• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    The invention relates to a process for the preparation of novel 1,2,4-triazin-5-one derivatives of general formula I in which Het ', Z', Y and χ have the meaning given in the invention claim, and their salts with acids , Hydrates and hydrate salts. These compounds are histamine Hi and H2 receptor antagonists. - Formula I
    公开号:SU733517A3
    申请号:SU782594701
    申请日:1978-03-17
    公开日:1980-05-05
    发明作者:Генри Браун Томас；Джон Айф Роберт
    申请人:Смит Клайн Энд Френч Лабораториз Лтд (Фирма)；
    IPC主号:
    专利说明:

    one
    This invention relates to a process for the preparation of novel triaenones of general formula I
    2
    ly I, enclosed in a triazinone of the general formula II
    ABOUT
    on. (lft, Y
    III
    Dt
    Het - CHg- S - (H7- (Hf-m- -y
    I
    n
    where Hat is indispensable or substituted by bromine or methyl 2- or -4-imidazolyl or 2-thiazolyl or 3-isothiazolyl, U-pyridyl or M-methoxyphenyl,
    which can be used in medicine.
    It is known that the interaction of S-alkyl-isothiuronium salts with ammonia or amines to obtain guanidines 1.
    The aim of the invention is to obtain new triazinones with improved properties.
    The goal is achieved by the fact that according to the proposed method of producing triazinones, the general formula where Y has the meanings indicated above is reacted with an amine of the general formula III
    IS
    Het-CH, -.- CH2-CH2-NH, 2.,
    in which Het is as defined above.
    Example 1. (5-methyl4-imidazalylmethylthio) -ethylamino b- (3-methoxybenzyl) -1,2,4-triazin5-one.
    1 / 25.9 g of t-anisaldehyde, 15.2 g of N-acetylglycine and 7.8 g of acetate
    Sodium 25 is co-boiled using a reflux condenser in 50 ml of acetic anhydride for 3/4 h. The mixture is then cooled, 150 ml of water are added and the mixture is filtered. Obtain 27.7 g of crude azalactone with so pl. 145 150s Hydrolysis using 450 ml of boiling normal hydrochloric acid followed by cooling and ether extraction yielded 6.3 g of 3-methoxyphenylpyruvic acid as a pale yellow oily solid. P / 2.1 g of 3-methoxyphenylpyruvic acid, 0.98 g of thiopaccharide, baside, and 1.5 g of sodium oxide crescent are kept at 70–75 ° C in 30 ml for 1 hour. An oil-like product is obtained by cooling and acidification. which is subjected to chromate graphic analysis to obtain 6- (3-methoxybenzyl) -1,2,4-triazin3-thio-3, 5-dione as a pale yellow solid, recrystallization from a mixture of ethyl acetate and benzene gives pure .pl.140-141. product with C 53.1; H 4.6; Found,% N, 16; S 12,6 CHI -ii Calculated,%: C 58.0; H 4.5; N 16.9; S 12.9. Ill / 0.34 g of sodium was dissolved in 25 ml of ethanol, 3.5 g of 6- (3-methoxybenzyl) -1,2,4-triaziv3-thio-3, 5-dione was added and the solution was cooled on ice. Then 2.1 ml of methyl iodide are added and the mixture is stirred at room temperature for 1 hour, after which an additional 0.5 g of methyl iodide and sodium ethoxide solution (equivalent to 0.05 g of sodium) are added. The mixture is cooled overnight and filtered to give 2.5 g of 3-methylthio-6- (3-methoxybenzyl) -1, 2-4 -Triazin-5-it with so pl. 185-186 C. By evaporating the mother liquor to dryness and treating the residue with dilute hydrochloric acid, an additional product is obtained. ly / 1.07 g of 3-methylthio-6- (3-labels, benzene) -1,2,4 triazi-5-one and 0.77 (5 methyl-4-imidazolylmethylthio) -ethyl amine are kept on an oil bath at 160-170 ° C for 3/4 h. The solidified mass is chopped in methanol (approximately 15 ml) and boil for 5 minutes. After cooling, the white substance is filtered and recrystallized from dimethylformamide to obtain the compound indicated in the table of contents as an example of a colorless solid (0.65 g with T .. PL., 203-204 C. Found.% 55.7; H 5.7; N8.3; S21.7; G e% 2% ° 2 C 55.9 H 5.7; calculated 5 N 21.8; S 8.3. 2. (( 2-thiazols Example I:; ylthio) -ethylamino-6- (8-methoxybenzyl) -1,2,4-triazin-5on 1.18 g H-methylthio-6- (3-methoxybenzyl) -1, 2, 4-triazin-5-one and 0.87 g of 2- (2-thiazalylmethylthio) -ethylamine are subjected to simultaneous exposure with heating in an oil bath at 160-170 ° for 3/4 h. After chromatographic processing and crystallization from ethanol of the final oil-like product gives 0.88 g of the compound indicated in the table of contents, for example, in the form of a colorless solid product with mp 128 289 ° C. Found: C 52.4; H 5.0 ; 18.0; S 16.6., C 52.4; H 4.9; Calculated,% N 18.0; S 16.5. (5-methyl-4; Example imidazolylmethylthio) ethylamino -6 (3- pyridylmethyl) -1, 4-triazin-5-one. T / 92.6 g pyridine-3-carboxaldehyde, 86.0 g acetylglycine and 35.3 g sodium acetate together are refluxed in 150 ml acetic acid anhydride over 1 hour. After cooling, 250 ml of water are added and the mixture is filtered with Acquiring 50.9 g of crude azlactone with t.pl.155160 °. Partial hydrolysis of 50 g of azlactone, m.p. 155-160 ° C is heated by boiling at reflux into 450 ml of acetone and 175 ml of water for 4 hours. At the end of this time, the bulk of the adeton is distilled and an additional 300 ml of water is added. The final dark red solution is boiled with charcoal for 10 m and filtered through celite. The filtrate is evaporated to dryness, and the residue is triturated and washed in acetone to obtain 2-gscetamido-3- (3-pyridyl) acrylic acid (35 g) with mp 191192 ° C, which is not further purified. P / 10.3 g of 2-acetamide-3- (3-pyridyl) acrylic acid and 4.55 g of thiopolucarbazide are kept at reflux with 50 ml of water for 42 hours. The mixture is cooled and filtered. Get 6- (3-pyridylmethyl) -1,2-4-triazin-Ztio-3, 5 dione (7,22 h) with so pl.280 With (decomp.) In the form of a pale brown solid. 111 / 1.73 g of sodium was dissolved in 40 ml of ethanol, 6.6 g of 6- (3-pyridylmethyl) -1,2,4-triazine-Ztio-3, 5-dione was added and the mixture was cooled on ice. Then 5.0 g of methyl iodide is added and the mixture is stirred for 30 m at room temperature. After evaporation to dryness, the residue is dissolved in 50 ml of water, the solution is filtered and the pH of the solution is adjusted to 6-7, and then cooled overnight. The resulting creme-like solid was removed and recrystallized from methanol. 5.86 g of 3-methylthio-6- (3-pyridylmethyl) -1,2,4-triazin-5-one are obtained with m.p. 215-21b C, 1U / 2.34 g of 3-methylthio-6- (3-pyri, dilmethyl) -1,2,4-triazin-5-one and 2- (5-. Ethyl-4-imidazolylmethylthio) ethyl (1.88 g), heating wells in an oil bath up to 160-170 s. The cooled mixture is triturated in boiling methanol and the product obtained is recrystallized from dimethylformamide to obtain the compound indicated in the table of contents, for example, as a colorless solid (2.53 g) with m.Sh1.232-233s. Found,% S With 53.7; H 5.4; N 27.3; S 8,8. : C 53.8; H 5.4; Calculated,% N 27.4; S 9.0. 4. (2-thiazols Example of methylthio) -ethylamino-6- (3-pyridylmethyl) -1,2,4-triazin-5-one. H-methylthio-6- (3-pyridylmethyl) 1, 2,4-triazin-5-one, (3.28 g) and 2.7 2- (2-thiazalylmethylthio) -ethylamine are together kept in an oil bath at 160 -170 s for 1 h. The cooled mixture is triturated in isopropanol, and the solid product is subjected to double recrystallization from ethanol. 3.1 g of the title compound, for example, are obtained in the form of light yellow plates with mp 158-159 ° C. Found,%: C 50.0; H 5.6; N 23.5; S 17.6. N S2 In Lt Number,%: C 50,0; H 4.5; N 23.3; S 17.8. Example 5. (3-bromo-2 pyridylmethylthio) -ethylamino b- (3-pyridyl-methyl) -1,2,4-triazin-5-one. As a result of the replacement of 2- (3-bromo2-pyridylmethylthio) -ethyl-amine with 2- (5-methyl-4-imidazolylmethylthio) -e amine, which was used during experiment 3 (IV), the product indicated in the heading of the Institute for example. Example 6. (3-Bromo-2iridylmethylthio) -ethylamino-6- (3-methoxybenzyl) -1,2,4-triazin-5-one. Using 2- (3-bromo-2-pyriylmethylthio) -ethylamine instead of 2- (5methyl-4-imiyazolylmethylthio) -ethylmine, which was used during the experimental procedure of example (IV), allows to obtain the compound indicated in the table of contents of the invention Formula the preparation of triazinones in the formula I ... -m, -s- "rtHriffl Het-Cliz de Het - unsubstituted or substituted by bromine or methyl 2- or 4-imidazolyl or 2-thiazolyl or 3-isothiazolyl; Y is pyridyl or M-methoxyphenyl, which means that the triazinone of the general formula II. A (li de V has the meanings indicated above, subject to interaction with an amine of the general formula: Het-CH, -e-OH2-cH2-HV 2, wherein the Het has the abovementioned. Sources of information taken into account in the examination 1. Weigand-Hilgetag. Experimental methods in organic chemistry,., Himi, 1968, 0.512.
    权利要求:
    Claims (2)
    [1]
    Claim
    Het
    A method for producing triazinones of the general formula I wherein Het is 2- or 4-imidazolyl or 2-thiazolyl or 3-isothiazolyl unsubstituted or substituted with bromine or methyl;
    U is pyridyl or M-methoxyphenyl, which concludes that the triazinone of general formula II
    Found,%: C 50.0; H 5.6;
    N 23..5; S 17.6.
    C 45 H 46 N 6 S 2
    Calculated,%: C 50.0; H 4.5; N, 23.3; S 17.8.
    Example 5. 3— [2— (3 — bromo — 2 — pyridylmethylthio) ethylamino] b- (3pyridylmethyl) -1,2,4-triazin-5-one.
    As a result of the replacement of 2- (3-bromo
    2-pyridylmethylthio) ethylamine
    [2]
    2- (5-methyl-4-imidazsilylmethylthio) -ethylamine, which was used during experiment 45 (1U), gives the product indicated in the table of contents for example.
    where Y has the meanings indicated above, is reacted with an amine of the general formula
    Het-CH 2 -'3-cM 2 - CH 2 ' NV ' 2 '' in which Het has the above meanings.
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US4309435A|1978-10-16|1982-01-05|Imperial Chemical Industries Ltd.|Antisecretory guanidine derivatives and pharmaceutical compositions containing them|
    US4394508A|1980-06-07|1983-07-19|Bristol-Myers Company|Chemical compounds|
    AU2192683A|1982-12-30|1984-07-05|Biomeasure Incorporated|Pyrazolo-1,3,5-triazines|
    GB0113343D0|2001-06-01|2001-07-25|Bayer Ag|Novel Heterocycles 2|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    GB11757/77A|GB1601132A|1977-03-19|1977-03-19|Pharmacologically active triazinones|
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