• 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:
    Process for production of 3,4-dihydro-2-methyl-4-oxo-2H-1,2-benzothiazine-3-carboxylic acid-1,1-dioxide by hydrolysis, in the presence of hydroxide ions, of an alkyl or aralkyl ester thereof followed by precipitation of the acid at pH below 6.0 and its use as an intermediate for the production of N-(2-pyridyl)-3,4-dihydro-2-methyl-4-oxo-2H-1,2-benzothiazine-3-carbox amide-1,1-dioxide and the analogous N-(2-thiazolyl)-compound, effective antiinflammatory agents.
    公开号:SU833159A3
    申请号:SU782607699
    申请日:1978-04-27
    公开日:1981-05-23
    发明作者:Дитрих Хаммен Филип
    申请人:Пфайзер Инк. (Фирма)；
    IPC主号:
    专利说明:

    where Z is an OH group or a halogen atom, and the process is carried out in the presence of at least an equivalent amount of a dehydrating binding agent, if a compound of formula (II) is used, where Z is an OB group, the compound is preferably used ( Ii) where Z is a chlorine atom. The process is carried out in the presence of an acid acceptor, in which 2-aminopyridine is used.
    N-ethoxycaronyl-2-etoxy-1, 2-dihydroquinoline, N, N -carbonyldiimidazole, NN -dicyclohexylcarbodiimide, N., N-carbonyl-5-triazine, ethoxyacetylene, N-o-oxo-acetylene, N-o-oxyxylate, N-hydroxymethyl, o-oxyxycarbodiimide, N., N. oxysuccinimide, N-hydroxypiperidine or diphenyl ketone-p-tolylamine.
    A distinctive feature of the process is the use of 1,2-dioxide-3, 4-dihydro-2-methyl-4-oxo-2H-1,2-benzothiazine-3-carboxylic acid, yl as an acylating agent. its acid halide.
    Example 1. Preparation of 1,1-dioxide .N- (2-pyridyl) -3,4-digidro-2-methyl-4-oxo-2H-1, 2-benzothiazine-3-carboxamide.
    A 25 ml three-necked round-bottomed flask, equipped with a magnetic stirrer, a backflow cage and glass stoppers, was charged with 1.82 ml of thionyl chloride, 12.8 ml of iso-propyl ether and 1.28 g of 1,2-dioxide-3, 4- dihydro-2-methyl-4-oxo-2H-1, 2-benzothiazine-3-carboxylic acid. The mixture is heated at reflux temperature and stirring for 5 hours; then evaporated under reduced pressure. The residue is washed with 10 ml of M, K-dimethylformamide and the resulting solution is used directly in the next stage.
    To the resulting solution of acid chloride in N, N-dimethyl forms and added with stirring 1.03 g of 2-aminopyridine. An exothermic reaction begins with the formation of a red color, which changes to orange-yellow for .5 min. The reaction mixture is stirred overnight, then it is diluted slowly with the addition of 40 ml of water. The precipitated precipitate is granulated for half an hour, then filtered, washed with water and dried in air (1.3 g, 79%). Mp, 16O-175 ° C. The precipitate is purified by dissolving in N, N-dimethylacetamide (1 ml per OD g) at 50-60 0 and precipitated from it by adding 5-fold volume of methanol and cooling. The yield of pure product is 30%, m.p. 198-200 C. The identity of the compound is confirmed by infrared and mass spectrometry.
    This result is obtained by replacing thionyl chloride with thionyl bromide.
    Example 2. Obtaining 1,1-dioxide M- (2-thiazolyl) -3,4-dihydro-2-methyl-4-oxo-2H-1, 2-benzothiazine-3-carboxamide.
    The procedure of Example 1 is repeated, but 510 mg 1,1-dioxide 3,4 is used to prepare 1,1-dioxide 3 f4-dihydro-2-methyl-4-oxo-2H1, 2-benzothiazine-3-carboxylic acid chloride. -dihydro-2-methyl-4-oxo-2H-1, 2-benzothiazine-3-carboxylic acid, 1.45 MP of thionyl chloride, 10.0 ml of isopropyl ether and 2 ml of N, N-dimethylformamide. Then the acid chloride reacts. with 400 mg of 2-aminothiazole by the acylation procedure of Example 4 and 532 mg of product are obtained (79% crude),
    The product is purified by dissolving in .3 ml of N, N-dimethylformamide at b, filtering the solution, followed by diluting the filtrate with 15 ml of methanol. Yield 208 mg (33%), T.Sh1. .234240 ° C. A repetition of such a process gives a clean product. The identity of the product is confirmed by infrared and mass spectrography.
    Example 3: Preparation of N- (2-pyridyl) -3,4-di-Hydro-2-methyl-4-oxo-2H-1, 2-benzothiazine-3-carboxamide 1,1-dioxide.
    To a solution of 127 mg, 1,1-bccyig3, 4-dihydro-2-methyl-4-oxo-2H-1,2-benzothiazine-3-carboxylic acid and 52 mg of 2-aminopyridine in 5 mp of tetrahydrofuran is added with stirring 148 mg of N-ethoxycarbonyl-2-ethoxy-1, 2-dihydroquinoline in 1 ml of tetrahydrofuran. The mixture is stirred at a temperature of 23-25 seconds for 4. h, then evaporated under reduced pressure to an oil. Thin-layer chromatography on silica gel plates in the benzene-acetic acid system (95: 5) and the illumination of the plates with a lamp with a wavelength of 366 micron, shows the presence of this compound compared to an identical sample. .
    When repeating this technique, but used instead of N-ethoxy-carbonyl-3-ethoxy-1, 2-dihydroquinoline, N, N-dicyclohexylcarbodiimide, N, N carbonyl-5-triazine, N, N -carbonyldiimidazole, ethoxyacetylene, diphenyl ketene, -tolylamine, N-hydroxysuccinimide, N-hydroxyphthalimide or N-hydroxypiperidine as combining reagents, get the same result.
    权利要求:
    Claims (3)
    [1]
    Invention Formula
    A process for the preparation of N- (2-pyridyl or 2-thiazolyl) -3,4-digidro-2-methyl-4-oxo-2H-1, 2-benzoti and ein-3-car-6-amamide amide 1,1-dioxide. .- where R is 2-pyridyl or 2-thiazalyl, by the interaction of the formula where RQ. with the acylating agent, distinguished by the fact that, in order to simplify the process, a compound of the formulas is used as an acylating agent, where Z is an OH group or a halogen atom, and the process is carried out in the presence of at least measure an equivalent amount of a dehydrating binding agent if a compound of formula (II) is used, where 2 is an OH group. 2. Method POP.1, from. This is because a compound of the formula (p.) is used as the acylating agent, where Z is a chlorine atom. 3. The method according to claims 1-2, that is, that the process is carried out in the presence of an acid acceptor. 4. The method according to claims 1 to 3, about tl and h ay u and with the fact that 2-aminopyridine is used as an acceptor of acids. 5. The method according to claim 1, about tl and h and yushchi and with the fact that as the dihydrating binding agent use M-toxoxycarbonyl-2-ethoxy-1, 2-dihydroquinoline, N, N -carbonyldiimidazole, j N , N -dicyclic exilcarbodiimide, N, N -carbonyl-5-triazine, ethoxyacetylene, N-hydroxyphthalimide, N-OK succinimide, N-hydroxypiperidine, or / diphenyl ketene-p-tolylamine. Sources of information taken into account in the examination 1.Patent: ailA 3927002, cl. 260-294.8, publ. 1975.
    [2]
    2. US patent number 3891637, cl. 260-243, pub. 1975.
    [3]
    3. The US patent 3591584, cl. 260-243, pub. 1971 (prototype).
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    同族专利:
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US3501466A|1967-11-30|1970-03-17|Mcneilab Inc|3-carbamoyl and 3-alkoxycarbonyl benzothiazine-1,1-dioxides|
    US3492298A|1968-02-21|1970-01-27|Mcneilab Inc|Oxazino-benzothiazine-6,6-dioxides|
    US3591584A|1968-08-27|1971-07-06|Pfizer|Benzothiazine dioxides|
    US3808205A|1971-09-10|1974-04-30|Warner Lambert Co|Process for the preparation of 4-hydroxy-3-carbamyl-2h-1,2-benzothiazine 1,1-dioxides and 4-hydroxy-3-1,2-benzothiazine carboxylate-1,1-dioxides|
    US3853862A|1973-04-23|1974-12-10|Pfizer|Production of 4-hydroxy-1,2-benzothiazine-3-carboxamides|
    US3892740A|1974-10-15|1975-07-01|Pfizer|Process for the production of carboxamides of oxo-1,2-benzothiazine-1,1-dioxides|
    US3991584A|1975-01-31|1976-11-16|Western Gear Corporation|Shock absorbing and retracting system for pipe laying vessel|
    US3960856A|1975-06-20|1976-06-01|Warner-Lambert Company|Process for the preparation of 4-hydroxy-3--2-methyl-2H-1,2-benzothiazine 1,1-dioxide|DE2756113A1|1977-12-16|1979-06-21|Thomae Gmbh Dr K|NEW 4-HYDROXY-2H-1,2-BENZOTHIAZINE-3-CARBOXAMIDE-1,1-DIOXIDES, THE PROCESS FOR THEIR MANUFACTURING AND THE MEDICINAL PRODUCTS CONTAINING THESE|
    US4434164A|1981-06-01|1984-02-28|Pfizer Inc.|Crystalline benzothiazine dioxide salts|
    US4474955A|1981-06-17|1984-10-02|Vincenzo Iannella|Process for preparing 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-[N-carboxamide]-1,1-dioxide, and its phosphoric ester|
    IN159273B|1981-10-05|1987-04-25|Pfizer|
    EP0098422B1|1982-07-07|1987-12-09|Siegfried Aktiengesellschaft|Process for preparing 4-hydroxy-2-methyl-n-2-pyridyl-2h-1,2-benzothiazine-3-carboxamide 1,1-dioxide|
    DE3311165A1|1983-03-26|1984-09-27|Gödecke AG, 1000 Berlin|FINE CRYSTALLINE ISOXICAM|
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    WO1997046532A1|1996-06-03|1997-12-11|Boehringer Ingelheim Pharmaceuticals, Inc.|2-benzyl-4-sulfonyl-4h-isoquinolin-1,3-diones and their use as anti-inflammatory agents|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US05/694,572|US4100347A|1976-06-10|1976-06-10|3,4-Dihydro-2-methyl-4-oxo-2H-1,2-benzothiazine-3-carboxylic acid-1,1-dioxide|
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