• 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:
    7-Acylamido-3-hydroxy-3-cephem-4-carboxylic acid ester sulfoxides are chlorinated and reduced in a single step process with phosphorus trichloride in dimethylformamide to provide 7-acylamido-3-chloro-3-cephem-4-carboxylic acid ester sulfides.
    公开号:SU1018586A3
    申请号:SU772511154
    申请日:1977-08-15
    公开日:1983-05-15
    发明作者:Куколя Степан；Овербаф Спрай Дуглас
    申请人:Эли Лилли Энд Компани (Фирма)；
    IPC主号:
    专利说明:

    HsoiSpede is a process for the preparation of 3 chlorocephemo8 of formula (1) Rj S. O b COOCH2 where R is phenylacetyl or phenoxyacetyl,. . , R2 is a hydrogen atom, or R and R, together with the nitrogen atom to which they are bonded, form a phthalimido radical, which have pharmaceutical activity and are highly effective in treating and preventing bacterial infections. A method is known for producing 3-chloro cephemes described by the formula (HB by chlorination of the corresponding 3-ox chpheme with phosphorus trichloride in the presence of (dimethylformamide in anhydrous conditions at shielding or at room temperature) Cll The disadvantage of this method is the lack of None of the 3-hydroxephemers are prepared. Dissimilar Z-oxinephemes are obtained, based on the available compounds, penicylLinrv in three hundredfold methods: first, penicillin sulfoxide is rearranged to obtain 3% methylene cepham, 2%, then 3- ethyl, cefam, the sample and the sample, the sample and the sample, the sample and the sample, the sample and the sample, the sample and the sample, the sample and the sample, the sample and the sample, the sample and the sample and the sample, the sample and the sample, the sample and the sample, the sample and the sample, the sample and the sample, the sample and the sample, the temper sample; The fercid is reduced to 3-ox "cephea. The aim of the invention is to simplify the process technology. The goal is achieved: by the method of obtaining the 3-h orb-formula (11, which is; that the compound is ft ft I --s where R and have the indicated values are subjected to halogenation by treating with trichloro phosphorus or phosgene in the presence of dimethylforma62 under anhydrous conditions with cooling or at room temperature. Advantageously, the process is carried out at a temperature of from -65 ° C to room temperature, preferably ° at room temperature. . . The halogenation of compounds of formula (I) is carried out predominantly with phosphorus trichloride. It is used in an amount of 2 to 9 mol and most preferably 3 mol, per 1 mol of the compound of formula (P). CoGde in the compound of the formula (P) R is phenoxycetyl and kn is a hydrogen atom. Halogenation is favorably carried out with phosgene, in this case the process is preferably carried out using 2 to 9 mol of phosgene per 1 mole of the compound of formula (Q) and at a temperature of -60 -. A distinctive feature of the process is that a compound of the formula (0), pre-., Is used as the starting 3-oxycephemic compound. sulfoxide; and, halogenation is carried out along with phosphorus trichloride and phosgene. In this way, the reduction and chlorination of the starting product is carried out simultaneously in one stage. When carrying out the process according to the invention, the 3-hydroxy-3-cep Sulfoxide ester of formula (P) is added to a solution of a halogenating reagent in de (dmf) dimethyl forms. The solution is cooled to a temperature of the order of and -60 ° C, it is more preferable to cool the solution to -50 -55 ° C directly before adding the sulfoxide. The reactive mixture is agitated, for example, by stirring or mixing, and the temperature of the mixture increases at the time of addition of the sulfoxide. After the addition is complete, the reaction mixture is brought to ambient temperature and then further mixed for T-2 hours. The reaction can be carried out by adding the halogenating reagent B to a cooled solution of sulfoxide in DMF. However, it is preferable to add the sulfoxide to the dMHP reagent in the manner described. For best results, DMF is dried on molecular ity. The ratio of t-halogenating reagent to the ester of Z-cephemsulfoxide. 2: 1 is planted in low yield. Higher proportions of reagent, e.g. 9 18 MOJib and more, may be used, however, such excess amounts are not necessary. The best solution of the reagent in 7} MF is prepared at a temperature below -10 ° C. Preparation of the solution is accompanied by an increase in temperature, as a result of which it is necessary to provide for the solution to be smoothed so that the temperature does not rise above I 0 ° C. The solution of the reagent is prepared in .DMF, prepared at higher temperatures, entail a decrease in the yield of the ether Z-chloro-Zze-, fema. The starting 3-hydroxy-3-cefemsulum ampicides of formula (ft) (1-oxides |, are more stable in storage than the corresponding Zonsi-3 cephemes and, in ocriCfBHOM, more crystalline ... .. Appro. 1. 4 -Nitrobenzyl 7 phenoxyacetamido-3 chloro-3 cephem-A-carboxylate. 620 ml of the cooled to - dimethylphenoamamide 1.31 ml (d 1.57) of trichlorosystrophonosfry is added while the mixture is stirred, the solution is mixed; , and bhla adat with cyxoroi ice and acetone. The cold solution is diluted with the cooled races; ovine in the amount of 2.51 g (5 mol) or trvbenzyl-7-phen6-xiace gamidr 5 hydroxy-3-cephem-1-carboxylate) oxide in if About ml of DMF. After the addition, the leya is mixed in an ice bath c. when used for 4aGja and at room feMnepaType for one esate hour. Reacting mixture: b is separated with ethyl acetate: and QKCTpat T is washed twice with a dilute sodium bicarbonate solution and twice with distilled water, leaving it dry. The extract is evaporated under vacuum. The resulting substance is purified by chromatography per to g of silica gel using 600 mp of toduol and 600 ml of 1: 1 ethyl acetate: toluene, volume: volume: The yield of purified substances of substance, 9b7 g (38.5% yield). md in CDCJv slz, 5, 3.80 (AB, J 18 Hz, 2jH r, 4.55 is, 2, phenoxy methyl), 5, OZG d, J 5H2, l, Hfe). . 5.35 (S, 2, U-nitrobeneyl), 5.88 (J 5.10 Hz, 1, H2). 1 86 L p and M e p 2., 4-nitrrbenzyl 7 Phenoxy acetamido-3 chloro-3-cephem-carboxylate. To a cold (-55 ° C) DMF 6 solution: the amount of 30 ml (the reagent is sorted and dried on a molecular sieve) is added 2.05 ml of phosphorus trichloride. L-mg (8 mmol) of solid -nitrobenzyl 7 Phenoxyace- is introduced into this cold solution with g | tamido-3-hydroxy-3-cephem- -carb.oxylate sulfoxide. After tO mime after the addition of laziness, the temperature: the reaction mixture rises to. At this temperature, the mixture is stirred for 90 minutes. The substance is released as follows. Add 30 ml of hydrochloric methylene together with 60 g of ice and to the mixture. 35 ml of water. After agitating the mixture, the methylene chloride extract, - is extracted, which is subjected to five-fold washing with portions of cold water, each in 45 ml each, containing 0.6 g of sodium chloride, and then dried with magnesium sulfate. As a result, C-nitrobenzyl is obtained. 7 phenoxyacetamido-3 chloro-3-cephem-carboxy lat, which is analytically identical to the substance obtained in Example 1. The yield is evaluated by N-deacylation of the substance to obtain 7 amino compounds as follows. . Take the extract containing the substance in the amount of 38 ml with methylene chloride. The solution is cooled to -1 and treated with shredded with 0.9 ml of pyridine and 2.08 g of phosphorus chloride. The mixture is stirred for one hour at 20-25 0, cooled to, after which it contains d6ba8l gog, 6 ml of isobutanol. The mixture is then stirred for 3 hours at room temperature, and the solution of 4-nitrobenzyl 7 amino-3 chloro-3-cephem-4-carboxylate will stop clear. After that, the substance is filtered off and washed with methylene chloride. The substance is dried to bc 2.03 g (62.6 yield). EXAMPLE 3 7. -nitrobenzyl 7 Phenoxyacetamido-3 chloro-3-cephem-i-karboxylate t. The synthesis processes in these examples were carried out under conditions similar to those described in example 2, except that the amount of phosphorus trichloride was 5 It is 2.72 ml and the initial temperature at which the addition of ether sulfoxide is different. In each example, the substance is analytically identical to the substance that is given in Example 1. The amounts obtained, as in Example 2, are evaluated by deacylation of the substance to obtain the 7-amino-cyclic compound. The table below shows the true temperature at which the sulfoxide is added to the reaction mixture, and the amount of the 7-amino-cyclic compound obtained PRI me R 8. L-nitrobenzyl 7-phenoxyacetamido-3-chloro-3-cephem-k-CZ rbo xi l at. The process is carried out similarly to the process in Examples 3- / except that the initial mixture consists of ether sulfoxide dissolved in DMF and the last one is added trichloride phosphorus, when the temperature of the mixture being processed is set to low. The substance, namely, nitrobenzyl 7-phenoxyacetate chido-3-chloro-3-cephem-A-carboxylate, is analytically analogous to the substance from example 1. The yield is again evaluated by the hyTe of a 7-aminocyclic compound, which is obtained in an amount of 1.73 g (53.5). PRI me R 9. -nitrobenzyl 7-fanoxiacetamido-3-chloro-3-cephem carboxylate. The same process for the preparation of the substance is used as in Examples 3-7, except that the sulfoxide ether is slowly added over 866.2 minutes at a reaction temperature of -30 ° C. Substance, namely "-nitrobenzide 7-phenoxyacetamido-3-. -chloro-3-cephem-4-carboxylate, still oasis evaluated with the help of deacylation. The yield of the 7-aminocyclic compound is 1.83 g (5b, 6%), and the substance obtained is analytically identical to the substance of Example 1. EXAMPLE 10. -nitrobenzyl 7-phenoxyacetamido-3-chloro-3-cephem-1-Ka rboxylate. 1.75 ml of phosphorus trichloride is added at -20 ° C to 100 ml of DMF. After that, the mixture is stirred and heated to room temperature. The mixture is then cooled to dropwise and 5.01 g of plant, thief, 4-nitrobenzyl, 7-phenoxyacetamido-3-hydroxy-3 cephem carboxylate sulfoxide, diluted in 60 ml of DMF is added dropwise. The mixture is stirred for one hour, after which the cooling, the bath is removed and the mixture is heated to ambient temperature, then stirred again for one hour. After that, the mixture is processed. in the same way as in Example G, in order to obtain 0.95 g of L-nitrobenzyl Y-phenoxyacetamido-3-hlrr-3-cephem-h-carboxylate, which is analytically identical to the substance obtained in Example 1, at a yield of 18.9 . For example 11. -nitrobenzyl 7-phenoxyacetamido-3-op-3 cefem-4-carboxylate. 0.87 ml of phosphorus trichloride is mixed with 5 ml of DMF and stirred for five minutes. Then, 1 g of a solution of α-nitrobenzyl 7-phenoxyacetamido-3-hydroxy-3-cephem-4-carboxylate sulfo- is added dropwise to the solution. sid dissolved in 20 ml of DMF with simultaneous stirring. After the addition is complete, the reaction mixture is heated to r7 ° C and stirred at this temperature for one hour. After that, the mixture is heated to ambient temperature and stirred for one more hour. When the substance is isolated as in example 1, O g of i-nitrobenzyl 7 phenoxyacetamido-3-chloro-3-cephem-carboxylate is obtained, which is analytically identical to the substance from example 1, with a yield of 43.3%. PRI me R 12. 4-nitrobenzyl 7-phenoxyacetamido-3-chloro-3-cephem- - carboxylate.
    In a 0.25 g solution of -nitrobenzyl 7 phenoxyacetamido-3 6xy-3-efem-carboxylate sulfoxide in 18 ml of DMF at -50 ° C, a mixture of 0.26 ml of phosphorus trichloride and 2 ml of DIF is added. Immediately after the end of this addition, the reaction mixture is heated to ambient temperature and stirred for one hour. After that, the mixture is treated in the same manner as in Example 1 to obtain 0.12 g of 4-nitrobenzyl 7 Phenoxyacetamido-3. Chloro-3 cephem-4 carboxyl: aha, which is analytically identical to the substance obtained Example b Output A9% of terretichesgr.
    EXAMPLE 13 0.1 g of 4-nitrRbenzyl 7 phenoxyacetamido-3 hydroxy-3-cephem-carboxylate sulfoxide is dissolved in 6 ml DMF at a temperature of ambient air and 0.05 ml of phosphorus trichloride is added. The mixture is stirred at an ambient temperature for one hour; the substance is then isolated according to the scheme of Example I in order to obtain 0.02 0.028 G -nitrobenzyl 7 Phenoxyacetate mydo. -3-U1br-3-CepaM-carboxypate, which is analytically identical to the substance from Example J. Exit 28 from theoretical.
    Pr 1.4. t-nitrobenzyl 7 Phenoxyacetamide (I-3-chloro-3-aephem-f-catebrate,.
    At an ambient temperature of 0.83 g of nitrobenzyl 7-phenoxyacetamido-3-hydroxy-3-cephem carboxylate sulfoxide in 25 ml of DNF, 0.17 ml of phosphorus trichloride is added. The mixture was stirred at room temperature for one hour, after which the substance was isolated after the HPD procedure described in Example 1. Exit L-Ititrrbenzyl 7 phenoxyacetamide-3 chloro-3-cepheme -4-carboxyate 6.2 b g
    30.3%, and the resulting substance is analytically identical to that of Example 1.
    PM ROM 15. {-nitrobenzyl 7 phenrxiacetamidr-3 chloro-3 cefem-t-carbr xylate. . .
     Phosphrr trichloride in volume, 63 ml is mixed with 20 ml of MP, after which the resulting mixture is stirred without cooling for min. Then an additional amount of DMF is added and the resultant product is mixed with 2.5t g
    solution of nitroben or 7-phenoxyacetamido-3-hydroxy-3-14epheme-sulfoxide carboxylate in 5 ml of DMF at -60 ° C.
    After this, the mixture is heated and stirred at this temp. Temperature for one hour. The mixture is then heated to ambient temperature and further stirred for one more hour. Allotment
    0 substances occur in accordance with the scheme of Example 1, and the result of which is 0.98 g of 4-nitrrbenzyl is obtained ... 7 phenoxyacetamido-h3-chloro-3 cephem-4-carboxylate, analytically ideal
    5% of the substance from Example 1 ew during 38.8%. .. :
    The starting 4-nitrobenzyl 7-phenoxyacetamido-3-hydroxy-3-cephem-4-carbr xylate eulfoxide is prepared as follows
    rbrazm
    0.8 g of 4-nitrobeneyl 7-f enP1 siacetamido-3-exomethylene-β-carboxylate is dissolved in 80 ml of methylene chloride and 0.12 ml of methanol is added. The solution is cooled in an atmosphere of nitrogen before and for a period of time: the miuta let the ozone bubbles through. The mixture is stirred for two minutes and then heated to Q ° C. Chromatographic analysis of the TOMfssro layer showed that exomethylenesophage was converted to 4-nitrobenzi-7 phenrxy-acetamido-3 hydroxy-3-cephem-carbroxy lat eulfoxide.
    Example 16. -nr) 1benzi 7-phenoxyacetamido-3 chloro-3 -cephem-4-carboxylate.
    I A reactive mixture composed;
    in accordance with the method of priming in example T, is evaporated to a volume of approximately 30 ml, after which fO ml of DMF is added. The mixture is then evaporated in vacuo to isolate the residual CRTs of the GHI methylene and methyrla. The remaining liquid is cooled to 0 ° C and 0.35 ml of phosphorus trichloride is added to it. After this, the reaction mixture is heated to ambient temperature and stirred for one hour and 5 minutes. The substance was isolated and purified in accordance with the Procedure used in Example 1, resulting in 0.22 g of nitrobenzyl 7 FenRxyacetamyl-3-chlorop-3-cephem-carbroxylate, which is analytically identical to the substance from Example 1. Exit product 43.3% of theoretical. Example 17 () Bonding p 7 phthalimido-3 chloro-3 Cefem-carbox lat. kr-nitrobenzyl 7 Phthalimido-3-hydroxy-3 cephem-carboxylate sulfoxide is diluted in dimethylforimide and the solution is cooled to an ice bath temperature. To the solution is added gradually while stirring; The scientific research institute 0.93 ml (10.5 mmol) of trichloride phosphorus and sending this addition all the reacting mixture is stirred for one hour. Then 70 ml of ice and water are added to the mixture, after which the precipitated substance is filtered. Then the substance is washed with water and dilute hydrochloric acid and dried to a weight of -nitro benzyl 7 phthalimido-3 chloro-3-cephem-carboxylate, 0 g. The substance is purified by chromatography on a column of silica gel (20 cm by elution with toluene. ethyl acetate (95: 5). Fractions containing 3-chloro compound are combined and evaporated to dryness under vacuum to obtain 2.70 g of purified substance. Sample -nitrobenzyl 7-phthalimido 3 chloro-3-cephem-carboxylate, obtained and purified according to the indicated method, gives the following elementary analysis for 22 ° C. eno: C 52.86, H 2.82, N8, tt, O 22.40; S 6.41; C1 7.0. Received,%: C 52.60 H 3.03, N8.29; Q 22, 56} S 6.1, ce 7.26. EXAMPLE 18 4-nitrobenzive 7 phenoxyacetamide-3-chloro-3-cephem i-carboxy at. In 20 ml of cold D4F, j & 63, g phosphorus trichloride and the resulting mixture is stirred for wtH under nitrogen at about 1000 ° C. After the mixture is cooled, 20 ml of DNF containing 7 g of nitrobenzyl 7 phenoxyacetates db-3okGi-3-heat are added dropwise. kap6okoksilat sulfoide with a temperature of -20 ° C. The mixture is stirred for one hour and then for another 1 6. ° hour at ambient temperature. The substance is isolated and purified according to the scheme of Example 1 to obtain 0.076 g -nitrobenzyl 7 Phenoxyacetamido-3-chloro-3-cephem-4-carboxylate at a yield of 15, which is identical to the substance of Example 1 by chemical composition. Approx 19. -nitro6enzyl 7-phenoxyacetamido-3-chloro-3-cefem-1a oxyl. 20 ml of DKP are cooled to about -50 ° C and 1.0 ml of cold phosgene is added thereto. For five minutes, the mixture is kept at Wasp and then degassed under nitrogen. Then the mixture of phosgene and DMF is cooled to -50 ° C in a bath of dry ice and acetone and 2.51 g of nitrobenzyl 7-phenoxyacetamido-3-hydroxy-3-cephem-4-carboxylate sulfide Oxidium added in a dropwise manner in DMF. . The mixture is stirred for one hour, after which the substance is separated by chromatography, in accordance with the scheme of Example 1, for a half-hour of 0.63 g of -nitrobenzyl 7-phenoxyacetamido-3-chloro-3-cephem-4-carboxylate, which is analytically identical to the substance obtained in Example 1. The actual yield from the calculated is 25. EXAMPLE 20 20 n -nitrobenzyl 7-phenylacetamido-3-chloro-3 cephem-4-carboxylate. . Fulfill the requirements of the basic process used in Example 1, a small amount of trichloride. phosphorus is added to cold DMF and stirred for a short time. Then, an amount of " -nitrebenzyl 7-phenyl-acetamido-3-hydroxy-3 cephem carboxylate sulfoxide is slowly added to the solution while stirring, and then the reaction mixture is again stirred and heated to ambient temperature. The substance is isolated and purified in accordance with According to the scheme of Example 1 for the preparation of 4-nitrobenzyl 7 Phenylacetamido-3-chloro-3-cephem-carboxylate.
    权利要求:
    Claims (7)
    [1]
    METHOD FOR PRODUCING 3-CHLOROCEPHEMES of the formula (D) where phenylacetyl or phenoxyacetyl *, '.
    Rj is a hydrogen atom or together in the nitrogen atom to which they are bonded, form a phthalimido radical by halogenation of the 3-oxo-Pheme compound 8 in the presence of dimethylformamide under anhydrous conditions when cooled or at room temperature, excluding the fact that, in order to simplify the process, a 3-hydroxycephemic compound of the formula is used and halogenation is carried out with phosphorus trichloride or Phosgene.
    [2]
    2. The method according to η. 1, the fact that the process is conducted - 1 at a temperature of from -65 ° C to room temperature.
    [3]
    3 · The method according to Claim 2. On the one hand, the process is conducted at room temperature. .
    [4]
    4. The way to pop. 1, the same as that. that halogenation is carried out with phosphorus trichloride. . . . ''
    [5]
    5. The method according to π. 1, with the exception that the process is conducted at a ratio of from 2 to 9 mol of phosphorus trichloride per T mol of the compound of formula (Q),
    [6]
    6. The method according to p. 5, so that the process is conducted at a ratio of from 3 to 4 mol of phosphorus trichloride per 1 mol of compound. expressions of the formula (P
    [7]
    7. The method according to η, 1, the same as the fact that they use a compound of formula (P), where R ^ is phenoxyacetyl, R 2 is a hydrogen atom, halogenation is carried out by phosgene and the process is carried out at a ratio of
    2 to 9 mol of phosgene per 1 mol of compound of the formula (.11) and at a temperature
    -60 - 0 ° С.
    Λ
    类似技术:
    公开号 | 公开日 | 专利标题
    SU1018586A3|1983-05-15|Method of producing 3-chlorocephems
    US4427587A|1984-01-24|Total synthesis of antitumor antibiotics BBM-2040A and BBM-2040B
    Boyd et al.1986|γ-Lactam analogues of carbapenems
    US4735937A|1988-04-05|8-oxo-5-thia-1-azabicyclo|oct-2-ene compounds
    US5072004A|1991-12-10|Synthetic conversion of bryostatin 2 into bryostatin 1
    CH624670A5|1981-08-14|Process for preparing an oxoazetidine derivative as a stereospecific intermediate for the synthesis of cephalosporins
    Saito et al.1974|The Reaction of Ethyl Ethoxymethylenecyanoacetate with Its Hydrazino Derivatives
    US3966738A|1976-06-29|Azetidine derivatives
    US4166816A|1979-09-04|Methods and intermediates for preparing cis-4-oxoazetidine intermediates
    CA1218650A|1987-03-03|Process for the synthesis of pyrido-imidazo-rifamycins
    KR890003840B1|1989-10-05|Process for preparing 8-holo-5,6-diakoxyquinazoine-2,4-diones
    US4103086A|1978-07-25|8-Oxo-4-thia-1-azabicyclo |-oct-2-ene derivatives
    Ernest1979|2‐Oxocephems. Synthesis and Properties of 7‐Acylamino‐2‐oxocephem‐4‐carboxylic Acids
    US4525304A|1985-06-25|Process for preparing oxazolinoazetidinones
    US3960851A|1976-06-01|Preparation of desacetoxy-cephalosporin sulfoxides from penicillin sulfoxides
    US4064137A|1977-12-20|Penicillin and cephalosporin derivatives and process for preparing the same
    SU1039444A3|1983-08-30|Process for preparing 1-oxadethia cephalosporin
    US4430498A|1984-02-07|8-Oxo-5-thia-1-azabicyclo|oct-2-ene compounds
    US3962277A|1976-06-08|Acetidine derivatives
    US4677098A|1987-06-30|Substituted dihydro-1H-pyrolizine-3,5|-diones
    SU735169A3|1980-05-15|Method of preparing cephalosporin derivatives
    US3705160A|1972-12-05|Thiazacyclic hydroxy compounds and process for their manufacture
    JPH05201967A|1993-08-10|Production of 4-substituted propylazetidin-2-one derivative
    HU187976B|1986-03-28|Process for producing 5,11-dihydro-11-//4-methyl-1-piperazinyl/-acetyl/-6h-pyrido/2,3-b//1,4/benzodiazepin-6-one
    SUGAI et al.1983|A New Efficient Method for Conversion of Corticosteroid 17α, 21-Cyclic Ortho Esters to 17α-Acyloxy-21-chloro-21-deoxy Derivatives
    同族专利:
    公开号 | 公开日
    BG28068A3|1980-02-25|
    FR2362145B1|1980-02-15|
    CS192588B2|1979-08-31|
    US4115643A|1978-09-19|
    DE2735454A1|1978-02-23|
    GB1582044A|1980-12-31|
    DD131858A5|1978-07-26|
    RO71908A|1981-11-24|
    CA1099256A|1981-04-14|
    IL52416A|1980-02-29|
    HU179459B|1982-10-28|
    IE45158L|1978-02-16|
    FI772339A|1978-02-17|
    NL7709055A|1978-02-20|
    JPS5323994A|1978-03-06|
    FI66873B|1984-08-31|
    ES461587A1|1978-06-01|
    FR2362145A1|1978-03-17|
    PL110242B1|1980-07-31|
    IE45158B1|1982-06-30|
    CH630924A5|1982-07-15|
    IL52416D0|1977-08-31|
    JPS6120556B2|1986-05-22|
    FI66873C|1984-12-10|
    BE857244A|1978-01-30|
    PL200289A1|1978-05-08|
    DE2735454C2|1992-12-10|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US3641014A|1968-10-03|1972-02-08|Lilly Co Eli|Reduction of delta3-cephalosporin sulfoxides|
    US3925372A|1973-02-23|1975-12-09|Lilly Co Eli|Alpha-aminoacyl-3-halo cephalosporins|
    US3962227A|1973-02-23|1976-06-08|Eli Lilly And Company|3-halo cephalosporins|
    AR208068A1|1973-02-23|1976-11-30|Lilly Co Eli|A PROCEDURE FOR PREPARING DERIVATIVES OF 7-ACILAMIDO-3-HALO-CEFEM-4-CARBOXYL ACIDS, THE ESTERS AND THE PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF|
    YU36970B|1973-02-23|1984-08-31|Lilly Co Eli|Process for obtaining 7--acylamido-3-halocephalosporins|AT342197B|1975-02-20|1978-03-28|Ciba Geigy Ag|NEW PROCESS FOR PRODUCING 3-CEPHEM CONNECTIONS|
    US4223133A|1979-02-01|1980-09-16|Eli Lilly And Company|Cephalosporin reduction process|
    US4271305A|1979-02-01|1981-06-02|Eli Lilly And Company|Thiazolinoazetidinones and process therefor|
    US4226986A|1979-02-01|1980-10-07|Eli Lilly And Company|Process for halogenation of β-lactam compounds|
    US4237279A|1979-07-27|1980-12-02|Eli Lilly And Company|Crystalline 3-hydroxycephalosporin solvates|
    US4281117A|1980-09-04|1981-07-28|Eli Lilly And Company|Process for 3-chloro cephalosporin nucleus|
    US5159071A|1990-09-06|1992-10-27|Ranbaxy Laboratories Limited|Process for the manufacture of 7-amino-3-exomethylene-3-cepham-4-carboxylic acid ester|
    US5350845A|1992-04-08|1994-09-27|Eli Lilly And Company|Process for preparing 7-substituted-amino-3-hydroxy-3-cephem-4-protected carboxy-sulfoxide esters|
    IN181695B|1992-08-10|1998-09-05|Ranbaxy Lab Ltd|
    US5604222A|1993-12-27|1997-02-18|Lupin Laboratories, Ltd.|Method for the preparation of 2-chloro sulfinyl azetidinones|
    US5578721A|1994-07-11|1996-11-26|Lupin Laboratories Limited|Process for preparation of 3-exomethylene cepham sulfoxide esters|
    KR100390551B1|1996-08-22|2003-11-17|주식회사 코오롱|Method for manufacturing 3-halomethyl-3-cephem-4-carboxylate 1-oxide|
    CN101190921B|2007-11-27|2010-05-19|吉林省石油化工设计研究院|Method for preparing p-nitrobenzyl-7-phenoxyacetamido-3-exomethylenecepham-4-carboxylate-1-beta-oxide|
    CN102443014B|2011-12-29|2014-07-09|上海右手医药科技开发有限公司|3-cefaclor derivative as well as synthesis method and application thereof in preparation of cefaclor|
    CN103588790A|2013-11-29|2014-02-19|中国科学院长春应用化学研究所|Preparation method of 7-amino-3-chloro-3-cephem-4-carboxylic acid-p-nitrobenzyl ester|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US71494876A| true| 1976-08-16|1976-08-16|
    [返回顶部]