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    • 专利摘要:
    The invention relates to a composite insect attractant for male white-line dart moths [Scotia segetum] containing 7[Z]-dodecen-l-ol acetate of the formula [I] <IMAGE> (I) and 9[Z]-tetradecen-l-ol acetate of the formula [II] <IMAGE> (II) as active agents in a weight ratio of I to II of [50-99]:[50-1], optionally along with a liquid or solid adjuvant. Another object of the invention is an insect trap containing said composition and a process for attracting and trapping male white-line dart moths as well as a process for disrupting their mating by air permeation technique. The invention relates further to a novel process for the preparation of the active ingredients of the composition.
    公开号:SU999973A3
    申请号:SU782893651
    申请日:1978-12-28
    公开日:1983-02-23
    发明作者:Хермец Иштван；Месарош Золтан；Брайнинг Тибор；Вираг Шандор；Вашвари Лелле；Хорват Агнеш；Надь Габор；Манди Аттила；Сюч Тамаш；Биттер Иштван；Шебештьен Дьюла
    申请人:Хиноин Дьедьсер Еш Ведьесети Термекек Дьяра Рт (Инопредприятие)；
    IPC主号:
    专利说明:

    group -NsCRgR. where R is hydrogen or lower alkyl, R — y is lower alkyl, phenyl, or di (lower) alkylamino-phenyl,
    or their pharmaceutically acceptable salts, or their optically active isomers.
    The method is that the compound of the formula
    (P)
    or its tautomeric forms, or optically active isomers,
    where dotted lines are possible
    additional communication;
    R. -Rj are as indicated;
    L is halogen, hydroxyl, or
    p-toluensulfonyloxyamine group,
    subjected to interaction with the compound of the General formula
    Mules III are usually carried out in the presence of acid binding substances, which are preferably alkali metal carbonates (potassium or sodium carbonate),
    alkali metal bicarbonates (e.g. potassium or sodium bicarbonate), salts of weak organic acids with alkali metals (e.g. sodium acetate) or excess
    starting compound of formula 111. The reaction can be carried out in an inert solvent. Aromatic hydrocarbons, for example benzene, toluene, xylene, or ether, for example ethyl acetate, alcohols, for example methanol or ethanol or dimethylformamide are used as the reaction medium. 0-200 ° C, preferably at room temperature, but can also be carried out at heating or at the boiling point of the reaction mixture,
    As an intermediate in the reaction, there appears to be a compound of the general formula
    HjN-NC
    op;
    where R and Ry have the indicated values. The desired product is isolated or washed by the resulting ester, or the resulting acid is subjected to a subsequent transformation into the corresponding 111th ester, amide or hydrazide, or the subsequent benzoylation of the resulting x: compound of the formula I, where R is hydrogen, or the subsequent reaction of the obtained compound of the formula I, where IL and Rg are hydrogen atoms, with a compound of the general formula O C RgR7 where R .. and R have the indicated values.
    The desired products are isolated in free form or in the form of pharmaceutically acceptable salts (physiologically tolerable salts, hydrates, stereoisomers, optically active and spatial isomers and tauto, measures of compounds of general formula I). . Lower alkyls as well as lower alkoxy are normal or branched aliphatic, saturated hydrocarbon groups with 1-6, preferably with 1-4 carbon atoms, for example methyl, ethyl, i-propyl, isopropyl, n-butyl, secondary butyl, tertiary butyl , n-pentyl, neopentyl, n-hexyl, etc. The lower alkanoyl group is an acidic residue of alkanecarboxylic acids with 1-6, preferably 1-4 carbon atoms, for example, formyl, acetyl, propionyl, butyryl group.
    The interaction of the compound with formula 2 with the compound form .7,
    where R bond indicated by the dotted line, have the indicated meanings contained in the reaction mixture, which when exposed to
    air oxygen at room temperature or heating, c. which results in oxidation, is converted to a compound of formula I. If the starting material is used
    General formula II, in which L is hydroxyl, it is advisable to carry out the reaction in the presence of a water-binding substance, for example dicyclohexylcarbodiimide.
    Compounds of general formula I can be isolated from the reaction mixture in a known manner. In many cases, the compound. General formula I is precipitated from the reaction mixture in the form of its salts or hydrate, which can
    separate by filtration or centrifugation. If the reaction is carried out by introductory medium, the final product is extracted from the reaction mixture with a suitable organic solvent, e.g. 6eH3onoMj chloroform, ether, and the organic extract is evaporated. If the reaction is carried out in an organic solvent medium, the compound
    the general formula I is isolated by removal of the solvent. The resulting Compounds of general formula I can be purified by recrystallization or by chromatography. The obtained compound of the general formula I can be converted, if desired, into another compound of the general formula, produced in the R groups and / or which are carried out in a known manner under the usual conditions for this type of reaction. A carboxyl group standing as a substituent R or R can be etherified in a known manner to an alkoxycarbonyl-arylox carbonyl or aralkyloxycarbonyl group. Esterification may occur, for example, due to being converted with an appropriate alcohol or phenol in the presence of an acidic catalyst or by treatment with a diazoalkane, for example, diazomethane, diazoethane. The carboxyl of the corresponding derivative can be decarboxylated by heating it, and a corresponding derivative arises containing hydrogen on the site of the carboxyl group. Decarboxylation is expediently carried out in the presence of an acid, for example, phosphoric. The derivative containing the carboxyl group can be reacted with the corresponding amine to the acid amide, which is substituted in this case. Substituted acid amides are obtained in a known manner via an active ester, for example, an active ester formed with ethyl chloroformate. . The ether group contained as a substituent Rj or R, respectively, can be subjected to mutual action by heating with an excess of the corresponding alcohol. The ester of the general formula I can be converted by acidic or alkaline treatment to the corresponding carboxylic acid of general formula I. The alkaline hydrolysis is carried out by heating with an alkali metal hydroxide in an aqueous or alcoholic medium, and the acid is liberated from the alkali metal salt due to acidification. During the hydrolysis with mineral acids, the free carboxylic acid is obtained directly. The ester of general formula I, by reaction with ammonia in an aqueous-alcoholic medium, can be converted to the corresponding acid amide of formula I by treatment with hydrazine, in the necessary case, with a hydrated (hydrizine, methyl or phenylhydrazine) to the corresponding hydra of general formula I. Compound of general formula 1 containing hydrogen as R, can be converted by benzophase into the corresponding compounds of general formula I containing a benzoyl group as a substitute for R. The acylation is carried out in a manner already known by the corresponding acid or its reactive derivatives. A compound of general formula I containing hydrogen as Yad-and R can be condensed with an aldehyde into the corresponding compound of general formula 1 containing a group of the general formula instead. The condensation reaction is carried out in an inert solvent (for example benzene, toluene) with heating or ktsliatnoy temperature. The water resulting from the reaction can be removed using the azeotropic distilled method. or water binding agents. As the aldehyde, for example, acetaldehyde or benzaldehyde can be used. Of the compounds of general formula 1, salts can be formed with physiologically tolerable acids, for example, hydrochlorides, hydrobromides, hydroiodides, sulfates, nitrates, phosphates, maleates, succinates, acetates, tartrates, lac-tates, fumarates, citrates, etc. Among the compounds of general formula I containing carboxyl or sulphonic acid, salts can be formed with physiologically tolerated bases, for example alkali metal salts such as sodium and potassium salts, as well as salts formed with organic allyns such as; as salts of triethylamine, ethanolamine, etc. The compounds of general formula I can be isolated from the salts formed with acids or alkalis in a known manner. From the basic compounds of the general formula I, it is possible, by reacting with inorganic or organic acids, to form additive compounds. Salt formation is carried out in a known manner by introducing an orot-appropriate compound of general formula I together with the acid used in equivalent volume or in excess to an inert organic solvent. Compounds of general formula I containing acidic groups (carboxyl or sulphonic acid) can be reacted with a base (e.g. alkali metal, alkaline earth metal hydroxide, organic amines) in the salt formed with a base, Those compounds of general formula 1 which contain as R substituents from hydrogen, a center of asymmetry, and can exist as optically active compounds or as a racemate. Optically active compounds of general formula I can, for example, be obtained using optically active starting materials or separating the racemate compound of general formula I into its optically active antipodes. This can be done by a known method. Compounds of general formula 1 containing carboxyl groups can, for example, be divided into optical isomers, subjecting the racemate to an optically active base, for example, threo 1- (p-nitrophenyl) -2-aminopropane 1, 3-diol. The members of the resulting pair of diastereoisometric salts are separated from each other on the basis of their different physical properties, and the optical antipodes of general formula 1 separated from each other are released from the salt by treatment with a strong base. Compounds of general formula I exhibit many pharmacological effects: they are anti-inflammatory, analgesic, anti-atherosclerotic, reduce blood clot aggregation, regulate the circulatory system and heart function, act on the central nervous system, have tranquilizing, p; c / antagonistic, antibacterial, and antibacterial factors; , as well as anti-ulcer action. Therefore, the compounds of general formula I are applicable in veterinary medicine and medicine. Their action against allergy and asthma is especially valuable Allergic reactions resulting from the interaction of antigens and antibodies occur in various organs and tissues. As a remedy for asthma, disodium chromoglycate (1.3-1 bis- {2 carboxychromon-b-yl-oxy) -2-hydroxypro pan, Intal R) is common, which is not taken orally, but is used only in the form of inhalations aids. Compounds of general formula I, either orally or intravenously or in the form of inhalations, give positive results in the treatment of allergic symptoms. The efficacy of the compounds of Formula 1 has been proven using standard tests to determine the antiallergic effect. Tests were performed on rats. The results are shown in the table. The use of 1 A-test, / JM / kg, when administered intravenously, gave the following re 3 ultates: 9 (2-Carboxyphenyl} -hydrazonou-b-methyl-4-oxo-6, 7,8,9 -tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid 0.48 9-G (4-Ethoxyphenyl) -hydrazono-b-methyl-4-OXO-6, 7,8,9-tetrahydro- 4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid 1,0 9-p4-Chlorophenyl) -hydrazno-6-methyl-4-OXO-6, 7,8,9-tetrahydro-4H-pyrido (1, 2-a) pyrimidine- 3-carboxylic acid 0.53 9- (3-Pyridylhydrazono) -b-methyl-4-oxo-6, 7, 8,9-tetrahydro-4H-pyrido (1,2- a) pyrimidine-3-carboxylic acid 0.54 From It can be seen that the compounds of formula I are also effective for oral use. When administered intravenously, the compounds of the formula D are also more effective than the known control compounds. The toxicity of the proposed compounds is insignificant, determined in rats and mice, and with l-Dr-Q 500 mg / kg orally. The compounds of general formula I can be used in pharmacy in the form of preparations containing the active substance, as well as solid or liquid, inorganic or organic synthetic carriers. The preparations are made in the usual manner in the manufacture of drugs. The content of active substance in the preparation can vary widely and lies in the range of 0.00590%. The daily dose in terms of the active substance can vary widely and depends on the age, weight and condition of the patient, as well as on the dosage form of the preparation and the activity of the active active substance. For oral administration, the daily dose is 0.015–15 mg / kg, while, for intravenous administration and inhalation, the daily dose, divided into several partial doses, is in the range of 0.001–5 mg / kg. These data are indicative; in individual cases and depending on the physician's instructions, the dose may be increased or decreased in dose. Example 1 6.3 g (0.02 mol) of ethyl 9-bromo-6-methyl-4- (1 x Co-6, 7,8,9-tetrahydro-4H-pyrido {, 2-a) pyrimldin-3-carboxylic acid is dissolved in т t in 30 ml of ethanol, and 4, 3 t-ui (0.044 mol) phenylhydrazine is added to the solution. After boiling for 4 hours, the solvent is distilled off under reduced pressure. 30 ml of water and 15 ml of chloroform are added to the residue, and then with stirring, the pH of the aqueous phase is set to 2-3 by addition of a 10% aqueous solution of hydrochloric acid. The organic phase is separated, the aqueous phase is extracted twice with 15 ml of chloroform. The purified organic phases are dried over calcined sodium sulphate, the solvent is distilled off under reduced pressure. A red oil remains, which is crystallized from two, threefold amount of ethanol. 5.3 g (68.6%) of the product are obtained, melting at 86-81 ° C. The compound is crystallized with 1 mol of ethanol. The ethanol is removed by drying at 9Q-iQO ° C in a vacuum over phosphoric anhydride. Dried 9- (phenylhydrazono) -6-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid ethyl ester melts at 138-139 s , P p and Me p 2. 2.5 g (0.01 mol of 9-hydroxy-6-methyl-4-ca-6,7-dihydro-4H-pyrido (1,2-a) pyrimidine ethyl ester 3-carboxylic acid is dissolved in 7.5 ml of anhydrous ethanol, 1.2 ml (0.12 mol) of phenyl-1-hydrazine is added to the solution. After the half-hour boiling, the reaction mixture can be cooled. Orange crystals are precipitated. (90.6%), mp. 86-87 C. The compound is crystallized with 1 mol of ethanol, which can be removed from with an ear at 90-100 ° C in vacuum over phosphoric anhydride. Dried ethyl ester of 9- (phenylhydrazono) -6-methYL-4-OXO-6, 7,8-tetrahydro-4H-pyri to (1,2-a) pyrimidine-3-carboxylic acid melts at 133-139 ° C and does not have a difference in the melting point of the product obtained in Example 1. The following compounds are prepared in a similar way. Ethyl ester-b-methyl-9- (m-methyl phenyl hydra, ) -4-oxo-6,7,8,9-tetrahydrs5-4H-pyrido (1, 2-a) pyrimidine-3-carboxylic acid, mp, 159leO Co 9- (i-chlorophenylhydrazono) ethyl ester -methyl-4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimid n-3-carboxylic acid, m.p. 177178 ° C, 6-methyl-9- (and-methyl-phenylhydrazono) -4-oxo-6,7,8, 9-tetrahydro-4H-pyrido ethyl (1,2-a) pyrimide 1 n-3-carboxylic acid m.p. 147149 C. 9- (2,6-dichlorophenyl hydrazono) -6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid ethyl ester, m.p. . 153154 C. - 6-methyl-9- (o-methylphenylhydraerno) -4-oxo-6,7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid ethyl ester, m.p. . 6-methyl-9- (3,4-methylenedioxyphenylhydrazono) -4-oxo-6, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid ethyl ester, m.p. . 172-173 C. 6-methyl-8- (O-nitrophenylhydrazono) -4-oxo-6 i7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid ethyl ester, t .pl. 190192S. B-methyl-9- (and-nitrophenylhydrazono) -4-oxo-6,7,8,9-tetrahydro-4H-pyridino (1,2-a) pyrimidine-3-carboxylic acid ethyl ester, m.p. 218219C. Ethyl ester 9-LА - (amrnosulfonyl) phenyl-giote) azono-3-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, tons square 2iO-213 C. 9- (U1-Brs 1phenylhydrazono) -6-methyl-4-OXO-6, 7,8,9-tetrngydro-4H-pyrido (1, 2-a), Pyrimidine-3-carboxylic acid m.p. 250-252С. 9- (o-Carboxnphenylhydrazono) -6-methyl-4-oxo-6, 7,8,9-tbtrag. Hydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, m.p. 266-268 C. 9- (y1-Chlorofvinylhydrazono) -: 6-methyl-4-OXO-6, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, t .pl. 262-264 C. 6-Methyl-9- (o-methylphenylhydrazono) -4-oxo-6,7,8,9-tetrahydro-4H-pyri-. to (1,2-a) pyrimidine-3-carboxylic acid, so pl. 221-223 C. 6-Methyl-9- (2,6-dimethylphenylhydrazono) -oxo-6,7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carbonoic acid, tons. square 192-193 C. 6-Methyl-9- (2,4,5-trimethylphenylhydraeno) -4-OXO-6,7,8,9-tetrahydro-4H-P5RIDO (1, 2-a) pyrimidine-3 carbonic acid m.p. 224-226. 6-Methyl-9- (2,4,6-trimethylphenylhydrazono) -4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, m.p. . 195-197 C. b-Methyl-9- (2,4-dinitrophenylhydrazono) -4-oxo-b, 7,8,9-heterrahydro-4H-pyrido (1, 2-a) -pyrimide 3-carboxylic acid, m.p. 257-258 C. 6-Methyl-4-oxo-9- (I-sulfophenylhydrazono) -6,7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, t. square above . 9- (I-Etociphenylhydrazono), b-metsh1-4-oxo-A 7 8/9-tetrahydro-4H-pyrido (1,2-a Kirimidine-3-carboxylic acid, mp. 218-219 C. (-) - 9-Phenylhydrazono-6-methyl-4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, mp 258- 259C. (F) -9-Phenylhydrazono-6-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, m.p. 255-256 0. 9-Phenylhydraeno-7-methyl-4-oxo-b, 7,8,9-tetraridro-4H-pyrido (1,2-a pyrimidine-3-carboxylic acid, so pl. 255-25b C. 9- (2-Fluorophenylhydrazono) -6-methyl-4-oxo-b, 7,8,9-tetrahydro-4H-pyridine (1,2-a) pyrimidine-3-carboxylic acid, so pl. 21b -217s. 6-Methyl 9- (2, 4-dichlorophenylhydrazine) -4-oxo-b, 7,8,5-tetrahydro-4H-pyridoC1, 2-a) pyrimidine-3-carboxylic acid, mp 242-244 0. b -Methyl-9- (3,4-dichlorophenylhydraeno) -4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1, 2-a) pyrimidine-3-carboxylic acid, so pl. 248- 250 C. 9- (2-Hydroxyphenylhydrazono) -6-methyl-4-oxo-b, 7,8,9-tetrahydro-4H-pyrido; (1, 2-a) pyrimidine-3-carboxylic acid, t .pl. 252-254 “S. 6-Methyl-9- (3-nitrophenylhydrazono-4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, mp. 268-270 C., 6-Methyl-9- (2-nitrophenylhydrazono-4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxy acid. Lotus, mp 270-274® C. 9- (3-Chlorophenylhydrazono) -b-methyl-4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (i, 2-a) pyrimidine-3-carb6 new acid , mp, 263-265C. 9 - (4-Iodophenylhydrazono7-b-methyl-4-oxo-b, 7.8, 9.-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3- carboxylic acid, mp 245-246 0, 6-methyl-9- (1-naphthylhydrazono) -4-oxo-b, 7,8,9-tetrahydro 4H-pyrido {1, 2-a) pyrimidine-3 - carboxylic acid, etc. 240-242 0. 9- (4-Carboxyphenylhydrazono) -b-methyl-4-oxo-6, 7,8,9-tetrahydro-4Npirido (1,2-a) pyrimidine-3-carboxylic acid, t 280-281 0, b-Methyl-9- (2-methyl-b-chlorophenylhydraeno), - 4-oxo-b, 7,8, 9-tetrahydro-4H-pyrido (1, 2-a) pyrimidine -3-carb new acid, mp. 205-207 0. b-Metnd-9- (3-methylphenylhydrazono, -4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2- a) pyrimidine-3-carboxylic acid, m.p., 242-244 0. (Trifluoromethyl) -phenylhydrazonoZ b-methyl-4-oxo-b, 7,8, 9-tetragro-4H-pyrido (1,2 -a) pyrimidine-3-carb new acid, so pl. 2b8-2b90. (Trifluoromethyl) -phenylhydrazo nb-b-methyl-4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, so pl. 273-274 ° O. 9- (2, b-Diethylphenylhydrazono) -b -methyl-4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2) pyrimidine-3-carbonic acid, m.p. . 1O-1630. 9- (4-Fluorophenylhydrazono) -b-methyl-4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyridine-3-carboxylic acid, m.p. 246-248 0. b-Methyl-9- (4-1-1-methylphenylhydrazono) -4-oxo-b, 7.8, 9-tetrahydro-4H-pyrido- (1,2-a) pyrimidine-3-carboxylic acid / t .pl. 242-244 0 .: 9- (4-Hydroxyphenylhydraeno) -b-methyl 4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, t. square 240-242 0, 9- (2, bt-Dichlorophenylhydrazono) -6-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, mp 230-232 ° O. Hydrate-b-methyl-9- (3,4-methylenedioxyphenylhydrazono) -4-oxo-b / 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, mp . 2262270, 9- (4, -Acetylphenylhydrazono) -b-methyl-4-OXO-6, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, so pl. 245-2470. b-Methyl-9- (2-methoxyphenylhydrazono) -4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, m.p. 21b-2180. b-Methyl-9- (4-methoxyphenylhydro-zono) -4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (l, 2-a) pyrimidine-3-cannabis acid, so pl. 212-214C. 9- (4-Bromo-2-chlorophenylhydrazono) -. -6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido (1, 2-a) pyri / IIDIN-3 carbox novoy acid, so pl. 245-247 0. 7-methyl-9-phenylhydrazono-4-oxo-6 ethyl ester, 7,8,9-tetrahydro-4H-pyrimide (1, 2-a) pyrimidine-3-carboxylic acid, m.p. 1b5-1670, 8-methyl-9-phenylhydrazono-4-oxo-b ethyl ester, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine - 3-carboxylic acid, m.p. 108-110o. 9-Phenylhydrazono-2, b-dimethyl-4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxamide, so pl. 235-237 0 .: Ethyl-9-phenylhydrazono-b-methyl-4-oxo-b, 7, 8,9-tetrahydro-4I-pyrido (1,2-a) pyrimidine-3-yl-acetate, t .pl. 100-102 C. 9-Phenylhydrazono-b-methyl-4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidin-3-yl-acetic acid, so pl. 1bO: 1b20. . 9-fenilgndraeono-b-methyl-b, 7,8,9-tetrahydro-4H-pyrido 1, 2-a) pyrimidine-4-OH, so pl. 1b3-1b50. This ester is EE- (phenylhydrazono) -b-methyl-4-oxo-b, 7,8, 9-tetragon: .1dro74H-pyridyl (1,2-a) pyrimidin-3-yl-IROPIONIC ACIDS., T.PL . .
    9- (Phenylhydrazo o) -8-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyryl (1,2-a) pyrimidine-3-carboxylic acid, T.PL. 234-236 0.
    6-Methyl-9- {4-nitrophenylhydrazono) -4-OXO-6, 7.8, 9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, T.PL. 242-244 C.
    9- (3-carboxy-3-chlorophenylhydraenone) -6-methyl-4-oxo-6,7, 8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid monohydrate, T. Submarine 275-276 C.
    9- (Phenylhydraeno) -6-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3- (N-methylcarboxamide), T.PL. 153-154 C.
    2-Sb-Methyl-4-oxo-b, 7,8,9-tetragtsdro-4H-pyrido (1,2-a) pyrimidine-9-y Lidehydrazono-benzoic acid, T.PL. 170-172EUR
    3-b-Methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidin-3-ylidene hydraone-3-benzoic acid, T.PL. 260-262 C.
    9- (4-Biphenylhydrazone) -6-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido- {1, 2-a) pyrimidine-3-carboxylic acid, T.PL. 160-162 ° C
    9- ("-Phenoxyphenylhydrazono) -b-methyl-4-OXO-6, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic Acid, T.PL. 220-222C.
    9- (2-Naphthylhydrazono) -6-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, T.PL. 172-174 C.
    9- (2 | -Carboxy-3-naphthylhydrazono) -b-methyl-4-oxo-b, 7,8,9-tetrahydrone-4H-pyrimidine-1-2-a) pyrimidine-3-carboxylic acid, T .PL 260-262 C.
    9- (4-Ethylphenylhydrazono) -6-methyl74-OXO-6, 7,8,9-tetrahydro-4H-pyrido {1, 2-a) pyrimidine-3-carboxylic acid, T.PL. 208-210 0.
    9- {4-Cyanophenylhydrazono-b-meGIL-4-OXO-6 7,8,9-tetrahydro-4H-pyRido (1,2-a) pyrimidine-3-carboxylic acid, T.PL. 223-225 C.
    9- (2-Acetylphenylhydrazono) -b-me-, TIL-4 - OXO-6,7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, TP PL . 245-246 0.
    9- (3-Acetylphenylhydrin azrnr) -6-methyl-4-OXO-6, 7,8,9-tetrahydro-4H-pyrimidine (I, 2-a) pyrimidine-3-carboxylic acid, TP. 238-240 0.
    6-Methyl-9- (i-trifluoromethylphenylhydrazono) -4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, T.PL. 238-240 0.
    9- (2-Chlorophenylhydrazono) -b-methyl-4-oxo-b, 7,8,9-tetrahydro-4H-gyrrido (1,2-a) pyrimidine-3-carboxylic acid, T.PL. 2b-2b2 S.
    9- (2-Bromophenylhydrazono) -b-methyl-4-OXO-6, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, T.PL. 265-267 0.
    9- (3-Bromophenylhydrazono) -6-methyl-4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, T.PL. 260-262 0.
    9- (2-Iodophenylhydrazono) -b-methyl-4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (, 2-a) pyrimidine-3-carboxylic acid, T.PL. 246-248 0.
    0 9- (3-Iodophenylhydrazono) -b-methyl-4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, T.PL. 258-260 0.
    9- (3-Carboxyphenylhydrazono) -b-me5-4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1.2-a) pyrimidine-3-carboxylic acid, T.PL. 263-265 0.
    9- {2-Ethoxyphenylhydrazono) -6-methyl-4-OXO-6, 7,8,9-tetrahydro-4HQ-pyrido (1,2-a) pyrimidine-3-carboxylic acid, T. PL. 225-227 C.
    9- (3-Ethoxyphenylhydrazono) -b-methyl-4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, T.PL. 210-211 0.
    (+) - 9- (4-Ethoxyphenylhydrazono) -6-methyl-4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, TP. . 208--209O.
    (+) - 9- (2-Carboxyphenylhydrazono) -6-methyl-4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, TP. . 260-261 0.
    () 9- (2-Carboxyphenylhydrazono) -6-methyl-4-oxo-b, 7,8,9-tetrahydro5 -4H-pyrido (1,2-a) pyrimidine-3-carboxyl acid, T.PL. 2b1-2b2 0.
    () -9- (4-Chlorophenylhydrazono) -b-methyl-4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid, m.p. . 255-256 0.
    Example 3. To 780 ml of methanol was added 80.0 g (0.28 mol) of 9-bromo-6-methyl-4-oxo-6, 7,8,9-tetrahydro2-h4H-pyrido (1, 2-a ) pyrimidine-3-carboxylic acid, then 15.5 ml of a 50% aqueous solution of hydrazine hydrate are quickly added to the suspension. Re: The stock mixture is heated and transferred to a clear solution. Solution
    0 at room temperature is stirred for 2-3 hours, then the precipitated crystals are filtered off. The separated hydrazonium mixture is dissolved in 400 ml of water and acid is added by the addition of an equivalent amount of potassium hydrosulfonate. The precipitated crystals are filtered, washed with a small amount and then dried. After recrystallization from 50% aqueous ethanol, 40.2 g (60.3%) of 9-hydraeono-b-methyl-4-kso-b, 7,8,9-tetrahydro-4H-pyrido (1,2 -a) pyrimidine-3-carboxylic acid, which melts at
    5 202-203 “0.
    Elemental analysis.
    Calculated,%: C 50.84; H 5.12; N 23.72.
    Found,%: C 50.46; H 5.30; N 23.68.
    Example 4. To a solution of g (12.73 mmol) of ethyl 9-bro-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-PYRIDO (1,2-a) pyrimidine-3- carboxylic acid in 20 ml of ethanol while stirring, 8 ml of a 50% aqueous solution of hydrazine hydrate is added dropwise. The thief is stirred at room temperature for 2 hours. The precipitated crystals are filtered, washed with a small amount, ethanol and then dried. After recrystallization from ethanol, 1.6 g (50.2%) of 9-hydrazono-6-methyl-4-oxo-6, 7,8,9-tetrahydropyrido (-1 i 2-a) pyrimidine-3- are obtained. carbohydrazide, which melts at 219220 ° C.
    Example 5. 10, O g
    (34.95 mmol) 9-brcc4-6-methyl-4-oxo 6,7,8,9-tetrahydro-4H-pyrido (1,2-a pyrimidine-3-carboxamide is dissolved in 150 ml of methanol with heat. 20 ml of hydrazine hydrate are added dropwise to the solution with stirring for 10 minutes, the reaction mixture is boiled for 40 minutes and then methanol is distilled off in vacuum. The crystals are filtered, washed, washed with water and then recrystallized from water. 46.5%) 9-hydrazonob-methyl-4-oxo-6, 7, 8,9-tetrahydro-4H-pyrido (1,2a) pyrimidine-3-carboxamide, which melts at 248250 ° C.
    Elemental analysis.
    Calculated,%: C 51.06; H 5.57; N 29.77.
    Found,%: C 50.59; H 5.46; N 29,85.-.
    Primer, p 6. To a solution prepared with 20 ml of methanol, 2.9 g (0.01 mol) of 9-bromo-6-methyl-4-oxo b, 7,8,9 ttetrahydro-4H-pyrido (1, 2-a ) pyrimidine-3-carboxamide, 0.025 mol of p- (N, N-diamethylamino) benzaldehyde hydrazone is added. The mixture is stirred and boiled for 1-3 hours with stirring. 6-methyl-9 4- (N, N-dimethylamino) -benzylidenehydrazono-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido (1 , 2-a) pyrimidine-3-carboxamide, which melts at 220-222 C.
    Elemental analysis.
    Calculated,%: C 62.28i.H, 6.05; N 22.98.
     “Yy 6 Oh
    Found,%: C 62,12; H 6.00;
    N 22.87.
    Example 7. Work according to the method described in example 6, however, methylhydrazine is used as a hydrazine derivative. A 40% yield of 6-methyl-9-methylhydrazno-4-oxo-6, 7,8,9-tetrahydro-4H-pyrdo (1,2-a) pyrimidine-3-carboxamide, which melts at 228-230Ci, is obtained.
    Elemental analysis
    Calculated,%: C 53.00; H 6.06; N 28.09.
    %% 0 2
    Found,%: C 52.57 H 6.03; N 28.00.
    Example 8. Work according to the method of example 6; however, it comes from 2-caprolactamhydrazone. 55% yield of 9- (2-azepinylidenehydrazone) -6-methyl-4-oxo-6,7,8,9 tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxamide is obtained, which melts at 228-2300C.
    Elemental analysis.
    Calculated,% s C 58,16; H 6.71 N 25.43.
    .% 02
    Found,%: C 58,12; H 6.57;
    N 25.41.
    Example 9. To a solution prepared with 20 ml of methanol, 2.9 g (0.01 mol) of 9-bromo-6-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido (1, pyrimidine 0.025 mol of methylhydrazine is added to the 3-sarboxylic acid. The reaction mixture is heated under stirring for 1-3 hours. A 25% yield of 6-mhthyl-9-methylhydrazono-4-oxo-6, 7,8,9-tetrahydroxy is obtained. 4H-pyrido (1, 2-.a) pyrimidine-3-carboxylic acid, which melts at 216 - ,, 218 C,
    Elemental analysis.
    Calculated,% g C 52.79; H 5.62; N 22.38,
    C H H4% 02.
    Found,%: C, 51.99; H 5.49.
    N 22.28.
    Example 10 The method is as described in Example 9, however, it is derived from 8-caprolactic hydrazone. A 40% yield of 9- (2-azepinylidenehydrazono) -6-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido (1,2-a pyrmidine-3-carboxylic acid, which is melted at 166-170®С.
    Elemental analysis.
    Calculated,% 5 C 57.99; H 6.38; N 21.13.
    C feHlfNg-O
    Found,%: C 57.82; H 6.29; N 21.10.
    EXAMPLE 11.5.7 g ((o, 2 mol 9-bromo-6-methy.71-4-oxo-6,7,8, 9-tetrahydro-4H-pyrJ to {1, 2-a ) pyrimidic-3-carboxylic acid is dissolved in 30 ml of anhydrous ethanol and 4.3 ml of 30.044 mol of phenylhydrazine is added. The reaction mixture is heated under reflux with stirring for 4 hours, after which crystals are filtered and washed with ethanol. 4.7 g (75.2%) are obtained in this way. 9- (phenylhydrazono) -6-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido (1,2-a pyrimidine-3 -carboxylic acid, t, pl., 258-2 VOC After recrystallization from dimethylformamide, the temperature melting increases to 267268 ° C. Example 12. The same operations are carried out in the same sequence as in Example 11, but using (-) - 9-bromo-b-methyl-4-oxo-6,7,8, 9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-8-carboxylic acid -45 ° (Cr1, methanol). In this way (+) -9- (phenylhydrazono) -6-methyl-4-OXO is obtained. -6,7,8,9-tetrahydro-4H-pyridine (1,2-a) pyrimidine 3-carboxylic acid. Output 76.0%, so pl. 256-257C Cd-J | j + 407.5 (, dimethylformamide). Example 13. In accordance with Example 2, but replacing the phenylhydroxide of Razin with N-aminopiperidine, evaporating the reaction mixture in vacuo, dissolving the residue in methanol and adding 0.15 ml. 70% by weight of perchloric acid, with final filtration for precipitating crystals washed with methanol, I get p-chloro 6-methyl-9- (1-piperidioimo) -4-oxo-b, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine -3-carboxylic acid, melting at 167-178 ° C. The yield is 53.7%. Elemental analysis. Calculated,%: C, 44.51; H 5.23; N 13.84; every 8,78. seo4 Found;%: C 44.20} H 5.21; N 13.81; All 8.91. Example 14 According to Example 2, but replacing phenylhydrazine with 2-hydrazinopyridine and recrystallizing the crude product from acetonitrile, 6-methyl-9- (2-pyridylhydrazone) -4-hydroxy-6,7,8,9-tetrahydro 4H-pyrido ( 1, 2-a-) pyrimidine-3-carboxylic acid, m.p. 233-234 ° C. The yield is 66.2%. Elemental analysis. Calculated,%: C 57.50; H 4.83; N 22.35. S.g H.g. NC-OI; Found,%: CJ 57.83; H 4.86; N 22.05. Example 15. To a solution of 0.6 (0.015 mol) of sodium hydroxide in 25 ml of water was added 3.4 g (0.01 mol of ethyl ester of 9- (phenylhydrazoyo) 6-methyl-4-oxo-b, 7.8, 9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid. The suspension is stirred at 50-60 ° C for 4-5 hours and all components are dissolved in the solution. Diluted 1: 1 with aqueous hydrochloric the acid is adjusted to a pH of the solution equal to 2. The precipitated crystals are filtered and washed with a small amount of water to give 2.1 tons (86.4%) of 9- (phenylhydrazono) -6-methyl-4-OXO-6, 7.8,9-tetrahydro 4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid s which melts at 267268 C. Example 16. In suspension 34.0 g (0.14 mol) of 9-hydrazono-6-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido (1 , 2-a) pyrimidine-3-carboxylic acid, 700 ml of anhydrous ethanol at 10-15 ° C. And dry hydrogen chloride is added with stirring. After saturation of the solution, it is left to stand overnight in a refrigerator. The next day the solvent is distilled off under reduced pressure. The residue is dissolved in 50. ml of water. The solution is neutralized with a 5% aqueous soda solution and extracted with 4i100 ml of chloroform. The combined organic phases are dried over calcined sodium sulphate and then evaporated in vacuo. The residue is recrystallized from methanol. 18.0 g (48.6%) of 9-hydrazono-6-methyl-4-oxo-6 ethyl ester are obtained; 7,8,9-tetrahydro-4H-pyrido (1, 2-a) pyrimidine-3-carboxylic acid, which melts at 199-200 ° C. Elemental analysis. Calculated,%: C 54.54; H 6.10; N 21.20. C-fi Noob 4 0 Found,%: 53.88; H 6.20; N 21.10. Example 17. A suspension of 2.0 g (7.57 mmol) of 9-hydrazono-6-methyl-4-ox-6-6, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine ethyl ester 3-carboxylic acid and 20 ml of ethanol are brought to a boil and mixed dropwise with 4 ml of a 50% aqueous solution of hydrazine hydrate. After boiling for 15 minutes, a solution is obtained from which crystals are precipitated upon cooling of the egg. The crude product is recrystallized from methanol. 1.0 g (52.8%) of 9-hydrazono-6-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carbohydrazide is obtained, which melts at 219-220 s. Elemental analysis. Calculated,%: C, 47.99; H 5.64; N 23.58. Cyg, Found,%: C 48.43; H 5.67; N 23.59. Example 18. To a solution of 2.0 g (7.57 mmol) of 9-hydra-6-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine ethyl ester -3-carboxylic acid in 20 ml of anhydrous chloroform was added 1.6 ml, (11.35 mol) of triethylamine and 1.3 ml (11.35 mmol) of benzoyl chloride. The mixture is boiled for 2 hours, then cooled to room temperature and basicly shaken with 20 ml of water. The organic phase is separated, the aqueous phase is extracted with 10 ml of chloroform. The combined organic phases are dried over calcined sodium sulphate and then evaporated in vacuo. The residue is recrystallized from methanol. 1.5 g (53.8%) of 9- (benzoylhydrazono) -6-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido- (1, 2-a) pyrimidine are obtained -3-carboxylic acid, which melts at 209-210 s
    Elemental analysis.
    Calculated,%: C, 61.96; H 5.47; N 15.20.
     From 9 th 4- ° 4Found,%: C 62.02; H 5.58;
    N 15.61.
    Example 19. To 12 ml of dimethyl sulfoxide was added 2.0 g (7.57 mmol) of 9-hydrazono-6-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido ethyl (1,2 a) pyrimidine-3-carboxylic acid. Suspension is mixed with 1.2 ml (11.88 mmol) of benzaldehyde. The reaction mixture is left to stand at room temperature for 4-6 days, during which time a solution is formed. The solution is diluted with 20 ml of water and shaken with ml of benzene. The combined organic phases are dried over calcined sodium sulfate and evaporated under reduced pressure. A dark-colored oil remains, from which crystals are precipitated by the addition of 25 ml of diethyl ether. The crystals are filtered and washed with a small amount of ether. Obtain 2.0 g (75fO%) of the product. The final product is a mixture of isomers. Isomers are separated by preparative thin layer chromatography on a plate with a layer of silica gel (cm, layer thickness 1.5 ml, silica gel 60 Pp 254366), and the benzene-methanol mixture E is the ratio 7: 1, and the solvent is a methanol dichloromethane mixture in a ratio of 1:10.
    The substance with the highest R value is 9- (enhydrazino benzylide) -b-methyl-4-oxo-6, 7-dihydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid ethyl ester. After recrystallization from methanol, 0.12 g of product is obtained, melting at 142-144 C.
    Electronic analysis.
    Calculated,%: C 64.77; H 5.72; N 15.89.
     From N40%
    Found,%: C 64.70; H 5.85; N 15.73.
    The substance with the lowest value of R {is the 9- (benzylidene hydrazono) -6-methyl-4-oxo-6,7 ethyl ester of 8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid. After recrystallization from methanol, 0.75 g of melting powder is obtained at. 133134С product.
    Elemental analysis.
    Calculated,%: C 64.77; H 5.72; 15.89.
    S.RN
    Naadro%: C 64.43;
    H 5.53; 5 N 15.82.
    Example 20. 7.8 g (O, O 2 mol; 9-phenylhydrazono-6-methyl-4-oxo-6 ethyl ester; 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine); The 3-carboxylic acid of the new acid is dissolved in 100 ml of ethanol. The solution is mixed with 6.0 ml of 98% hydrazine hydrate and then boiled under reflux for two hours. The crystals begin to precipitate on cooling. The crystals are filtered and washed with ethanol. 4 g (82.7%) of 9-phenylhydrazono-6-methyl-4-OXO-6, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carbohydrazide, which melts at 205 -207®С, Elemental analysis. Calculated,%: C 58.89; H 5.56;
    N 25.75.
     H- / 0 6 Oi
    Found,%: C 58.06; H 5.47j N 25.52.
    For example 21. To a solution of 2.15 tons (0.036 mol) of potassium hydroxide in 50 ml of water was added 4.3 g (0.012 mol) of ethyl 9- (phenylhydrazono) -6-methyl-4-oxo- 6.7, 8,9-tetrahydro-4H-pyrido (1,2-a) pyrimyin-3-yl3 acetic acid and the resulting mixture is stirred at room temperature for 4 hours. The value of 5 PH of the solution is set at 3 with 10% - by weight hydrochloric acid solution. The precipitated crystals are filtered off and washed with water. 2.95 g (75.6%) of 9- (phenylhydrazono) -b-methyl-4-OXO-6, 7,8,9-tetrahydro-4H-pyrido (1,2-a) are obtained. ) pyrimidin-3-yl} acetic acid, melting at 161162 ° C.
    Example 22. a solution of 2.1 g of ethyl ether 9- (4-methylphenylsulfonyl) - (oxyimino) -6-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido (1, 2-a) pyrimidine-3-carboxylic acid and 1.08 g of fequylhydrazine in 40 ml of toluene are boiled for 1 hour. The reaction mixture is cooled to room temperature and the precipitated crystals are filtered. The filtrate is evaporated under reduced pressure and the residue is dissolved in 7 ml of 30%
    (weight / volume) solution of hydrogen chloride in methanol. The precipitated hydrochloride is filtered off, suspended in 100 ml of water, and the pH of the solution is adjusted to 8 using 20% w / v sodium carbonate solution. The oil precipitated phase crystallizes when the glass rod is scratched along the walls of the vessel. The 1,4-ethyl ester of 9- (phenylhydrazono) -6-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-PIRIDO (1,2-a) pyrimidine-3-carboxylic acid, crystallized with 1, is obtained. mole of ethanol. The product melts at 80-82 ° C. The aqueous phase is shaken with chloroform, the solution is dried and evaporated to obtain an additional amount of 3.3 g of product. After recrystallization, 1.7 g of product from 20 ml of ethyl acetate is obtained 9- (phenylhydrazono) ethyl ester -6-methyl-4-oXo-6,7,8,9-tvtrahydro-4H-pyrido (t, 2-a) pyrimidine-3-carboxylic acid, melting at 137 D39C.
    Example 23 2.2 g (0.01 mol) of 9-hydroxy-b-methyl-4-oxo-6,7-dihydro-4H-pyrido (1,2-a) pyrimidine-3-carboxylic acid is dissolved in 15 ml of anhydrous ethanol and 1.2 ml (O, 012 mol of phenylhydrazine) are added to the resulting solution. The reaction mixture
    heated under reflux with stirring for half an hour; Crystals dropped by the atom are filtered off and washed with ethanol. In this way, 2.4 g (76%) of 5 9- (phenylhydrazono) -6-methyl-4-oxo-6, 7,8,9-tetrahydro-4H-pyrido (1) pyrimidine-3-carboxylic acid are obtained with t .pl. 267-2b8 C (from dimethyl formamide).
    0 Example. 24. To 20 ml of acetone was added 0.5 g of 9- (phenylhydrazino) -b-methyl-4-oco-6, 7, 8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3- carbohydrayl. The reaction mixture was boiled at 5 t for 3 h with vigorous stirring; 1 and. After that, the mixture is cooled, the precipitated crystals are filtered and washed with acetone. .0.35 g of M-isopropylidene-90 - (phenylhydrazono) -6-methyl-4-oxo 6, 7,8,9-tetrahydro-4H-pyrido (1,2-a) pyrimidine-3-carbohydrazide, melt at 293-295 ° C after recrystallization from a mixture of chloroform and ethanol.
    five
    Elemental analysis. Calculated,%: C, 62.29; H 6.05) N 22.93.
     N "OI
    权利要求:
    Claims (1)
    [1]
    Found,%: C 62.29; H 6.14; N 23.10. Claims method for producing derivatives pi | arid (1, 2-a) pyrimidine of the general form-1 O where R, is an ATS and hydrogen or lower alkyl; hydrogen atom or lower alkyl J carboxyl, LOW alkoxycarbonyl, carbamoyl, carbohydrazido group, —CONHNsC {CK ,,) a group or r-fCH) w -COORg group, where Rg is a hydrogen atom or lower level, and W 1, or 2; hydrogen atom, lower alkyl, phenyl, optionally substituted by one or more identical substituents selected from the group consisting of halogen atoms / lower alkali, nitrocarboxyl, hydroxyl group, trifluoromethyl syxoxy, sulfate, sulfonamide, low apkanoyl, phenyl, phenyl, sulfonic acid, sulfonamide, low apkanoyl, phenyl, phenyl, sulfonic acid, sulfonamide, low apkanoyl, phenyl, phenyl, sulfonic acid, sulfonic acid, sulphonic acid, sulfonic acid, sulfonic acid, hydroxylic acid , cyanoyl or methylideioxy groups} / or naphthyl, possibly substituted by a carboxyl group, or benzoyl} hydrogen, or Kj and Rf together with the nitrogen atom with which they are attached, form a pyridine group or group Sigr), or a group -NsC RgR7f D®% hydrogen or lower alkyl (R) lower alkyl, phenyl, or di (lower) gshkylaminophenyl / or their pharmaceutically acceptable salts, or their optically active isomers, characterized in that the compound of formula II or its tautomer forms, or optically active isomers, where the dotted lines are possible additional communication; R-Rj have the indicated meanings; L is a halogen, hydroxyl or p-toluenesulfonyloxyamine group, is reacted with a compound of the general formula 111 where RI and Rg. have the indicated values, nor, ....;. followed by isolation of the desired product or saponification of the resulting ester, or subsequent conversion of the resulting acid to the corresponding ester, amide or hydrazide, or subsequent benzoylation of the resulting compound of formula I, where Rj |. - hydrogen, followed by separation of the target products, or followed by the subsequent synthesis of the obtained compound of formula I,. where R and Ry are hydrogen atoms, with a compound of the general formula) Rf, where RgH R have the indicated meanings, and the target products are isolated in free form or in the form of pharmaceutically acceptable salts, or as optically active isomers. Sources of information taken into account during the examination 1. Weigand-Hilgetag. Experimental methods in organic chemistry. M., Himi, 1968, p. 426.
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    同族专利:
    公开号 | 公开日
    PL228812A1|1981-12-11|
    FI804017L|1981-06-30|
    FI64736B|1983-09-30|
    IT1195200B|1988-10-12|
    CS226420B2|1984-03-19|
    NL8006957A|1981-08-03|
    ATA632280A|1981-12-15|
    HU184622B|1984-09-28|
    AT367600B|1982-07-12|
    CH646034A5|1984-11-15|
    US4364931A|1982-12-21|
    GB2066666A|1981-07-15|
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    DK553780A|1981-06-30|
    GB2066666B|1983-08-17|
    ES498615A0|1982-07-01|
    FI64736C|1984-01-10|
    SE8008943L|1981-06-30|
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    IT8026979D0|1980-12-29|
    FR2472340A1|1981-07-03|
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    法律状态:
    优先权:
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    HU79EE2721A|HU184622B|1979-12-29|1979-12-29|Process for preparing 7/z/-dodecen-1-yl-acetate|
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