GB2056988A - Oxime Derivatives of 2-(2- tritylamino-thiazolyl)-acetic Acid and Alkyl Esters Thereof - Google Patents
Oxime Derivatives of 2-(2- tritylamino-thiazolyl)-acetic Acid and Alkyl Esters Thereof Download PDFInfo
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- GB2056988A GB2056988A GB8029620A GB8029620A GB2056988A GB 2056988 A GB2056988 A GB 2056988A GB 8029620 A GB8029620 A GB 8029620A GB 8029620 A GB8029620 A GB 8029620A GB 2056988 A GB2056988 A GB 2056988A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/587—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with aliphatic hydrocarbon radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms, said aliphatic radicals being substituted in the alpha-position to the ring by a hetero atom, e.g. with m >= 0, Z being a singly or a doubly bound hetero atom
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- Health & Medical Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cephalosporin Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Abstract
The compounds of the general formula: <IMAGE> (wherein alk is a (C1-C4) alkyl radical) and X is chlorine, bromine or iodine and of the general formula: <IMAGE> (wherein R' is alk or hydrogen) are novel compounds useful as intermediates in the preparation of the anti-bacterial compounds claimed in our co-pending Application No. 30305/78, Serial No. 2,005,660. The compounds A, wherein R' is alk, may be prepared by treating the compounds III' with a strong base, and the latter may themselves be prepared from the corresponding unsubstituted oxime. The derivative A wherein R' is hydrogen may be prepared by treating the derivative A wherein R' is alk with a base and then with an acid.
Description
1 GB 2 056 988 A 1
SPECIFICATION Oxime Derivatives of 2-(2-tritylamino-thiazoiyi)-acetic Acid and Alkyl Esters Thereof
This invention relates to oxime derivatives of 2-(2-tritylaminothiazoiyi)-acetic acid and alkyl esters thereof which are believed to be useful as intermediates in preparation of antibiotic compounds.
Our co-pending Application No. 30305/78 (Serial No. 2,005,660) from which this Application is. 5 divided, describes and claims antibiotic compounds of the general formula:
HN-Ra 1.N 0 H CH 2-0 -C - C H 3 N N --:- i CO2A O4.:--: CH2 0 ( 1 1) wherein R,, represents a hydrogen atom or a trityl group and A represents a hydrogen atom or an alkali metal atom, and equivalent of an alkalineearth metal atom or a magnesium atom, or a substituted 10 ammonium group, the compounds being in the form of the syn or anti isomers. The syn isomers of general formula l' are of the formula:
NH-Ra s-,- N 101 N 0 CH2-0-C- CA 02 0 11 N ",, OCH=CH2 and the anti isomers of general formula l' are of the formula:
H H - R a.
51.N H2C=Ho ""' 0 11 N CH2-0-C-CH-CH3 11 E02A 0 The compounds of general formula l' are also tautomeric about the 2-atom in the thiazolyl ring 15 and adjacent nitrogen atoms. One of the tautomeric structures is as depicted in general formula F. The other tautomeric structure is:
H-Ra N H 0 0 H CH20- C,,-CH3 OCH22CH2 02A N -, 0 2 GB 2 056 988 A 2 The compounds of general formula l' may be prepared, by a process which is fully described in the aforesaid co-pending Application, from an acid of the structural formula:
E 6003 E- H H 5..,- H C 11 1..111 C02H (Ila) N-O-CH C H2 0 Accordingly, this invention provides the acid of formula "a, in the form of a syn or anti isomer. 5 The acid of formula ll,, may be prepared by treating a compound of the general formula:
which acid is believed to be novel.
60S) 3 E - NI C02atk (I1Ib) H- 0 - EH = C H 2 (wherein alk represents an alkyl radical of from 1 to 4 carbon atoms) with a base, and then with an acid, to obtain the desired acid of formula II..
The base with which the compound of formula IN is treated may be a mineral base such as barium oxide or sodium or potassium hydroxide, and the preferred base is potassium hydroxide in a mixture of a cyclic ether such as dioxan and an alcohol such as ethanol. The acid used subsequent to the base may be an organic acid such as formic or acetic acid, although it is preferred to use a dilute mineral acid such as dilute hydrochloric acid.
The compounds of general formula IN are also believed to be novel, and this invention provides 15 them in the form of syn or anti isomers.
The compounds of general formula 111b may be prepared by a process in which a compound of the general formula:
H H - E (E6H513 - 102alk -2 "", 1 1 f 1 1.
H 0 - 1 H 2 - C H 2 X (1111) (wherein alk is as defined above and X represents a chlorine, bromine or iodine atom) is treated with a 20 strong base so as to obtain the desired compound of general formula 111W The strong base with which the compound of general formula Ill' is treated is preferably an alkali metal alkylate such as potassium tert-butylate, in a dialkyl sulphoxide solvent such as dimethyl sulphoxide. The treatment is best performed at ambient temperature.
The compounds of general formula Ill' are themselves believed to be novel, and this invention 25 provides them in the form of syn or anti isomers.
The compounds of general formula Ill' may be prepared by a process in which a compound of general formula X-CI-1,7-CH,-X (wherein X represents a chlorine, bromine or iodine atom) is reacted, in the presence of a base, with a compound of the general formula:
3 GB 2 056 988 A 3 NII-C (C6115h "k N C02alk (va) wherein alk is as defined hereinbefOre, to obtain the desired compound of general formula IIF.
The compound of general formula XCH-CH2X is preferably 1,2-dibromoethane.
The base employed in the reaction may be a tertiary amine such as triethylamine, or an alkali metal alkylate such as potassium tert-butylate, in a polar solvent such as dimethyl formamide or 5 tetrahydrofuran. The preferred base is however an alkali metal carbonate such as potassium carbonate in dimethyl formamide.
The compounds of general formula V. may be prepared by reacting thiourea with a compound of general formula:
CL-CH2-C-1-CO2alk 11 11 0 H 1 (V11a) (wherein alk is as hereinbefore defined) to obtain a compound of general formula.
NH2 C 0 2 alk ON MC) (wherein alk is as hereinbefore defined) which compound is treated with an equivalent amount of trityl chloride to obtain the desired compound of general formula VaIt is mentioned in our aforesaid co-pending Application that the compounds of general formula 1' 15 are preferably syn isomers, and it follows from this that their precursors, the compounds of general formulae II., III' and 111b are also preferably syn isomers. The syn isomers of general formulae "a, 111' and IN may naturally be prepared from the compounds of general formula IVc that are syn isomers by the processes just described. 20 However, specific reaction conditions should preferably be employed in the reaction of thiourea 20 with the compounds of general formula VIIa, if it is desired to prepare the compounds of general formula IVc specifically in the form of syn isomers. These special conditions are that the reaction should take place a) in an aqueous solvent such as aqueous acetone or aqueous ethanol; b) at ambient temperature, using a substantially stoichiometric amount of thiourea and a relatively short reaction time of from one to three hours; orc) using a combination of a) and b).
The following Examples are given, though only by way of illustration, to show some preferred aspects of this invention.
Example 1 Ethyl 2-(2-bromoethoxyimino)-2-(2-tritylamino-4-thiazolyi)acetate, Syn Isomer Stage A Ethyl 2-hydroxyimino-2-(2-amino-4-thiazolyi)-acetate, Syn Isomer 0.8 g of thiourea were dissolved in 2.4 cm1 of ethanol and 4.8 CM3 of water. Over 5 minutes, a solution of 2 g of ethyl 4-chloro-2-hydroxyiminoacetyl-acetate were added and the whole was agitated for one hour at ambient temperature. The major part of the ethanol was driven off under partial vacuum and the pH was brought to 6 by adding solid sodium acid carbonate. After chilling, 4 GB 2 056 988 A 4 vacuum-filtering, washing with water and drying under vacuum at 401C, 1. 32 9 of expected product were obtained. M.N.=2321C.
Analysis: Cr^0^S Calculated: C% 39.06 1-1% 4.21 N% 19.52 S% 14.9 Found: C% 38.9 1-1% 4.4 N% 19.7 S% 14.6 Stage B Ethyl 2-(2-tritylamino-4-thiazoiyi)-2-hydroxyimino-acetate Hydrochloride, Syn Isomer 43.2 g of ethyl 2-(2-amino-4-thiazolyi)-2-hydroxyimino-acetate, syn isomer, prepared as in Stage A above, were introduced into 120 cm3 of dry dimethyl formamide.
The whole was cooled to -35C and 32 em' of triethylamine were introduced, followed over 30 minutes, by 60 9 of trityl chloride in portions. The temperature was allowed to rise again and total dissolution of the solid matter was observed. The solution was then heated to 3WC, and after one hour was poured into 1.2 litres of iced water containing 40 cm3 of 220 M hydrochloric acid.
The whole was agitated in a bath of ice water, and after vacuumfiltration and rinsing with normal hydrochloric acid, the product was made into a paste with ether. 69.3 9 of the hydrochloride were 15 obtained.
Stage C Ethyl 2-(2-bromoethoxyimino)-2-(2-tritylamino-4-thiazoiyi)acetate, Syn Isomer Under argon, at ambient temperature and over 3 minutes, 4.14 g of potassium carbonate were introduced into a mixture of 4.94 g of ethyl 2-hydroxy-irnino-2-(2- tritylamino-4-thiazoiyl)-acetate hydrochloride, syn isomer, prepared as in Stage B above, in 10 CM3 of dimethyl formamide. The whole was agitated for 20 minutes at 201C, after which 8.65 CM3 Of 1,2-dibromoethane were added. After further agitation for 30 hours, the whole was poured into a medium comprising 100 CM3 of distilled water and 20 em' of methylene chloride. After decanting, re-extracting with methylene chloride, washing with distilled water and re-extracting, the organic solutions were dried, vacuum-filtered, rinsed and distilled to dryness. A crude product was obtained which was chromatographed on silica, eluting with benzene containing 5% of ether, to recover a first fraction. This was recrystallised from methanol after dissolution at 50-601C and vacuum- filtration at 0IC-+51'C. 1.16 9 of creamy white product were obtained. M. Pt.=1 171C.
A homogeneous fraction of 1.258 g was then obtained. NIVIR=p.p.m. (C13C1, ) triplet=3.55 J=7 Hz CH2-13r triplet=4.51 J=6 Hz N-O-CH2 singlet=6.55, proton of the thiazole ring.
1 Example 2
Ethyl 2-(2-tritylamino-4-thiazoiyi)-2-vinyloxyimino Acetate, Syn Isomer 6.9 g of ethyl 2-(2-bromoethoxyimino)-2-(2-trityiamino-4-thiazolyl)acetate, syn isomer, prepared as in Example 1, was placed in 35 cm3 of dimethyl sulphoxide. At 20-251C and over 5 minutes, 16 cm3 of a 1 M solution of potassium tert-butylate in tetrahydrofuran were introduced, after which the whole was agitated for 30 minutes before the introduction, at ambient temperature, of a further 3 em' of 1 M solution of potassium tert-butylate in tetrahydofuran. Agitation was continued for 40 a further 30 minutes, and then again 3 CM3 of the same solution of potassium tert-butylate was introduced, followed, after another 30 minutes, by a third 3 CM3 of the solution.
After the last introduction the whole was agitated again for 30 minutes and then poured into a mixture of 350 cm3 of water and ice and 90 CM3 of methylene chloride.
A5 The whole was acidified to pH 2 with 28 CM3 of normal hydrochloric acid, then after decanting and re-extracting with 3 times 50 CM3 of methylene chloride, washing with distilled water, drying, vacuum-filtering and rinsing, the product-containing liquid was distilled to dryness. A black resin was obtained which was purified by chromatography on a column of silica, eluting with methylene chloride, to give 3.227 g of expected product. NMR p.p.m. (CDCI:3) range of peaks from 4.16 to 4.83 p.p.m.=CH2 range of peaks from 6.66 to 7.33 p.p.m.=CH singlet at 6.65-proton of the thiazole ring.
After recrystallisation from absolute ethanol a product was obtained of melting point 1 141C.
Analysis: (C2,H2,03N3S) Example 3
2-(2-tritylamino-4-thiazoiyl)-2-vinyloxyimino Acetic Acid, Syn Isomer 3.227 9 of ethyl 2-(2-tritylamino-4-thiazolyi)-2vinyi-oxyimino-acetate, syn isomer, prepared in Example 2 was placed in 3.2 CM3 of dioxan. At ambient temperature, 20 em' of a 0.5M solution of 60 Calculated:C% 69.54 1-1% 5.21 N% 8.69 S% 6.36 Found: C% 69.2 H% 5.2 N% 8.3S% 6.6 If GB 2 056 988 A potassium hydroxide in absolute ethanol were added, followed by 12 cml of absolutq ethanol. Under argon, the whole was brought to 501C with agitation and maintained there for 1 hour; the potassium salt then crystallised out. The temperature was lowered to 200C, and after vacuumfiltration and rinsing with ethanol, the product was taken up with a mixture of 50 cml of ethyl acetate and 50 CM3 Of distilled water.
The taken-up product was acidified using 6 GM3 of 2N hydrochloric acid, and the whole was agitated until two homogeneous phases were obtained. After decanting, washing with three times 20 cm 3 of distilled water, reextracting with ethyl acetate, drying and vacuum-filtering, the resultant product-containing liquor was rinsed with ethyl acetate, concentrated to 15 CM3, chilled to 01C- +511C, vacuum-filtered and rinsed with ethyl acetate. The solid was dried to give 2.53 g of the expected 10 product, which after recrystallisation had a melting point of 1 501C.
In the following claims, all formulae and substituents therein are, unless otherwise indicated, as first defined.
Claims (19)
1. The acid of the structural formula (C 6 H03 C- H H in the form of a syn or anti isomer.
C02H N-O-CH =CH2 Ma)
2. A process for preparing the acid of structural formula lla, in which process a compound of the general formula (6H5)3E-HN C02alk N ' 0 - C H --- C H 2 ( Mb) (wherein alk represents an alkyf radical of from 1 to 4 carbon atoms) is treated with a base, and then with an acid, to obtain the desired acid of formula Ila.
3. A process as claimed in claim 2, in which the treatment with a base is carried out with potassium hydroxide in a mixture of dioxan and ethanol.
4. A process as claimed in claim 2 or claim 3, in which the treatment with an acid is carried out 25 with hydrochloric acid.
5. A process for preparing the acid of formula Ila, substantially as hereinbefore described with reference to Example 3.
6. The compounds of the general formula 11 lb in the form of syn or anti isomers.
7. A process for preparing the compounds of general formula Illb, in which process a compound 30 of the general formula:
N H - C (C6H513 C02alk N.1, 0 - C H 2 - C H 2 X (1111) (wherein X represents a chlorine, bromine or iodine atom) is treated with a strong base so as to obtain the desired compound of general formula 111b GB 2 056 988 A 6
8. A process as claimed in claim 7, in which the strong base is an alkali- metal alkylate in dimethyl sulphoxide.
9. A process for preparing the compounds of general formula Ill' substantially as hereinbefore described with reference to Example 2.
10. A process as claimed in any of claims 2 to 4, in which the compounds of general formula Illb 5 is prepared by a process as claimed in claim 7 or claim 8.
11. The compounds of general formula lIV, in the form of syn or anti isomers.
12. A process for preparing the compounds of general formula JIV, in which process a compound of general formula X-CH,7-CHi----X is reacted, in the presence of a base, with a compound of the generalformula:
to obtain the desired compound of general formula 11P.
H-C (C6H5)3 5"kN C 0 2 ?' 1 k H -"", 0 H (Va)
13. A process as claimed in claim 12, in which the compound of general formula)(CH27--CH2X'S 1,2-dibromoethane.
14. A process as claimed in claim 12 or claim 13, in which the base is an alkali metal carbonate 15 in dimethyl formamide.
15. A process as claimed in any of claims 12 to 15, in which the compound of general formula is prepared by reacting thiourea with a compound of general formula:
C I-CH2- E- C -CO 2 at k 11 11 0 H 'I- OH to obtain a compound of general formula:
Va (V11a) 511.N N OH MC) which compound is treated with an equivalent amount of trityl chloride to obtain the desired compound of general formula V..
16. A process as claimed in claim 15, in which the reaction between thiourea and the compound of general formula VII, takes place a) in an aqueous solvent; b) at ambient temperature, using a 25 substantially stoichiometric amount of thiourea and a reaction time of from one to three hours; or c) using a combination of a) and b).
17. A process for preparing a compound of general formula Ill', substantially as hereinbefore described with reference to Example 1.
18. A process as claimed in any of claims 7, 8 or 10, in which the compound of general formula 30 IIV is prepared by a process claimed in any one of claims 12 to 16.
19. A compound as claimed in any of claims 1, 6 or 11 in the form of a syn isomer.
New Claims or Amendments to Claims filed on 22nd December 1980. Superseded Claims 9 and 15.
New or Amended Claims:- 9. A process for preparing the compounds of general formula 111b substantially as hereinbefore described with reference to Example 2.
1 7 GB 2 056 988 A 7 15. A process as claimed in any of claims 12 to 14, in which the compound of general formula Va is prepared by reacting thiourea with a compound of general formula:
E L-CH2- [,,-,C, -C02 a[ k 0 N (V11a) to obtain a compound of general formula:
NH2 5 "-'jN ú02alk ON MC) which compound is treated with an equivalent amount of trityl chloride to obtain the desired compound of general formula Va.
Printed for Her Majesty's Stationery Office by the Courier Press, Leamington Spa, 1981. Published by the Patent Office, 25 Southampton Buildings. London, WC2A 1 AY, from which copies may be obtained.
1
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7722077A FR2408613A2 (en) | 1977-07-19 | 1977-07-19 | NEW OXIMES DERIVED FROM 7-AMINO THIAZOLYL ACETAMIDO CEPHALOSPORANIC ACID, THEIR PREPARATION PROCESS AND THEIR APPLICATION AS MEDICINAL PRODUCTS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB2056988A true GB2056988A (en) | 1981-03-25 |
| GB2056988B GB2056988B (en) | 1982-11-17 |
Family
ID=9193491
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8029620A Expired GB2056988B (en) | 1977-07-19 | 1978-07-19 | Oxime derivatives of 2 - (2 - tritylamino-thiazolyl) - acetic acid and alkyl esters thereof |
| GB7830305A Expired GB2005660B (en) | 1977-07-19 | 1978-07-19 | Oxime derivatives of 7-amino-thiazolyl-acetamido-cephalosporanic acid |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB7830305A Expired GB2005660B (en) | 1977-07-19 | 1978-07-19 | Oxime derivatives of 7-amino-thiazolyl-acetamido-cephalosporanic acid |
Country Status (16)
| Country | Link |
|---|---|
| JP (1) | JPS5422392A (en) |
| AT (1) | AT359644B (en) |
| AU (1) | AU527621B2 (en) |
| BE (1) | BE869079R (en) |
| CA (1) | CA1123824A (en) |
| CH (1) | CH632503A5 (en) |
| DE (1) | DE2831332A1 (en) |
| DK (1) | DK162094C (en) |
| ES (2) | ES471647A2 (en) |
| FR (1) | FR2408613A2 (en) |
| GB (2) | GB2056988B (en) |
| IE (1) | IE47335B1 (en) |
| IT (1) | IT1156871B (en) |
| LU (1) | LU79998A1 (en) |
| NL (1) | NL7807741A (en) |
| SE (1) | SE7807274L (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2399418A1 (en) * | 1977-03-14 | 1979-03-02 | Fujisawa Pharmaceutical Co | Heterocyclyl-imino-acetamido-cephalosporin derivs. |
| PH17188A (en) * | 1977-03-14 | 1984-06-14 | Fujisawa Pharmaceutical Co | New cephem and cepham compounds and their pharmaceutical compositions and method of use |
| FR2476647A2 (en) * | 1980-02-26 | 1981-08-28 | Roussel Uclaf | 7-Amino-thiazolyl-acetamido-cephalosporin oxime derivs. - are broad spectrum antibacterials useful against penicillin resistant Staphylococci (BE 25.9.78) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2346014A1 (en) * | 1976-01-23 | 1977-10-28 | Roussel Uclaf | Amino-thiazolyl-hydroxyimino-acetamido-cephalosporanic acids - with antibacterial activity |
| SE440655B (en) * | 1976-01-23 | 1985-08-12 | Roussel Uclaf | SET TO MAKE NEW OXIME DERIVATIVES OF 7-AMINO-THIAZOLYL-ACETAMIDO-CEPHALOSPORANIC ACID |
-
1977
- 1977-07-19 FR FR7722077A patent/FR2408613A2/en active Granted
-
1978
- 1978-06-27 SE SE787807274A patent/SE7807274L/en unknown
- 1978-07-12 JP JP8410078A patent/JPS5422392A/en active Granted
- 1978-07-12 ES ES471647A patent/ES471647A2/en not_active Expired
- 1978-07-17 DE DE19782831332 patent/DE2831332A1/en not_active Ceased
- 1978-07-18 LU LU79998A patent/LU79998A1/en unknown
- 1978-07-18 CH CH773178A patent/CH632503A5/en not_active IP Right Cessation
- 1978-07-18 BE BE189345A patent/BE869079R/en not_active IP Right Cessation
- 1978-07-18 DK DK320578A patent/DK162094C/en not_active IP Right Cessation
- 1978-07-18 AU AU38133/78A patent/AU527621B2/en not_active Expired
- 1978-07-18 IT IT50356/78A patent/IT1156871B/en active
- 1978-07-19 GB GB8029620A patent/GB2056988B/en not_active Expired
- 1978-07-19 GB GB7830305A patent/GB2005660B/en not_active Expired
- 1978-07-19 CA CA307,727A patent/CA1123824A/en not_active Expired
- 1978-07-19 AT AT522878A patent/AT359644B/en not_active IP Right Cessation
- 1978-07-19 IE IE1450/78A patent/IE47335B1/en not_active IP Right Cessation
- 1978-07-19 NL NL7807741A patent/NL7807741A/en not_active Application Discontinuation
-
1979
- 1979-03-28 ES ES479027A patent/ES479027A1/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| GB2056988B (en) | 1982-11-17 |
| JPS5422392A (en) | 1979-02-20 |
| IE47335B1 (en) | 1984-02-22 |
| AU3813378A (en) | 1980-01-24 |
| NL7807741A (en) | 1979-01-23 |
| BE869079R (en) | 1979-01-18 |
| AU527621B2 (en) | 1983-03-17 |
| IE781450L (en) | 1979-01-19 |
| GB2005660B (en) | 1982-03-10 |
| DE2831332A1 (en) | 1979-02-08 |
| DK320578A (en) | 1979-01-20 |
| LU79998A1 (en) | 1979-04-09 |
| DK162094B (en) | 1991-09-16 |
| JPS6259708B2 (en) | 1987-12-12 |
| ES479027A1 (en) | 1979-07-01 |
| FR2408613A2 (en) | 1979-06-08 |
| GB2005660A (en) | 1979-04-25 |
| FR2408613B2 (en) | 1980-04-18 |
| CA1123824A (en) | 1982-05-18 |
| DK162094C (en) | 1992-02-17 |
| SE7807274L (en) | 1979-01-20 |
| ATA522878A (en) | 1980-04-15 |
| IT7850356A0 (en) | 1978-07-18 |
| IT1156871B (en) | 1987-02-04 |
| AT359644B (en) | 1980-11-25 |
| CH632503A5 (en) | 1982-10-15 |
| ES471647A2 (en) | 1979-10-16 |
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| PE20 | Patent expired after termination of 20 years |
Effective date: 19980718 |