• 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:
    These are described compounds of formula (I) or an acid addition salt thereof; in which R1, R2, R3 and R4 independently represent hydrogen, C1-4 alkyl, C2-4 alkenyl, halogen, C1-4 haloalkyl, nitro, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 alkylthio or phenylsulphonyl; in which R5 is a group of the formula where R7 is hydrogen or C1-6 alkyl, R8 is hydrogen or C1-4 alkyl and n is 0 or 1, provided that when R7 is hydrogen n is 0; and in which R6 is attached to the 1, 2 or 3 position of the triazole ring and is hydrogen, C1-10 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl C1-4 alkyl, phenyl, benzyl or acyl. These compounds are pharmaceutically active and are especially useful in the treatment of disorders of the central nervous system. They are prepared by reacting an amine of formula RSH with a triazolobenzodiazepine intermediate appropriately substituted at the 10-position or by ring-closing the appropriate anilinotriazole.
    公开号:SU1169538A3
    申请号:SU823519543
    申请日:1982-12-06
    公开日:1985-07-23
    发明作者:Кумар Чакрабарти Джибан；Майкл Хоттен Терренс；Джеймс Стегглз Дэвид
    申请人:Лилли Индастриз Лимитед (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to organic chemistry, in particular to methods for producing new tricyclic compounds exhibiting psychotropic activity. A known method for producing tricyclic compounds of general formula Kg (L x YoVR -N of which the closest in terms of site and biological activity is the compound, RF, Rj-Rj CHg. The purpose of the invention is a method for producing new tricyclic compounds. Example 1. 4- (4- 1 tor-2-nit phenylamino) -2-methyl-1,2, 3-triazole-carboxylic acid. 4- (4-Fluoro-2-nitrophensh1amino) -2-methyl-1, 2 , 3, -triazole-3-carbonipip (0.5 g) is dissolved in a mixture of ethanol (10 ml) and 2.5N aqueous solution of potassium (20 ml) and heated at reflux overnight. 100 ml of water and filtered. The filtrate is acidified (3 MP HC1 conc.) and extracted twice with chloroform (2 x 50 ml). The organic extract is washed with water, evaporated over magnesium sulfate, evaporated under reduced pressure and a semi-orange solid is obtained. a substance whose recrystallization from ethanol is obtained from ethanol is O, 5 g of an orange crystalline solid (EtOH), mp 250 ° C. Example 2. Methyl 4- (4-fluoro -2-nitrophenylamino) -2-methyl-1, 2,3.-Triazolyl-5-uvrboxylate. This acid (0.3 g) was dissolved in methanol (20 ml) with then concentrated sulfuric acid (O, 5 ml) was added dropwise and the solution was heated at reflux temperature overnight. The cooled solution is neutralized with sodium bicarb (2 g), filtered, the filtrate is evaporated to dryness under reduced pressure and a yellow solid is obtained, which is extracted with chloroform, the filtrate is evaporated and evaporated to give 0.3 g of an orange / t.et. 208.5-210.5С. Example 3. 7-Fluoro-2-methyl-10- (4-methyl-1-piperazinyl) -4H-1,2,3 triazole - (4,5-b) - (1,5) -benzodiazepine. . This nitro ester (0.23 g) was dissolved in absolute ethanol (50 ml) and a suspension of palladium on charcoal (10%, 0.2 g) in ethanol (20 ml) was added to the solution. The solution is subjected to hydrogenation in a Parr apparatus at a pressure of 60 pounds per square inch at room temperature for 60 minutes. The solution is filtered through a celite pad, evaporated to dryness under reduced pressure, and 200 mg of a white solid are obtained, methyl 4- (4-fluoro-2-aminophenylamino) -2-methyl-1,2,3-triazole-3-k arbokshtat . The white amino ester, N-methylpiperazine (0.5 ml) and amisole (10 mp) are placed in a three eagle flask equipped with a thermometer, a dropper and a stirrer, and stirred under nitrogen at an ice-water bath at 0 ° C. In solution a solution of titanium tetrachloride (0.5 ml) in anisole (10 ml) is added. After that, the stirred mixture is heated and maintained at 90 ° C overnight. The product is 4- (4-fluoro-2-aminophenylamino) -1,2,3-triazole-5- (4-metsh1-1-piperazinyl) -carboxamide with m.p. 148-149 ° C. MS: M 333; IR.carbonyl, 1590 cm-, NH 3250-3400 cm-. 70 mg of this product is subjected to additional heating at 150 s for 72 h. The cooled reaction mixture is poured into a mixture of water in ammonia and ethyl acetate (50:10:20 ml) and filtered through a celite pad. The organic phase is separated, washed twice with water, dried over MgSQ, filtered and evaporated to dryness under reduced pressure. The resulting material is chromatographed on a magnesium silicate column, eluting with a mixture of methanol and chloroform (5:95). The desired fraction is evaporated under reduced pressure and get 0.03 g of yellow
    3 t1695384
    crystalline solid matter C H-.FN
    (ethyl acetate-hexane), 7-ftsr-2-Calculated, Z: C 57.13; H 5.75;
    -methyl-10- (4-metsh1-1-piperazinyl) -N 31.09; F 6.03.
    -4H-1,2,3-triazole- (4,5-b) - (1,5) -MS: M 315; H NMR (60 N) TMS
    - benzodiazepine, t. pl. 193-195®С.s0.00, solvent SECOND: 2.32
    Elementalysis, {S, ЗН); 2.45 (t, 4H); 3.77 (t, 4H);
    Found,%: C 56.98; H 5.52; 4.02 (S, 3N); 5.42 (s, 1H); 6.85-8.4
    N 30.89; F. 6.28. (T, 3N).
    权利要求:
    Claims (1)
    [1]
    METHOD FOR PRODUCING TRICYCLIC COMPOUNDS of general formula “2
    ABOUT
    Sr n
    where R 7 is halogen;
    Rj is methyl;
    Rj is methyl, characterized in that. a compound of the formula where 1C- have the reaction, the indicated closures are ring-exposed even at 150 ° C in an organic solvent such as anisole.
    SU, „, 1169538
    1 1169538. . 2
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    CH468400A|1965-12-23|1969-02-15|Sandoz Ag|Process for the preparation of new thieno benzothiazepin-4-one compounds|
    US3450694A|1966-02-23|1969-06-17|Abbott Lab|Substituted benzoxazepines and benzothiazepines|
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    US3758479A|1967-03-22|1973-09-11|Sandoz Ag|Nitro and sulphamoyl substituted dibenzodiazepines|
    CH491956A|1967-11-30|1970-06-15|Geigy Ag J R|Process for the preparation of new thiazepine derivatives|
    US3987052A|1969-03-17|1976-10-19|The Upjohn Company|6-Phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines|
    CA918659A|1969-07-31|1973-01-09|Yoshitomi Pharmaceutical Industries|11--dibenzo thiazepines|
    GB1292410A|1970-05-13|1972-10-11|Yoshitomi Pharmaceutical|Thienobenzothiazepine derivatives|
    BE791902A|1971-11-26|1973-05-24|Wander Ag Dr A|NEW DERIVATIVES OF THIENO BENZAZEPINE, THEIR PREPARATION AND THEIR APPLICATION AS MEDICINAL PRODUCTS|
    US3962248A|1972-04-04|1976-06-08|Sandoz, Inc.|Process for making 11-piperazino-diazepines, oxazepines, thiazepines and azepines|
    NL7403657A|1973-03-23|1974-09-25|
    US4172831A|1974-11-26|1979-10-30|Lilly Industries Limited|Thieno-benzodiazepines|
    US4115568A|1974-11-26|1978-09-19|Lilly Industries Limited|Thieno[3,2-b]-[1,5]benzodiazepines|
    US3951981A|1975-02-24|1976-04-20|American Cyanamid Company|Substituted benzodiazepines and method of use|
    US3953430A|1975-02-24|1976-04-27|American Cyanamid Company|Substituted benzodiazepin-10-ones and method of use|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    GB8039659|1980-12-11|
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