• 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:
    7β-Acylamino-3-trifluoromethylsulfonyloxy-1-carba-3-cephem-4-carboxylic acid antibitic compounds, esters and salts thereof, and the corresponding 7-amino and protected 7-amino 1-carbacephalosporins are provided. The 3-trifluoromethylsulfonyloxy-substituted 1-carbacephalosporins also are useful in a process for preparing 3-halo-1-carbacephalosporins which comprises displacing the 3-trifluoromethylsulfonyloxy ester group with halide ion in an aprotic polar solvent.
    公开号:SU1547709A3
    申请号:SU864027886
    申请日:1986-07-15
    公开日:1990-02-28
    发明作者:Альберт Эванс Дэвид；Брайан Съерген Эрик
    申请人:Президент Энд Феллоуз Оф Гарвард Колледж (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to the production of new derivatives of Cephem-carboxylic acids, namely 7-substituted 3-galot1 -carb (child) -3-Cephem-4-carboxylic acid of the general formula>
    n and
    where th 1 is C, -C 4 ~ alkoxy or a group of the formula ba (child) -Z-cephem-4-carboxylic acid of the general formula I
    And n I ^ oin-g — o U—
    I COOR2 where R f is C ^ -C ^ alkoxy or phenoxy / R_ T -H or a carboxy-protecting group (η. Nitrobenzyl); HA1-C1 with or W, which are intermediates Z-halo-1-karbatsefalosporinovyh antibiotics. The goal is to develop a method for producing new intermediate compounds. The preparation is carried out by reacting the compound f-I, where Hal OSO ^ CFs, with lithium chloride or bromide in an aprotic polar solvent, followed by, if necessary, removal of the carboxy-protecting group.
    0-o-cn g B 2 is hydrogen or a carboxy-protecting group such as η is nitrobenzene;
    Hal - chlorine or bromine, which are intermediates of 3-halo-1-carbacephalosporin antibiotics.
    The purpose of the invention is the development on the basis of well-known methods of a method for producing new intermediate products, allowing to obtain a chemically more stable carbocephalosporin antibiotic.
    Example 1 7 / z- (P-phenylglycylamido) -2-trifluoromethylsulfonyloxy-1-carba-3-cephem-4-carboxylic acid.
    Complex benzyl ether. 7 p- [G-2- (t-butyloxycarbonylamino-2-phenyl) -acetamido 7 ~ 3-hydroxy-1-carba-3-cephem-1-carboxylic acid are reacted with trifluorobtansulfonic anhydride in the presence of triethylamine, to obtain a T-BOC-protected complex 3-trifluoromethylsulfonyl-hydroxyether. The t-butyloxycarbonyl protective group f5 was removed with τ-toluenesulfonic acid, and the benzyl ester was removed with aluminum chloride and anisole to give the title compound. · 20
    Example 2. p-Nitrobenzyl-7 / - phenoxyacetylamino-3-chloro-1-carba ’(child) -3-cefem-4-carboxylate. .
    A solution of 240 mg of p ~ nitrobenzyl-7d-phenyloxy-ethylamino-3-trifluoromethyl-25. Sulfonyloxy-1-carba (child) -3-cefem-4-carboxylate and 500 mg of lithium chloride in 3 ml of DMF was heated at 80 ^ 0 in for 5.5 hours. The reaction mixture was then cooled, diluted with ethyl acetate, jq
    - washed with water and brine, dried over magnesium sulfate and concentrated by evaporation. The concentrate was chromatographed on silica gel and the product was eluted with methylene chloride-35 ethyl acetate. Evaporation of the eluate gave 112 mg of the title compound as a yellow foam. The product was then further purified by chromatography over silica gel. . _ 40
    Example 3. 7β-phenoxyacetyl- 1 amino-3-chloro-1-carbo (child) -3-cefem-4-carboxylic acid.
    Benzyl 7 / z-phenoxyacetylamino-3-trifluoromethylsulfonyloxy-1-carbo- (de-45thia) -Z-cefem-4-carboxylate was heated at 80 ° C in DMF with excess lithium chloride to obtain the corresponding complex 3-chloro- 3-cefembenzyl ether. The benzyl ester group was removed with aluminum trichloride and anisole to give the title compound.
    Example 4. t-6yTHn-3 / j-t-6ythyloxycarbonylamino-3-chloro-1-carbo (child) -3-cefem-4-carboxylate.
    A solution of 250 mg (0.51 mmol). t * -6ythyl-3 ^ -t-butyloxycarbonyl-amino-3-trifluoromethylsulfonyloxy.i-1-carba (child) -3-cefem-4-carboxylate and 1.6 g of dry lithium chloride in 10 ml of dry dimethylformamide were heated in atmosphere | argon sphere for 8 hours at 8090 ° C. Then the reaction mixture was poured into a mixture of 150 ml of water and 150 ml of ethyl acetate. The organic layer containing this product was separated and then washed twice with 25 ml of part-. mi 0.1 n HCl with brine and dried over sodium sulfate. After removal of the drying aid by filtration, the dried and washed reaction mixture was chromatographed over 25 g of silica using 5% ethyl acetate / methylene chloride. 20 mg (10% yield) of the title compound were obtained having the following physical characteristics:
    NMR (90 MHz): 1.42, (s, 9H)
    1.52 (s, 9H); 1.78 (m, W) { 2.08 (m, 1H); 2.62 (AB, J = 4, 2H); 4.79 (dt, J = 11.4, 1H); 5.13 (m, 2H).
    Mass spectrum 372 M, 374 M + + 2.
    权利要求:
    Claims (1)
    [1]
    Claim
    The method of obtaining 7-substituted 3-halo-1-carba (detia) -Z-cephem-4-carboxylic acid of the general formula n θΛcoor 2 where R t - C, -C. 4 ~ alkoxy or gr'appa formula. .
    O-0-cn 2 R ^ - hydrogen or a carboxy-protecting group such as p-nitrobenzyl /
    Hal - chlorine or bromine, characterized in that the compound of General formula n and
    RiCONH ^ - / oso 2 cf 2 COOR 3 treated chloride or lithium bromide in an aprotic polar solvent, followed by, if necessary, t, removing the carboxy-protecting group.
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    同族专利:
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    AT52779T|1990-06-15|
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US4226866A|1972-11-06|1980-10-07|Merck & Co., Inc.|Novel antibiotic analogues of cephalosporins|
    US3925372A|1973-02-23|1975-12-09|Lilly Co Eli|Alpha-aminoacyl-3-halo cephalosporins|
    US4275207A|1978-08-14|1981-06-23|Merck & Co., Inc.|Process for preparing 7--3--1-carbadethiaceph-3-em-3-carboxylic acid and intermediate therefor|
    JPS6058920B2|1978-12-26|1985-12-23|Kyowa Hakko Kogyo Kk|
    NO155548C|1979-02-10|1987-04-15|Kyowa Hakko Kogyo Kk|PROCEDURE FOR THE PREPARATION OF OPTICALLY ACTIVE CEPHALOSPORIN ANALOGS.|
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    US5019571A|1988-01-25|1991-05-28|Eli Lilly And Company|1-carbacephalosporin antibiotics|
    US4855418A|1988-03-23|1989-08-08|Eli Lilly And Company|Process for production of ceophalosporins|
    US4820832A|1988-03-23|1989-04-11|Eli Lilly And Company|Process for preparing 3-unsubstituted cephalosporins and 1-carbacephalosporins|
    US4895940A|1988-10-19|1990-01-23|Pfizer Inc.|Process for the preparation of penems|
    US5191075A|1988-10-19|1993-03-02|Pfizer Inc|Process for the preparation of penems|
    US4992543A|1988-10-19|1991-02-12|Pfizer Inc.|Penem derivatives|
    US5159073A|1990-09-13|1992-10-27|Eli Lilly And Company|Intermediates to 1-carbacephalosporins and process for preparation thereof|
    US5225553A|1990-09-13|1993-07-06|Eli Lilly And Company|Intermediates to 1-carbacephalosporins and process for preparation thereof|
    US5206360A|1990-10-22|1993-04-27|Bristol-Myers Squibb Company|Intermediates for cyclobutenedione substituted cephalosporin compounds|
    US5106842A|1990-10-22|1992-04-21|Bristol-Myers Squibb Co.|Antibiotic c-3 cyclobutenedione substituted cephalosporin compounds, compositions, and methods of use thereof|
    US5169843A|1990-10-22|1992-12-08|Bristol-Myers Squibb Company|Antibiotic C-3 cyclobutenedione substitutedcephalosporin compounds, cmpositions, and methods of use thereof|
    US5099015A|1991-01-10|1992-03-24|Eli Lilly And Company|Trifluoromethyl 1-carbacephems|
    US5084447A|1991-04-25|1992-01-28|Eli Lilly And Company|C-3 phosphine oxide substituted carbacephalosporins|
    CA2246753C|1996-02-23|2005-05-10|Robert Frederick Bruns Jr.|Non-peptidyl vasopressin v1a antagonists|
    CN107556212B|2017-09-14|2020-03-24|台州昌霖化工科技有限公司|Method for preparing 2-diazo-acetoacetic acid p-nitrobenzyl ester|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US06/761,647|US4673737A|1985-08-02|1985-08-02|7-acylamino--3-trifluoromethylsulfonyloxy-1-carba-3-cephem-4-carboxylic acids and esters thereof|
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