinazoline, are disclosed. The compounds possess anti-allergy properties and can be used for the treatment of allergic conditions.
    公开号:SU786894A3
    申请号:SU762426155
    申请日:1976-12-03
    公开日:1980-12-07
    发明作者:Дориа Джанфедерико；Ромео Чирьяко；Джиральди Пьерникола；Лауриа Франческо；Луиза Корно Мариа；Сберце Пьеро；Тиболла Марчелло
    申请人:Фармиталия Карло-Эрба С.П.А. (Фирма)；
    IPC主号:
    专利说明:

    (54) METHOD FOR PRODUCING DERIVATIVES
    3,4-DIHYDROCHINAZOLINE OR THEIR SALTS
    de or a mixture of water with an organic solvent, followed by isolation of the target product in the form of an acid or its ester, or its salt.
    Dioxane is preferably used as the organic solvent.
    The compounds of the formula I form salts with both inorganic bases such as sodium, potassium, calcium and aluminum hydroxides, and with organic ones, such as lysine, triethylamine, procaine, dibenzylamine, N-benzyl-p-phenethylamine, N, N- dibenzylethylenediamine, N-ethylpiperidine and other organic amines, as well as with acids, for example with inorganic such as hydrochloric, hydrobromic and sulfuric, as well as with organic, such as citric sulfate, and metasulfone.
    Example 1. South of 4-aminoisophthalic acid dimethyl ester in 10 ml of dioxane and 20 ml of anhydrous pyridine is mixed with 20 g of 2-isopropoxybenzoyl chloride at room temperature overnight.
    After dilution with water, the precipitate is filtered off, dissolved in ethyl acetate and washed with 5% sodium bicarbonate solution and then with water. After evaporation in vacuo, the residue is crystallized from isopropyl ether to obtain 4- (2-isopropoxybenzoylamino) -isophthalic acid dimethyl ester (12.3 g, mp. 107-110 ° C), which is dissolved in 80 ml of dioxane and processed 80 ml 1 n. sodium hydroxide solution at room temperature overnight. After acidification with dilute hydrochloric acid, the precipitate is filtered and washed with water until the washings are neutral. 10.9 g of 4- {2-isopropoxybenzoylamino) -isophthalic acid are obtained, which is then treated with 60 ml of acetic anhydride at 90-100s for 15 minutes. After cooling and diluting with 60 ml of isopropyl ether, the resulting precipitate is filtered. 9 g of b-carboxy-2- (2-isopropoxyphenyl) -4H-3,1-benzoxazin-4-one (m.p. 246-250s) are obtained, which is treated at room temperature with 90 ml of 32% hydroxide solution ammonium, and then 45 ml of 2 n. sodium hydroxide for. 120 min nocine acidification 4 n. The hydrochloric acid precipitate is filtered off and crystallized from ethanol-chloroform.
    6-carboxy-2- (2-isopropoxyphenyl) -3,4-dihydro-4-oxoquinazoline is formed (6.6 g; mp. 316-318 C).
    The following compounds are prepared analogously:
    b-carboxy-2- (2-methoxyphenyl) -3, 4-dihydro-4-oxoquinazoline, mp. 295-f
    6-carboxy-2- (2-ethoxyphenyl) -3, 4-dihyd Lo-4-oxoquinazoline, so pl. 305-308 ° C;
    b-carboxy-2- (2-allyloxyphenyl) -3, 4-dihydro-4-oxoquinazoline, so pl. more than 300 ° C (decomposition);
    6-Carboxy-2-4- (2-ethoxyethoxy-phenyl-3,4-dihydro-4-oxoquinazoline, mp 303-306 ° C;
    b-carboxy-2- (2-propoxyphenyl) -3, 4-dihydro-4-oxoquinazolin, m.p. 285-28bs;
    6-carboxy-2- (2-butoxyphenyl) -3, 4-dihydro-4-oxoquinazoline, m.p. 258-260 ° C;
    6-carboxy-2- 2- 1-methylpropoxy) -phenyl-3, 4-dihydro-4-oxoquinazoline,
    b-carboxy-2- (2-hexyloxyphenyl) -3, 4-dihydro-4-oxoquinazoline, m.p. 198-200 ° C
    b-carboxy-2- (3-methoxyphenyl) -3, 4-dihydro-4-oxoquinazoline, m.p. 300С (decomposed);
    b-carboxy-2- (4-methoxyphenyl) -3, 4-dihydro-4-oxoquinazoline, so pl. 300 C (decomposition);
    b-carboxy-2- 2- (2-methylpropoxy) -phenyl-3,4-dihydro-4-oxoquinazoline, m.p. 299-301 ° C;
    b-carboxy-2- 2 - (2-ethoxyethoxy) -phenyl) -3,4-dihydro-4-oxoquinazoline, mp. 242-244 C;
    b-carboxy-2- (2-methoxy-5-methylphenyl; -3,4-dihydro-4-oxoquinazoline, mp 304-306 ° C;
    b-carboxy-2- (2-methoxy-4-methylphenyl) -3,4-dihydro-4-oxoquinazoline; b-carboxy-2- (2-isopropoxy-5-methylphenyl) -3,4-dihydro-4-oxoquinazoline, so pl. 298-300С;
    b-carboxy-2- (2-isopropoxy-4-methylphenyl) -3,4-dihydro-4-oxoquinazoline;
    b-carboxy-2- (2-butoxy-5-methylphenyl) -3,4-dihydro-4-oxoquinazoline;
    b-carboxy-2- {2-butoxy-4-methylphenyl) -3,4-dihydro-4-oxoquinazoline; b-carboxy-2- {2, 4-dimethoxyphenyl) -3,4-dihydro-4-oxoh nazolin, m.p. 346-349 С;
    b-carboxy-2- (2, 5-dimethoxyphenyl) -3,4-dihydro-4-oxoquinazolium,
    m.p. 280-283 ° C;
    b-carboxy-2- (2, b -dimethoxyphenyl) -3,4-dihydro-4-oxoquinazoline, so pl. 279-281 ° C;
    b-carboxy-2- (2-methoxy-5-fluorophenyl) -3,4-dihydro-4-oxoquinazoline.
    Example 2. 17 g of 4-aminoisophthalic acid are boiled in 800 ml of methanol and 39 ml of boron trifluoride etherate for 18 hours. After concentration in vacuo, the mixture is diluted with water and filtered. The mixture is shaken in a mixture of 250 ml of ethyl acetate and 250 ml of 5% strength sodium bicarbonate solution. The aqueous phase is separated, the precipitate is acidified, filtered,
    washed with water until the washings are neutral. 12 g of 2-amino-5-carbethoxybenecoic acid are obtained, which is then reacted with 60 ml of ethyl chlorocarbonate in BO ml of dioxane for 20 hours at boiling. Next, 48 ml of acetyl chloride is added and the boiling is continued for 12 hours. The reaction mixture is evaporated vacuum, and the concentrate is diluted with ethyl ether and filtered. As a result, 10 i 5-carbomethoxycarboxyanethranilic acid anhydride (mp 275-278 C) is obtained, which is treated with 25 ml of 32% ammonium hydroxide in 25 ml of dimethylformamide at room temperature for 30 minutes. After dilution with water, the precipitate is filtered and washed until the washings are neutral. 8.1 g of 2-amino-5-carboxybenzamide are obtained, which is then dissolved in 80 ml of dioxane and 10 ml of pyridine and stirred until neutral. As a result of crystallization of the precipitate from methanol, 8.5 g of 1- (4-fluorobenzoylamino) -5-carbomethoxybenzamide are obtained. By treating it with a mixture of 40 ml of 2N. sodium hydroxide and 40 ml of dioxane at room temperature for 8 hours, followed by dilution with water and acidification, a precipitate is obtained which is filtered and washed with hot ethanol. The result of 7.1 g of 6-carboxy-2- {4-fluorophenyl) -3,4-dihydro-4-oxoquinazoline, so pl. 397-399 ° C.
    The following compounds are prepared analogously:
    6-carboxy-2- (3-chlorophenyl) -3,4-dihydro-4-oxoquinazoline, m.p. (decomposed) above 300 ° C;
    6-carboxy-2- (2-chlorophenyl) -3,4-dihydro-4-oxoquinazoline;
    b-carboxy-2- (3-chlorophenyl) -3,4-dihydro-4-oxoquinazoline;
    6-carboxy-2- (2-fluorophenyl) -3,4-dihydro-4-oxoquinazoline;
    6-carboxy-2- (2-methylphenyl) -3,4-dihydro-4-oxoquinazoline;
    6-carbxy-2- (3-methylphenyl) -3,4-dihydro-4-oxoquinazoline;
    6-carboxy-2- {4-methylphenyl) -3,4-dihydro-4-oxoquinazoline;
    6-carboxy-2- (4-isopropylphenyl); - 3, 4-digndro-4-oxoquinazoline;
    6-carboxy-2- (4-tert-butylphenyl) -3,4-dihydro-4-oxoquinazoline.
    Example 3. 7g of 6-carboxy-2- (2 -pyrazinyl) -4H-3,1-benzooxazin-4-one, obtained by the method described in Example 1, is treated with 70 ml of 32% ammonium hydroxide and boiled in flow. 24 hours. After cooling and acidification with acetic acid, filter and wash with ethanol. 5.1 g of 6-carboxy-2- {2-pyrazinyl) -3,4-dihydro-4-oxoquinazoline are obtained, m.p. above Srayl.).
    Similarly, the following compounds are prepared:
    6-carboxy-2- {2-pyridyl) -3,4-dihydro-4-oxoquinazoline;
    6-carboxy-2- (3-methoxy-2-pyridyl) -3,4-dihydro-4-oxoquinazoline, 5 m.p. 273-276 0;
    6-carboxy-2- (3-ethoxy-2-pyridyl) -3,4-dihydro-4-oxoquinazoline, m.p. 291-294 C;
    Q is 6-carboxy-2- (3-propoxy-2-pyridyl) -3,4-dihydro-4-oxoquinazoline;
    6-carboxy-2- (3 -isopropoxy-2-pyridyl) -3,4-dihydro-4-oxoquinazoline;
    6-carboxy-2- (3-butoxy-2-pyri5 dil) -3,4-dihydro-4-oxoquinazoline.
    Example 4. Similar to that described in Example 2, using 2-amino-4-carbomethoxybenzamide and 2-alkyl-oxy-5-aminosulfonyl-benzoyl chlorides as the starting material, the following compounds were obtained:
    6-carboxy-2- (2-methoxy-5-aminosulfonylphenyl) -3,4-dihydro-4-oxoquinazoline;
    5 6-carboxy-2- (2-isopropoxy-5-aminosulfonylphenyl) -3 / 4-dihydro-4-oxoquinazoline;
    6-carboxy-2- (2-butoxy-5-aminosulfonylphenyl) -3,4-DIHIDRO-4-OXO, quinazoline;
    6-carboxy-2- (2-butoxy-5-aminosulfonylphenyl) -3, 4-DIHIDRO-4-OXOH quinazoline;
    / t
    6-carboxy-2- (2-methoxy-5 -N-ethylaminosulfonylphenyl) -3,4-dihydro-4-oxoquinazoline;
    6-carboxy-2- (2-isopropoxy-5 -N-ethylaminosulfonylphenyl) -3,4-dihydro-4-oxoquinazoline;
    6-carboxy-2- (2-butoxy-5 -N0-ethylaminosulfonylphenyl) -3,4-dihydro-4-oxoquinazoline;
    6-carboxy-2- (2-methoxy-5 -N-isopropylaminosulfonylphenyl) -3,4-dihydro-4-oxoquinazoline;
    lg 6-carboxy-2- (2-isopropoxy-5-N-isopropylaminosulfonylphenyl) -3,4-dihydro-4-oxoquinazoline;
    b-carboxy-2- (2-butoxy-5 -N-isopropylminosulfo-ylphenyl) -3, 4-di. hydro-4-oxoquinazoline;
    6-car6oxy-2- (2-methoxy-5 -N-tert-butylaminosulfonylphenyl) -3,4-dngidiyu-4-oxoquinazoline, m.p. 291-294c;
    b-carboxy-2- (2-isopropoxy-5 55 -N-tert-butylaminosulfonylphenyl) -3, 4-dihydro-4-oxachinazoline;
    6-carboxy-2- (2-butoxy-5-N-tert-butylaminosulfonylphenyl) -3,4-dihydro-4-oxoxy amino;
    60 6-carboxy-2- (2-methoxy-5 -N-methyl-M-ethylaminosulfonylphenyl) -3,4-dihydro-4-oxoquinazoline;
    6-carboxy-2- (2-methoxy-5 -N-methyl-M-isopropylaminosone phonnylfennl) -. 5 -3,4-dihydro-4-oxoquinazoline; b-darboxn-2- (2-methoxy-5 -methyl-N-tert-butylaminos in eh von ylfenyl) -3,4-dihydro-4-oxoquinazoline; 6-carboxy-2- (2-methoxy-5-N, N-di rytylaminosulfonylphenyl) -3,4-dihydro-4-oxoquinazoline. Example 5. 7.5 g of 6-carboxy-2- (2-isopropoxyphenyl) -3,4-dihydro-4-oxoquinazoline, prepared as described in example 1, is treated with an excess (2 mol / mol) of thionyl chloride in dioxane at boiling for 4 hours. After cooling and concentration in vacuo, the dry residue is treated with excess absolute ethanol at a temperature for 2 hours. After cooling, the precipitate is filtered and washed with ethanol and water. 6.3 g of 6-carboxy-2- (2-isopropoxyphenyl) -3,4-dihydro-4-oxoquinazoline are obtained. The following compounds are prepared in a similar manner: 6-carbethoxy-2- (2-methoxyphenyl) -3, 4-dihydro-4-oxoquinaeolin; 6-carbethoxy-2- (2-ethoxyethoxyphenyl) -3,4-dihydro-4-oxoquinazoline; 6-carbethoxy-2- (2-butoxyphenyl) -3, 4-DIHIDRO-4-oxoquinazoline; b-carbethoxy-2- (2-methoxy-5-methylphenyl) -3,4-dihydro-4-oxoquinazoline; , b-carbethoxy-2- (2-methoxy-5 -N-isopropylaminosulfonylphenyl) -3,4-dihydro-4-oxoquinazoline; b carbethoxy-2- (2-methoxy-5 -W-tert., butyl-1 minosulfonylphenyl) -3, 4-dihydro-4-oxoquinazoline; b-carbethoxy-2- (3-methoxy-2-pyridyl) -3,4-dihydro-4-oxoquinazoline. Example b. 23g of 6-carboxy-2- - (2-methylpropoxy) -phenyl-3, 4-digdro-4-oxoquinazoline, prepared as described in example 1, is suspended in 200 ml of dioxane and boiled after adding 12 ml of thionyl chloride for b h. After cooling, the reaction mixture is treated at room temperature with vigorous stirring and external cooling with a slow flow of dry ammonia for 2 hours. The precipitate is filtered off and washed with water until neutral wash water. 22.2 g of 6-carboxamido-2-2- (2-methylpryupoxyphenyl) D-3 /, 4-dihydro-4-oxoquinazoline are obtained, which are treated with 37.5 g of toluenesulfonyl chloride and 33 ml of pyridine in 160 ml of dimethylformamide at EO- C for 5 hours. After cooling and diluting with 1.5 l of water, the mixture is filtered, the precipitate is washed until neutral. After washing with warm isopropyl ether, 15.9 g of b-cyano-2- 2- (2-methylpropoxy) -phenyl-3,4-dihydro-4-oxoquinazoline is obtained, which is treated with 16.8 g of sodium azide and 13.8 g of chloro ammonium nitride in 150 ml of dimethyl forms and for 3 hours. After cooling, diluting with water and acidifying to pH 4 with hydrochloric acid, the precipitated precipitate is washed with water and crystallized from ethanol. The result is 11.9 g of b- (5-tetrazolyl) - (2-methylpropoxyphenium) -3, 4-dihydro-4-oxoquinazoline, m.p. (decomposed) 280 ° C. The following compounds are prepared analogously: 6-15-tetrazolyl) -2- (2-methoxyphenyl) -3,4-dihydrr-4-oxoquinazoline; b- (5-tetrazolyl) -2 (2-methoxy-5-methylphenyl), 4-dihydro-4-oxrhinazoline; b- (5-tetrazolyl) -2- (2-isopropoxyphenyl) -3,4-dihydro-4-6 xoquinazoline; 6- (5-tetrazolyl) -2- (2-butoxyphenyl) -3,4-dihydro-4-oxoquinazoline; 6- (5-tetrazolyl-2-) 3-methoxy-2-pyridyl) -3,4-dihydro-4-oxoquinazoline; b- (5-tetrazolyl) -2- (3-butoxy-2-pyridyl) -3, 4-dihydro-4-oxoquinazolin. Example 7. 3.5 g of b-carboxy-2- (2-isopropoxyphenyl) -3,4-dihydro-4-oxoquinazoline is treated with a hot aqueous solution of 800 mg of sodium bicarbonate. After cooling and filtration, the solution is evaporated to a minimum volume and diluted with 4 vol. acetone. 3.2 g of sodium salt of 6-carboxy-2- (2-isopropoxyphenyl) -3,4-dihydr6-4oxoquinazoline are obtained. Similarly, sodium salts are prepared: b-carboxy-2- (2-methoxyphenyl) -3, 4-dihydro-4-oxoquinazoline; b-carboxy-2- (2-methoxy-5-methylphenyl) -3,4-DIGIDRO-4-oxoquinazoline; b-carboxy-2- (3-methoxy-2-pyridyl) -3,4-dihydro-4-oxoquinazoline; b-carboxy-2- (3-ethoxy-2-pyridyl) -3,4-dihydro-4-oxoquinazoline; b-carboxy-2- (3-butoxy-2-pyridyl) -3, 4-dihydro-4-oxoquinazoline. Example 8. 7g b-chlorocarbonyl-2- (2-isopropoxyphenyl) .- 3,4-dihydro-4-oxoquinazoline, prepared as described in example 6, is treated with a solution of 2 g of 5-aminotetrazole in 70 ml of dioxane in the presence of 2, 7 g of sodium bicarbonate at room temperature for 6 hours. The precipitate is filtered off, washed with water and then dimethylformamide-ethanol is crystallized from the mixture. The result is 4.8 g of 6- (5-tetrazolylamino) -2- (2-isopropoxyphenyl) -3,4-dihydro-4-oxoquinazoline. The following compounds are prepared analogously: b- (5-tetrazolyl-amido) -2- (2-methoxyphenyl) -3,4-dihydro-4-oxoquinazoline;
    b. (5-tetrazolyl amido) -2- (2-butoxyphenyl) -3,4-dihydro-4-oxoquine zoline;
    (6- (5-tetrazolyl-amido) -2- (2-methoxy-3-methylphenyl) -3,4-dihydro-4-oxoquinazoline;
    6- (5-tetrazolyl-amido) -2- (3-methoxy-2-pyridyl) -3,4-DIHIDRO-4-OXO-quinazoline.
    Example 9. 5.6 g of sodium salt of b-carboxy-2- (2-isopropoxyphenyl) -3,4-dihydro-4-oxoquinazoline, prepared as described in example 7, is suspended in 50 ml of dimethylformamide and treated with 5 ml of chloromethyl pivalate in the presence of 2 4L of triethylamine at 60 ° C for 16 hours. After cooling and diluting with water, extract with ethyl acetate. The organic phase is then washed with a 5% sodium bicarbonate solution and evaporated to dryness in water. The residue is crystallized from ether. 5.2 g of 6-carboxy-2- (2-isopropoxyphenyl) -3, 4-dihydro-4-hydroxy-quinazoline pivaloyloxymethyl ester are obtained.
    The following compounds are prepared analogously:
    6-carboxy-2- (2-methoxyphenyl) -3, -dihydro-4-oxoquinazoline;
    6-carboxy-2- (2-ethoxyphenyl) -3,4-dihydro-4-oxoquinazoline;
    6-carboxy-2- (2-butoxy-2-phenyl) -3,4-digidro-4-oxoquinazoline;
    6-carboxy-2- (z-methoxy-2-pyridyl) -3, 4-dihydro-4-oxoquinazoline.

    Example 10. Using the procedure outlined in example 5 and the corresponding aliphatic alcohols, the following 6-carboxy-2- (2-methoxyphenyl) -3,4-dihydro-4-oxoquinazoline esters are obtained: isopropyl, tributyl, octyl and undecyl.
    Example 11. b, 1g of 6-chlorocarbonyl-2- (2-isopropoxyphenyl) -3,4-dihydro-4-oxoquinaeoline, prepared according to the procedure described in example 5, is suspended in 60 ml of dioxane and 4 are added to the suspension , 2 ml of diethylaminoethanol and 1 m of triethylamine and stirred at room temperature for 18 h.
    After dilution with water, the precipitate is filtered, washed until neutral and crystallized from methanol. 5.3 g of diethylaminoethyl ester of 6-carboxy-2- (2-isopropoxyphenyl) -3, 4-DIGIDRO-4-OXO1-quinazoline are obtained.
    Analogously, get diethylaminoethyl esters
    6-carboxy-2- (2-methoxyphenyl) -3, 4-dihydro-4-oxoquinazoline;
    6-carboxy-2- (2-ethoxyphenyl) -3, 4-dihydro-4-oxoquinazoline;
    6-carboxy-2- (2-butoxyphenyl) -3 „4-dihydro-4-oxohiyazolin a;
    b-carboxy-2- 2 - {2-ethoxyethoxy) -phenyl-3, 4-dihydro-4-oxoquinazoline;
    6-carboxy-2- (3-methoxy-2-pyridyl) -3,4-dihydro-4-oxohiyazolin.
    , g Example 12. Using the procedure described in example 11 and using either dimethylaminoethanol or 2- (pyrrolidyl-1) -ethanol or morpholinoethanol Q NOL as reagents, the esters are obtained:
    6-carboxy-2- (2-isopropoxyphenyl) -3,4-dihydro-4-oxoquinazoline; 6-carboxy-2- (2-butoxyphenyl) -3, 4-dihydro-4-oxoquinazoline;
    6-carboxy-2- 2- (2-ethoxyethoxy 1 5 -phenyl-3,4-dihydro-4-oxoquinazoline; 6-carboxy-2- (2-methoxy-3-methyl phenyl) -3,4-dihydro- 4-rxoquinazoline; 6-carboxy-2- (3-methoxy-2-pyridyl) -3,4-dihydro-4-oxoquinazoline; 20 6-carboxy-2- (2-methoxy-2-pyridyl) -3.4 -dihydro-4-oxoquinazoline.
    Example 13. 9g of dimethyl 4-aminoisophthalic acid in
    25 60 ml of dioxane and 18 ml of pyridine are mixed with 3.8 g of hexanoyl chloride. At room temperature for 16 hours. After diluting with water and extracting with ethyl acetate, the extract is washed
    Q 40% citric acid solution and 3% sodium bicarbonate solution and evaporate to dryness. 14.8 g of dimethyl 4-hexanoyl-aminoiso-isoic acid are obtained, which are then dissolved in 73 ml of dioxane and stirred with 73 ml of 2 and. solution units whom soda at room temperature for 6 .h. After acidification with hydrochloric acid, the precipitate is filtered and washed until neutral. 11.4 g of 4-hexanoylamino-isophthalic acid are obtained, and the mixture is boiled in 26 ml of acetic anhydride for 10 minutes. After cooling, diluting with 30 ml of isopropyl ether
    J and 6-carboxy-2-pentyl-4H-3, 1-benzoxazin-4-one (7.3 g; m.p. 183-190s) are obtained by filtration, which is stirred at room temperature first with 70 ml of 32% - hydroxide ammonium for 16 h, and then with 30 ml of 3 K. sodium hydroxide solution for 2 h. After acidification. 2 n. Hydrochloric acid the precipitate is filtered and crystallized from ethanol. Get 6,1 g of 6-carboxy-2-pentyl55-3,4-dkgidro-4-oxoquinazoline, so pl. 311-313 p.
    The following compounds are prepared analogously:
    0 6-carboxy-2-propyl-3,4-dihydro-4-oxoquinazoline;
    6-carboxy-2-isopropyl-3,4-dihydro-4-oxoquinazoline, m.p. 284-285 ° C;
    6-carboxy-2- (2-methylpropyl) 5 -3,4-diHydro-4-oxoquinazoline;
    权利要求:
    Claims (3)
    [1]
    1. The method of obtaining derivatives
    3,4-dihydroquinazoline of the general formula where R is a carboxy or carbalkoxy group, where is alkyl with 1-12 carbon atoms, carbodiethylaminoethoxy, carbodimethylaminoethoxy, carb- £ 2 (pyrrolidinyl-1)] ethoxy, carb p- ( morpholinyl-1)] ethoxy group, 5-tetrazolyl group or COR ^ group, where R ^ -NHOH or NR ^ R ^ H where .Cd and R $ are independently hydrogen or alkyl with 1-10 carbon atoms or, when the poison is hydrogen, then. R y may also be 5-tetrazolyl or a group CHRgCOOH, where Rg is alkyl with 1-6 carbon atoms or hydrogen;
    R, [- alkyl with 2-20 carbon atoms, possibly substituted by an oxy, methoxy or ethoxy group, alkenyl with 2-3 carbon atoms, phenyl containing 1-3 substituents from the number of halogen, alkyl with 1-6 carbon atoms, alkoxyl with 1-5 carbon atoms, aminosulfonyl, alkylLamino- or dialkylaminosulfonyl, where alkyl with 1-4 carbon atoms, allyloxy group, unsubstituted pyridyl or substituted with alkoxyl with 1-6 carbon atoms, pyrrolidinyl or pyrazinyl, or their salts, distinguishing with the fact that the compound of general formula 35 is cyclized at a temperature from room temperature to 300 ° С in water or a mixture of water with an organic solvent, followed by isolation of the target product in the form of an acid or its ester, or its salt.
    [2]
    2. A method of obtaining derivatives.
    [3]
    3,4-dihydroquinazoline according to π. 1, about the fact that in ka. dioxane is used as the organic solvent.
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    公开号 | 公开日
    DK546776A|1977-06-06|
    NO146095B|1982-04-19|
    FI763391A|1977-06-06|
    AU505660B2|1979-11-29|
    FR2333511B1|1979-03-02|
    GB1523081A|1978-08-31|
    DK147855C|1985-06-10|
    HU177817B|1981-12-28|
    NO146095C|1982-08-11|
    NO764135L|1977-06-07|
    IL50849D0|1977-01-31|
    IT1050750B|1981-03-20|
    ATA894376A|1979-07-15|
    CA1084051A|1980-08-19|
    AU1947276A|1978-05-18|
    AT355029B|1980-02-11|
    US4251531A|1981-02-17|
    FR2333511A1|1977-07-01|
    NZ182778A|1978-07-28|
    JPS5543464B2|1980-11-06|
    NL7613450A|1977-06-07|
    FI64359C|1983-11-10|
    ZA766745B|1977-10-26|
    BE848696A|1977-03-16|
    CH626075A5|1981-10-30|
    CH626073A5|1981-10-30|
    DE2654215A1|1977-06-16|
    FI64359B|1983-07-29|
    DK147855B|1984-12-24|
    IL50849A|1980-11-30|
    JPS5271485A|1977-06-14|
    SE7613588L|1977-06-06|
    CS194786B2|1979-12-31|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US3696102A|1970-03-09|1972-10-03|Pfizer & Co C|Process for the synthesis of substituted quinazolin-4-ones|ES524262A0|1982-08-05|1984-11-16|Erba Farmitalia|"PROCEDURE FOR PREPARING QUINAZOLINE DERIVATIVES"|
    JPS6216899Y2|1982-08-10|1987-04-28|
    US4666913A|1985-11-22|1987-05-19|William H. Rorer, Inc.|Hydroxy and aminothiazolyl-benzodiazinone compounds, cardiotonic compositions including the same, and their uses|
    GB8827988D0|1988-11-30|1989-01-05|Smith Kline French Lab|Chemical compounds|
    US5430148A|1992-03-31|1995-07-04|Agouron Pharmaceuticals, Inc.|Antiproliferative quinazolines|
    US6632961B1|1998-05-22|2003-10-14|Abbott Laboratories|Antiangiogenic drug to treat cancer, arthritis and retinopathy|
    EP1080070B1|1998-05-22|2006-11-22|Abbott Laboratories|Antiangiogenic drug to treat cancer, arthritis and retinopathy|
    CO5170498A1|1999-05-28|2002-06-27|Abbott Lab|BIARIL SULFONAMIDS ARE USEFUL AS CELL PROLIFERATION INHIBITORS|
    EP1389103A4|2001-04-23|2005-09-14|Univ Virginia|Synthesis and evaluation of novel phthalimide mimics as anti-angiogenic agents|
    US7872052B2|2003-06-06|2011-01-18|Arexis Ab|Use of heterocyclic compounds as SCCE inhibitors|
    CN100518740C|2003-06-06|2009-07-29|阿里克斯股份公司|Use of heterocyclic compounds as SCCE inhibitors|
    JP5193866B2|2006-08-08|2013-05-08|あすか製薬株式会社|Quinazoline derivatives|
    DK2118074T3|2007-02-01|2014-03-10|Resverlogix Corp|Compounds for the prevention and treatment of cardiovascular diseases|
    EP2408454A2|2009-03-18|2012-01-25|Resverlogix Corp.|Novel anti-inflammatory agents|
    EP2421533B1|2009-04-22|2018-10-17|Resverlogix Corp.|Novel anti-inflammatory agents|
    US10111885B2|2015-03-13|2018-10-30|Resverlogix Corp.|Compositions and therapeutic methods for the treatment of complement-associated diseases|
    GB201510254D0|2015-06-12|2015-07-29|Syngenta Participations Ag|Improvements in or relating to organic compounds|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    IT29998/75A|IT1050750B|1975-12-05|1975-12-05|DERIVATIVES OF 3.4 OF HYDRO CHINAZOLINE|
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