• 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:
    A compound represented by the formula (II) epimerizes by the action of a base and the product is precipitated for shift- wherein Ar is an optionally substituted aryl or heterocyclic group; Tet is an optionally substituted tetrazolyl group and B1 and B2 each is ing the equilibrium to yield the corresponding epimer represented by the formula (I): an ester forming group in the field of penicillin or cephalosporin chemistry.
    公开号:SU1225488A3
    申请号:SU833613971
    申请日:1983-07-01
    公开日:1986-04-15
    发明作者:Нарисада Масаюки；Оноуе Хироси；Охтани Мицуаки；Ватанабе Фумихико
    申请人:Сионоги Энд Ко.,Лтд (Фирма)；
    IPC主号:
    专利说明:

    This invention relates to a new process for the preparation of esters of S-epimer 7ft-malonamido-7c-methoxy-3- (1-methyltetrazol-5-ylthiomethyl) -1- children-1-oxa-3-cephem-4-carboxylic acid, which are intermediates in the synthesis of antimicrobial agents.
    The aim of the invention is to increase the purity and stability of the target product.
    Example 1. In the first stage, to a solution of U -Co-para-hydroxyphenylmalon-amido) -7o-methoxy-3- (1-methyl-5-tetrazolyl) thiomethyl-1-child-1-oxa-3-cephem- 4-carboxylic acid (5.20 g in 40 ml of methanol) cooled to 0 ° Cj, 93 ml of dichloromethane containing 5% diphenyldiazomethane are added dropwise. After 1 hour of stirring under ice cooling, this solution is concentrated under reduced pressure of NS1. The resultant material is purified by chromatography on a gel, to obtain the corresponding (is diphenylmethyl ester (8.5 g) from the fractions eluted with a mixture (2: 1) of benzene and ethyl acetate. This product is a mixture (1: 1) (R) - and (3) -epimers at the 3 /.-Position of the side chain attached at position 7. A part of the product (3.0 g) is dissolved in a mixture of 20 ml of ethyl acetate and O, 1 ml of pyridine and left at room temperature during the day. The precipitated crystals are collected by filtration in order to obtain the desired (5) -epim p (4.45 g). Yield 75%, pro- contains 2 molar equivalents of crystal ethyl acetate, mp 119-122 ° C,
    NMR spectrum in deuteroacetone, chem. shift; 1.18 (triplet, 7 Hz, 6H), 1.92 (s, 6H), 3.37 (singlet, 3N), 3.88 (s, 3N); 4.05 (quartet, i 7 Hz, 4H) - 4.30 (s, 2H); 4.60 (s, 2H), 4.97 (C, 1H); 5.12 (s, 1H); singlets 6.72 + 6.85 (A-part of the quartet AB, Hz, 2H) 6.85 (s, 1H) i 6.9.2 (s, 1H), 7.1-7.9 (mutiplet, 23H )
    m-NMR spectrum in deuteroapetone 1, xi shift: 3.37 (s, 3N); 3.88 (s, 3N); 4.30 (s „2H), 4.60 (s, 2H) L 4.97 (s 1H); 5.12 (s, 1H); 6.72 + 6.85 - with
    since years (A-part of the quartet AB, Hz 2H); 6.85 (s, 1H); 6.92 (s, 1H); 7 J, 1-7 59 (multiplet, 32H),
    PRI me R 2, By the interaction of 7p (c-para-hydroxyphenylmal
    (0 amido) -7d MeTOKCH-3- (1-methyl-5-tetrazolyl) thiomethyl-1-child-1 oxa-3-cephem-4-carboxylic acid with para-.nitrophenyl diazomethane prepared from p-nitrobenzaldehyderazine by
    15 oxidation with hydrogen peroxide, the corresponding α-para-nitrobenzyl-ester can be considered (mixture of (K) - (8) -epimers). This mixture of the crista is licked out of 5 parts by weight. dichloromethane,
    20 containing lutidine, in order to ensure the formation of (S) 25
    thirty
    epimera, melting point 12–123 ° C.
    The same product itself can be prepared by treating the same material in the form of disodium salt with a molar equivalent of para-ni-trobenzyl bromide in a solution of N, N-di-tilacetamide for 1.5 hours, and then crystallizing a product of 5 weight dichloromethane containing 0.1% quinoline: a, melting point 120 @ 123 ° C,
    NMR spectrum in deuteroacetone, chi shift; 3.33 (singlet, ZN); 3.92 (s, 3N); 4.15 + 4,, 45 singlets (A- part of the quartet ABg, Hz, 2H); 4.62 (s; 2H), 4.95 (s, P), 5.08 (s, 1H); 5.18 + 5, inlets (A - part of the quartet ABg; 14 Hz, 2H) 5.45 (s, 2H); 6.82 + 7.32 singlets (A - part of the quartet ABg, 8.5 Hz 4H); 7.57-8.32 (multiplet, YUN).
    Example 3, To a vapor solution of methoxybenzyl iodide prepared from para-methoxybenzyl chloride. (37.59 g) and 35.97 g of sodium iodide in a solution of 300 ml of dimethylformamide at 0 ° C for 1 h, add sodium salt of 7p-M - (R5) -para-ca
    40
    45
    f, f - -,,. - -At the second stage by means of a crisphenylmalonamido) -7 (X-methoxy-3-1 1 -ization of the (R) -epimer or (8) -epimemethyl-5-tetrazolyl) thiomethyl-1-de
    pa (3.0 g) from 30 ml of benzene containing Oh, 1 ml of pyridine, get one
    the same (8) epimer (about 2.5 g).
    Yield 73%, This product contains
    1.5 molar equivalents of crystalline benzene, melting point 55
    thia-1 oxa-3-defem-4-carboxylic acid (33.87 g) and 4.16 ml of triethylamine. After stirring at room temperature for 2 hours, the mixture is diluted with ethyl acetate, washed with dilute hydrochloric acid and water, dried over sulfate-sodium
    neither 119-122 s.

    254882
    m-NMR spectrum in deuteroapetone 1, chemical, shift: 3.37 (s, 3N); 3.88 (s, 3N); 4.30 (s 2H); 4.60 (s, 2H) L 4.97 (s, 1H); 5.12 (s, 1H); 6.72 + 6.85 - sings years (A-part of the quartet AB, Hz, 2H); 6.85 (s, 1H); 6.92 (s, 1H); 7 J, 1-7 59 (multiplet, 32H),
    PRI me R 2, by reacting 7p (c-para-hydroxyphenylmalone (0 amido) -7d MeTOKCH-3- (1-methyl-5-tet, dissolved) thiomethyl-1-children-1 oxa-3-cephem- 4-carboxylic acid with para-.nitrophenyldiazomethane obtained from p-nitrobenzaldehyderazine by
    15 oxidation with hydrogen peroxide, it is possible to blame the corresponding α-para-nitrobenzyl-ester (mixture of (K) - (8) -epimers). This mixture is crystallized from 5 parts by weight. dichloromethane,
    20 containing lutidine, in order to provide education (S)
    epimera, melting point 120-123 ° C.
    The same product itself can be prepared by treating the same material as the disodium salt with a molar equivalent of para-nitrobenzyl bromide in a solution of N, N-dimethylacetamide for 1.5 hours, and then crystallizing a product of 5 parts by weight , dichloromethane containing 0.1% quinoline: a, melting point 120 - 123 ° C,
    NMR spectrum in deuteroacetone, chemical, shift; 3.33 (singlet, ZN); 3.92 (s, 3N); 4.15 + 4,, 45 singlets (A- part of the quartet ABg, Hz, 2H); 4.62 (s; 2H), 4.95 (s, P), 5.08 (s, 1H); 5.18 + 5, inlets (A - part of the quartet ABg; 14 Hz, 2H), 5.45 (s, 2H); 6.82 + 7.32 singlets (A - part of the quartet ABg, 8.5 Hz, 4H); 7.57-8.32 (multiplet, YUN).
    Example 3, To a solution of paramethoxybenzyl iodide prepared from p-methoxybenzyl chloride. (37.59 g) and 35.97 g of sodium iodide in a solution of 300 ml of dimethylformamide at 0 ° C for 1 h, 7-M - (R5) -para-hydroxy di-sodium salt is added.
     , - -
    thia-1 oxa-3-defeme-4-carboxylic acid (33.87 g) and 4.16 ml of triethylamine. After stirring at room temperature for 2 hours, the mixture is diluted with ethyl acetate, washed with dilute hydrochloric acid and water, and dried over sulfate-sodium
    ri and concentrate to dryness under reduced pressure. The residue is dissolved in a mixture (1: 1) of benzene and ethyl acetate and passed through a pad of silica gel. This solution is concentrated to dryness, the resulting solid is dissolved in 100 ml of dichloromethane, containing 0.1% triethylamine, and diluted with benzene before crystallization (moderately dissolving precipitation solution) in order to collect the crystals. filtration and flush with benzene to give the corresponding isoprotein methoxy benzyl ester (S) -3n HMepia (34 g), melting point 95-. Yield 74%.
    IR spectrum in chloroform v: 3600; 3410; 3328; 1786; 1695 cm
    NMR spectrum in deuteroacetone, chem. shift: 3., 28 (s, 3N); 3.77 (s, 6H); 3.94 (s, 3N); 4.13 + 4.40 doublets (AB-quartet, 5 Hz, 2H); 4.78 (s, 1H) J 5.00 (s, 1H) i 5.07 (s, 2H), 5.21 (s, 2H); 6.67-7.48 (m, 12H); 8.05 (s, 1H); 8.26 (s, 1H).
    Example 4. Solution of difenstmethyl ester of 7 | 1-amino-7Y-methoxy-3- (1-methyl-5-tetrazolyl) thiomethyl-1-decya-1-oxa-3-cephem-4-carboxylic acid (107 mg) , 70 μl of pyridine, 84 mg of para-tetrahydropyranyloxyphenylmalonic acid mono-paramethoxybenzyl ester and 20 ml of phosphorus oxychloride in 1 ml of dichloromethane are cooled at -5 ° C, stirred for 30 min and mixed with 70 μl of aqueous 5% sodium bicarbonate solution. After evaporation of dichloromethane under reduced pressure, the residual solution is extracted with ethyl acetate. The extract is washed with 2n. hydrochloric acid and water, dried over sodium sulfate and concentrated under reduced pressure. The residue is dissolved in 2 ml of acetone, cooled at 0 ° C, acidified with three drops of concentrated hydrochloric acid and stirred for 45 minutes. The reaction mixture is basified with 0.9 ml of 5% aqueous sodium bicarbonate solution and stirred for 1 hour. The solution is diluted with water (moderately dissolving precipitation solution) until the precipitate starts, which is collected by filtration, washed with a mixture of acetone and water (1 : 1) and with water and dried, obtaining (8) -epimer complex diphenyl-
    2254884
    (o1.-para-methoxy-benzyloxycarbonyl-n-hydroxyphenyl-ethyl-) -7ol.-methoxy-3- (1-methyl-5-tetrazolyl) -thiomethyl-1-de-1-oxa-3-cent methyl ester - with fem-4 carboxylic acid (102 mg).
    NMR spectrum in deuteroacetone, chem. shift: 3.23 (singlet, MN); 3.72 (s, 3N); 3.87 (s, 3N); 4.23 (s, 2H), 4.53 (s, 2H); 4.83 (s, 1H); 5.03, 0 (s, 2H); 5.13 (s, 1H); (A - part of, t 9 Hz, 2H); 6.87 (s, ib); 6.88 (A - part from ,, Hz, 2H); 7.13-7.67 (multiplet, 14H); -9.30 (s, 1H). 4 seconds This precipitate is recrystallized
    t
    from ethyl acetate and dried for 7 hours in a stream of air, to obtain monohydrate crystals, melting point 142-144 ° C.
    2Q Spectrum in deuteroacetone,: 3.38 (s, 3N); 3.80 (s, 3N); 3.93 (s, 3N); 4.32 (s, 2H); 4.63 (s, 2H), 4.83 (s, 1H); 5.11 (s, 3N); 6.73 + + 6.87 singlets (A - part from quarte25 and AB, Hz, 2H), 6.83 + 6.96 singlets (And - part of quartet AB, Hz, 2H); 6.92 (s, 1H); 7.19-7.79 (m, 21H).
    X-ray spectrum (Cu: N, 40 kV, 20 mA, 5405) angle 20: 6,1
    ,, weak peak; 8.5 Medium Peak, 10.1 Medium, 10.6 Medium; 11.5 weak
    12.2 average, 14.3 strong, 15.1 medium, 15.5 strong, 16.9 medium,
    18.3 very strong, 19.6 medium, 20.6 very strong, 21.5 weak,
    35 22.7 very strong, 23.7 weak,
    25.0 average, 26.6 weak, 27.4 weak, 27.8 weak, 29.1 medium, 30.8 weak, 31.8 weak, 33.1 weak, 33.9 weak, 34.6 very weak .
    40
    35.4 weak, 36.0 very weak.
    36.3 is very weak, 37.1 is very weak.
    Example 5. Under the reaction conditions similar to those described in example e 4, complex diphenylmethyl ether
     7f -amino-7Y-methoxy-3- (1-methyl-5-tetrazolyl) -thiomethyl-1-children-1-oxa-3-cephem-4-carboxylic acid and (R, S) - (with (-diphenylmethoxycarbonyl p-tetrahydropyranyloxyphenyl acetyl chloride
    5 gives complex diphenylmethyl ester 7p- (oi-diphenylmethoxycarbonyl-p-tetrahydropyranyloxyphenylacetamido) -7o (-methoxy-3- (1 -methyl-5-tetrazolyl) thiomethyl-1-children-1-oxa-3-cephem-4 -
    55 carboxylic acids (mixture of (R) - and (8) -epimers), which are hydrolyzed with hydrochloric acid and recrystallized from smgsi, 20 parts by weight benzene and
    10% pyridine to provide (3) 7p- (c.-diphenylmethoxycarbonyl-p-hydroxyphenylacetamido) diphenyl methyl ester epimer -7Y.methoxy-3- (1-methyl 5-tetrazolyl) thiometyl-1- 1-ox.3-cephem-4-carboxylic acid children. This product is identical to the product of example 1.
    PRI me R 6o Under conditions similar to the reaction described in the example, AdSlphenyl diphenylmethyl ether 7 / $ - ag-shno-Us-methoxy-3- (1-methyl 5-tetrazolsh1) -thiomethyl 1 children- 1 oxa-3-cephem 4k, arbonic acid and (RS) -o.para-1x-etoxybenzyloxycarbonyl-p-hydroxyphenylacetyl chloride give complex diphenylmethyl ester 7p- (2-p-hydroxyphenyl-2-n-methoxybenzyloxycarbonyl-pepetamldo ) -7c-methoxy-3- (1-methyl-5 tetrazolyl) thiomesh-1-1-denya-1 ™ oxa 3-cephem 4-ka.rboxylic acid L mixture (R) and (3): epimers) that is crystallized from a mixture of 5 weight, h. ethyl acetate and 10% diethanolamine 5 to obtain (3) -epimer in 90% yield. This product is identical to the product of Example 4.
    Example 7. Crystallization of 7p- (2-g1 hydroxyphenyl 2- (5 indanyl) oxycarbonyl dehyd4-4) 7c-methoxy-3- (1-methyl-5 tetrazolyl) thiomethyl-1-children-1 diphenylmethyl ester -ox-3 defeme 4 - carboxylic acid (a mixture of (R) - and (8) epimers, 230 mg) from a mixture of 3 vol-ch. chloroform to the solution containing 0.05% dizthanolamine (slowly adding ether as a moderately dissolving solvent before crystallization) gives 88 mg of the (8) epimer, melting point 114-116 C.
    IR spectrum in chloroform, y: 3590; 3335; 1789; 1736, 1722; 1700; - 1601 cm.
    Spectrum in deuteroacetone, S; 2.1 (multiplet, 2H), 2.87 (triplet, Hz, 4H), 3.43 (s, 3N); 3, .91 (with „ЗН); 4.31 (s, 2H.); 4.65 (s, 2H) J 5.07 (s, 1H); 5.13 (s, 1H), 6.92 (s, .ZN); 6.8-7.7 (m, 16H); 8.25 (m, 1H). Example 8 In the first stage to a stirred solution of 7-bepzamido 7Y methoxy-3- (1-methyl-5 tetrazolyl) tnomethyl-1-child-1-oxa-3-ce-, fem 4 carboxylic acid diphenylmethyl ester (6.13 g), 1.77 mp of pyridine and 4.2 g of phosphorus chloride were added to 50 ml of methylene chloride and the mixture was boiled under reflux.
    s 0 5
    Q
    0
    five
    fniKOM for 1 h under nitrogen atmosphere. The reaction mixture is cooled to (-15) - (-10) C, diluted with methanol (200 ml) and stirred for 3 h at 0 ° C. The reaction mixture is stirred for 15 min, mixed 8.28 ml diethylamine. The reaction mixture is then diluted with dichloromethane, washed with water, dried and concentrated. The residue is diluted with a solution so that the diphenylmethyl ester 7, the amino is 7c crystallizes, the 1-ketoxy-3- (1-methyl-5-- Tetra sol-yl) thiomethyl -1-child-1-oxa-3-cephem-4 carboxylic acid (3.97 g), melting point 160,162 s (s,).
    To a solution of 1.02 g of the first stage product obtained above, 0.7 ml, pyridine and 1.0 g of 2 / p- (p-methoxybenzyl) oxyphenyl / -2-p-methoxybenzi-p-carboxy-1-acetic acid in dichloromethane are added 0 , 2 ml of phosphorus oxychloride with stirring at a temperature of 12 ° C, the mixture is stirred for 30 minutes at. The mixture was neutralized with aqueous 5% sodium bicarbonate solution (7 ml), concentrated and extracted with ethyl acetate. The extract is washed with 2N hydrochloric acid and water, dried over sodium sulfate, and concentrated. The resulting mixture of (R) and (8) -epimers crystal. scooping from 30 ml of benzene containing 0.1% picoline to obtain (3) - epimer of diphenylmethyl ester 7p- (2-p- / p-methoxybenzyloxn / phenyl-2-p-methoxybenzyloxycarbonylade agdado) -7c-methoxy-3- (1-methyl 5-tetrazolyl) thiomethyl-1-children-1-oxa-3-; cephem-4-carboxylic acid (1.6 g) „
    IR spectrum in chloroform,); 1792, 1725; 1700 cm.
    NMR spectrum in chloroform, o; Зр45 (с, ЗН); 3.78 (s, 6H); 3.82 (s, RN) - 4.27 (broad s, 2H): 4.57 (broad s. MN) - 4.98 (s, 2H); (s, 1H), 5.13 (s, 2H),
    Example 9. A solution of diphenylmethyl-1-ester 7p- (2-diphenylmethoxycarbonyl-2- (3-thienyl) -acetamido) - 7 ° (methoxy-3- (1-methyl-5-tetra zolyl) thiomethyl-1 -dethia-1-oxa-3-cephem of 4-carboxylic acid in benzene, containing 0.1% pyridine (3 parts by weight) holding out g in ice (0 ° С) for 2 hours at room temperature for 5 hours to separate the crystals., Which are collected by filtration, and receive the corresponding
    (3) Epimer with a yield of 43%. The product is NMR spectrum in deuteroacetone, (i:
    contains 1/3 molar equivalent 3,43 (s, 3N); 3.83 (s, 3N); 4.23
    crystalline benzene, temperature- (s, 2H); 4.53 (s, 2H) 55.08 (s, 1H),
    melting 85-92 ° C. 5 (s, 1H); 6.85
    IR spectrum in chloroform: 3405, (s, 1H); 7.07-7.70 (m, 24H).
    YU; 1790; 1723; 1704; 1633; 1602;
    7; 1498; 1166.
    3330 1587
    权利要求:
    Claims (2)
    [1]
    1. METHOD FOR PRODUCING S-EPIMER 7 ETHERO ETHERS
    SOOV *
    Ar-s
    I n
    Ν — N CH 2S HELL soybean 2 7 sn3 where Ar, B 1 and B 2 have the indicated values 0CH3
    C0NH {epimerization is subjected to epimerization under the action of a base selected from the group consisting of sodium hydrogen carbonate, sodium carbonate, triethylamine, diethanolamine, pyridine, picoline, quinoline, lutidine and collidine, in a solvent selected from the group consisting of acetone, benzene, dichloromethane / chloroform, diethyl ether, ethyl acetate, methanol and water, or mixtures thereof at a temperature of from 0 ° C to room temperature for 1-24 hours after N — N ch 2 s4 D sow 2 ΐ sn 3
    - n-hydroxyphenyl, n-methoxy-
    - (benzyloxyphenyl, n-tetrahydropyranoloxyphenyl or 3-thienyl, and B 2 is an ester forming group independently of one another, such as diphenylmethyl, p-methoxybenzyl, nitrbenzyl or indanyl, where Ar is in 4 by isolating the target product by precipitation by crystallization and / or concentration.
    [2]
    2. The method of pop. 1, characterized in that the precipitation is carried out by adding a solvent such as water, benzene or ether.
    类似技术:
    公开号 | 公开日 | 专利标题
    SU1225488A3|1986-04-15|Method of producing esters of s-epimer of 7beta-malonamido-7alpha-methoxy-3-|-1-dethia-1-oxa-3-cephem-4-carboxylic acid
    SU791246A3|1980-12-23|Method of preparing derivatives of 7-/2-|-2-alkoxyiminoacetamido/-3-cephem-4-carboxylic acid
    EP1767538B1|2014-05-07|Process for producing 1-oxacephalosporin-7alpha-methoxy-3-chloromethyl derivative
    FI84268C|1991-11-11|7-Amino-3-propenylcephalosporanoic acid and its esters and a process for their preparation
    US4147863A|1979-04-03|7-D-|-mandelamido-3-|vinyl-3-cephem-4-carboxylic acid
    US4112087A|1978-09-05|Cephalosporin type antibacterials having a substituted propenyl group in the 3-position
    US4148997A|1979-04-10|7-[Sulfomethyl)phenyl]acetamidocephalosporin derivatives
    WO1991009037A1|1991-06-27|Process for producing 3-substituted thio-3-cephem compound
    SU797579A3|1981-01-15|Method of preparing acid amides or their salts with alkaline metals or trialkylamines
    US4139701A|1979-02-13|7-Amino-3-|cephalosporin intermediates
    US4959495A|1990-09-25|Process for the preparation of intermediates used to produce aminothiazoloximino cephalosporins
    US4107433A|1978-08-15|Phthalidyl ester of 3-carbomoyloxy cephalosporin derivatives
    KR790001503B1|1979-10-24|Process for preparing 3-cephalosporing esters
    KR890001285B1|1989-04-28|Process for preparing cephalosporin derivatives
    US4866169A|1989-09-12|3-substituted-8-oxo-7-substituted-thioxomethylamino-5-thia-1-azabicyclo-|oct-2-ene-2-carboxylic acid, diphenylmethyl esters
    SU953983A3|1982-08-23|Process for producing cephalosporin derivatives
    US4148995A|1979-04-10|Process for preparing cephem lactones for cephalosporin-type antibiotics
    JP2571059B2|1997-01-16|Method for producing 1,3,4-tri-O-acyl-2-deoxy-β-D-erythro-pentapyranose
    IE43912B1|1981-07-01|7-methoxycephalosporin derivatives and process for the preparation thereof
    SE412237B|1980-02-25|PROCEDURE FOR THE PREPARATION OF NEW 3-HALOGENEYMETHYL-DELTA? 723-CEPHALOSPORINE SULPHOXIDES
    US4226806A|1980-10-07|7-[|phenyl]acetamidocephalosporin derivatives
    DK144886B|1982-06-28|METHOD OF MANUFACTURING CEPHALOSPORINESTERS
    US4018761A|1977-04-19|Thio-β-lactam cephalosporins
    US4018760A|1977-04-19|Thio-β-lactam cephalosporins
    SU980625A3|1982-12-07|Process for producing cephalosporin compounds
    同族专利:
    公开号 | 公开日
    CA1192193A|1985-08-20|
    FI832407A0|1983-06-30|
    EP0098545A1|1984-01-18|
    DE98545T1|1984-08-16|
    DD210052A5|1984-05-30|
    IE55767B1|1991-01-16|
    AT19401T|1986-05-15|
    US4504658A|1985-03-12|
    GB8317634D0|1983-08-03|
    DK160502B|1991-03-18|
    AU564850B2|1987-08-27|
    CS244940B2|1986-08-14|
    GB2124217B|1985-09-04|
    FI832407L|1984-01-03|
    NZ204627A|1986-04-11|
    CS503683A2|1985-09-17|
    RO86355A|1985-03-15|
    KR840005450A|1984-11-12|
    JPH0149271B2|1989-10-24|
    DK160502C|1991-08-26|
    EG16539A|1989-03-30|
    AU1649683A|1984-01-05|
    DK304983D0|1983-07-01|
    YU44011B|1990-02-28|
    DE3363161D1|1986-05-28|
    IE831527L|1984-01-02|
    PT76973A|1983-08-01|
    KR890000812B1|1989-04-08|
    PL141782B1|1987-08-31|
    PH21139A|1987-07-27|
    JPS597193A|1984-01-14|
    HU187944B|1986-03-28|
    ES523774A0|1984-11-01|
    DK304983A|1984-01-03|
    YU144583A|1986-02-28|
    GR78620B|1984-09-27|
    NO832387L|1984-01-03|
    ES8500954A1|1984-11-01|
    PT76973B|1986-01-24|
    GB2124217A|1984-02-15|
    IL69146A|1987-01-30|
    ZA834495B|1984-07-25|
    PL242776A1|1984-08-13|
    RO86355B|1985-03-31|
    AR242391A1|1993-03-31|
    BG37526A3|1985-06-14|
    EP0098545B1|1986-04-23|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US3719667A|1970-08-24|1973-03-06|Lilly Co Eli|Epimerization of 6-acylamido and 6-imido penicillin sulfoxide esters|
    US4167630A|1975-12-24|1979-09-11|Merck & Co., Inc.|Process for epimerizing beta-lactam antibiotic compounds, and related products|
    CA1085392A|1976-03-25|1980-09-09|Masayuki Narisada|Arylmalonamido-1-oxadethiacephalosporins|
    US4234596A|1976-11-19|1980-11-18|Merck & Co., Inc.|3--6--7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid|
    US4259485A|1979-04-24|1981-03-31|Eli Lilly And Company|Crystallization process|
    US4252953A|1979-05-01|1981-02-24|Eli Lilly And Company|Antibiotic crystalline epimer|
    US4320055A|1980-04-07|1982-03-16|Eli Lilly And Company|Process for penicillin epimerization|
    JPS6364405B2|1980-06-23|1988-12-12|JPS60123490A|1983-12-07|1985-07-02|Shionogi & Co Ltd|Malonyloxacephem carboxylic acid derivative|
    US4998060A|1989-07-12|1991-03-05|Pacific Scientific Company|Fault indicator with hot stick clamping mechanism|
    JP2006028154A|2004-06-14|2006-02-02|Sumitomo Chemical Co Ltd|Method for producing optically active compound|
    CN102260280A|2010-05-28|2011-11-30|上海医药工业研究院|Preparation method of latamoxef disodium|
    EP2630191A4|2010-10-20|2015-05-20|Sirrus Inc|Synthesis of methylene malonates substantially free of impurities|
    US9828324B2|2010-10-20|2017-11-28|Sirrus, Inc.|Methylene beta-diketone monomers, methods for making methylene beta-diketone monomers, polymerizable compositions and products formed therefrom|
    US10414839B2|2010-10-20|2019-09-17|Sirrus, Inc.|Polymers including a methylene beta-ketoester and products formed therefrom|
    WO2013059473A2|2011-10-19|2013-04-25|Bioformix Inc.|Multifunctional monomers, methods for making multifunctional monomers, polymerizable compositions and products formed therefrom|
    JP6553505B2|2012-03-30|2019-07-31|シラス・インコーポレイテッド|Composite and laminate articles and polymerization systems for making them|
    EP3848402A1|2012-03-30|2021-07-14|Sirrus, Inc.|Ink and coating formulations and polymerizable systems for producing the same|
    CA2869108A1|2012-03-30|2013-10-03|Bioformix Inc.|Methods for activating polymerizable compositions, polymerizable systems, and products formed thereby|
    WO2013181600A2|2012-06-01|2013-12-05|Bioformix Inc.|Optical material and articles formed therefrom|
    EP2920231B1|2012-11-16|2020-05-06|Sirrus, Inc.|Plastics bonding systems and methods|
    EP2926368B1|2012-11-30|2020-04-08|Sirrus, Inc.|Electronic assembly|
    WO2014110388A1|2013-01-11|2014-07-17|Bioformix Inc.|Method to obtain methylene malonate via bis malonate pathway|
    US9279022B1|2014-09-08|2016-03-08|Sirrus, Inc.|Solution polymers including one or more 1,1-disubstituted alkene compounds, solution polymerization methods, and polymer compositions|
    US9249265B1|2014-09-08|2016-02-02|Sirrus, Inc.|Emulsion polymers including one or more 1,1-disubstituted alkene compounds, emulsion methods, and polymer compositions|
    US9315597B2|2014-09-08|2016-04-19|Sirrus, Inc.|Compositions containing 1,1-disubstituted alkene compounds for preparing polymers having enhanced glass transition temperatures|
    US10501400B2|2015-02-04|2019-12-10|Sirrus, Inc.|Heterogeneous catalytic transesterification of ester compounds with groups reactive under transesterification conditions|
    US9416091B1|2015-02-04|2016-08-16|Sirrus, Inc.|Catalytic transesterification of ester compounds with groups reactive under transesterification conditions|
    US9334430B1|2015-05-29|2016-05-10|Sirrus, Inc.|Encapsulated polymerization initiators, polymerization systems and methods using the same|
    US9217098B1|2015-06-01|2015-12-22|Sirrus, Inc.|Electroinitiated polymerization of compositions having a 1,1-disubstituted alkene compound|
    US9518001B1|2016-05-13|2016-12-13|Sirrus, Inc.|High purity 1,1-dicarbonyl substituted-1-alkenes and methods for their preparation|
    US9617377B1|2016-06-03|2017-04-11|Sirrus, Inc.|Polyester macromers containing 1,1-dicarbonyl-substituted 1 alkenes|
    US9567475B1|2016-06-03|2017-02-14|Sirrus, Inc.|Coatings containing polyester macromers containing 1,1-dicarbonyl-substituted 1 alkenes|
    US10196481B2|2016-06-03|2019-02-05|Sirrus, Inc.|Polymer and other compounds functionalized with terminal 1,1-disubstituted alkene monomer and methods thereof|
    US10428177B2|2016-06-03|2019-10-01|Sirrus, Inc.|Water absorbing or water soluble polymers, intermediate compounds, and methods thereof|
    KR102115644B1|2017-09-13|2020-05-27|주식회사 동도물산|Method of manufacturing 7α-alkoxy oxacephem intermediate compound|
    CN112480147A|2019-09-12|2021-03-12|杭州森泽医药科技有限公司|Latamoxef intermediate solvate and preparation method and characterization thereof|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    JP57116048A|JPH0149271B2|1982-07-02|1982-07-02|
    [返回顶部]