EP0434731A1 - Procede permettant de preparer des composes oxazolins - Google Patents

Procede permettant de preparer des composes oxazolins

Info

Publication number
EP0434731A1
EP0434731A1 EP89910484A EP89910484A EP0434731A1 EP 0434731 A1 EP0434731 A1 EP 0434731A1 EP 89910484 A EP89910484 A EP 89910484A EP 89910484 A EP89910484 A EP 89910484A EP 0434731 A1 EP0434731 A1 EP 0434731A1
Authority
EP
European Patent Office
Prior art keywords
substituted
carbon atoms
alkyl
moiety
aryl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP89910484A
Other languages
German (de)
English (en)
Inventor
Doris P. Schumacher
Jon E. Clark
Bruce L. Murphy
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Sharp and Dohme Corp
Original Assignee
Schering Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Schering Corp filed Critical Schering Corp
Publication of EP0434731A1 publication Critical patent/EP0434731A1/fr
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/10—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D263/14—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/10—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D263/12—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with radicals containing only hydrogen and carbon atoms

Definitions

  • the present invention is directed to a novel process for preparing oxazoline compounds.
  • Oxazoline compounds are useful in preparing surface active agents, detergents, waxes, and intermediates for pharmaceutical compounds, such as those disclosed in U.S. Patent 4,743,700.
  • Patent 2,759,001 discloses preparing racemic mixtures of isomeric oxazolines by reacting dichloroacetonitrile with an aminodiol compound.
  • U.S. Patent 3,979,405 discloses preparing 2- oxazolines by reacting an a ino alcohol with a nitrile in an anhydrous alcohol such as n-butanol or cyclohexanol. None of these references teach a method for preparing oxazolines employing a dihydric or polyhydric alcohol solvent. It would be desirable to provide a process for preparing oxazoline compounds whose yields, purity and selectivity are as good as or better than methods previously taught.
  • the present invention is directed toward a process for preparing oxazoline compounds of the formula:
  • R 1 , R 2 , R 3 , R 4 and R 5 can be the same or different, each independently represents hydrogen, alkyl, haloalkyl, cycloalkyl or substituted cycloalkyl, cycloalkalkyl or substituted cycloalkalkyl, alkenyl or substituted alkenyl, alkynyl, alkenylalkyl or substituted alkenylalkyl, alkynylalkyl, alkoxyalkyl or substituted alkoxyalkyl, dialkylamino- alkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, arylalkenyl or substituted arylalkenyl, alkoxyaryl or substituted alkoxyaryl, aryloxyaryl or substituted aryloxyaryl, aryloxyalkyl or substituted aryloxyalkyl, acyl or substituted acyl, aromatic heterocyclic or substitute
  • the process comprises the step of contacting a cyano compound of the formula
  • R 1 , R 2 , R 3 , R 4 and R 5 are as defined hereinbefore, performed in the presence of a base and a dihydric alcohol solvent, a polyhydric alcohol solvent or mixture thereof.
  • R 1 and R 2 independently represent hydrogen, sulfide, sulfoxide, sulfonyl, aryl or substituted aryl
  • R and R 4 independently represent hydrogen, alkyl or hydroxyalkyl
  • R 5 is phenyl, 4-nitrophenyl, cinna yl, 4-methoxy- cinnamyl or dichloromethyl.
  • R 2 is 4- methylthiopheny1, 4-methyl-SO-phenyl or 4-methyl-S0 2 - phenyl; R 4 is hydroxy ethyl and R 5 is phenyl or dichloromethyl when R 1 and R 3 are hydrogen.
  • the base is diazabicycloundecene, more specifically 1,8- diazobicyclo[5.4.0]undec-7-ene (DBU) or an alkali metal carbonate, most preferably potassium carbonate.
  • DBU 1,8- diazobicyclo[5.4.0]undec-7-ene
  • the alcohol solvent is a mixture of a dihydric alcohol and a polyhydric alcohol, most preferably a mixture of ethylene glycol and glycerol.
  • R 1 and R 2 are as defined hereinabove.
  • the process is regio-selective. That is, although the reaction potentially can give rise to two or more structural isomers, the present process produces only one of the two or more potential structural isomers.
  • the process has the advantages of being able to prepare an oxazoline compound of formula (X) in high yields, good purity, high specificity, with low by ⁇ product formation using relatively mild reaction conditions with as few or fewer steps than other processes previously taught.
  • the present invention has the further advantage of providing a process of preparing oxazoline compounds as economically, if not more so, than other processes previously taught.
  • the present invention has the further advantage of providing a process for preparing oxazoline compounds whose stereoisomeric configuration can be easily determined aforehand simply by the selection of the appropriate starting materials.
  • An especially advantageous feature of the present invention is that virtually no racemization occurs when chiral starting material of formula IX are used. In the particular situation where the a ino alcohol starting material contains two hydroxyl groups, the present process has the advantage in that it is regio-selective.
  • alkyl refers to a straight saturated hydrocarbon moiety (i.e. hydrocarbons having carbon- carbon single bonds) containing from 1 to 6 carbon atoms, or a branched saturated hydrocarbon moiety of 3 to 6 carbon atoms, such as for example, methyl (i.e. -CH 3 ) , ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl and the like; the term “substituted alkyl” refer to an alkyl moiety which if further substituted at the carbon by one or more of the following groups: halo, alkyl of one to.
  • halogen and halo refers to fluoride, chloride, bromide or iodide.
  • haloalkyl refers to an alkyl moiety in which one or more of the hydrogen atoms has been replaced by a halogen atom, such as, for example, chloromethyl, fluoromethyl, bromomethyl, trifluoromethyl, dichloromethyl, 2-chloro-2-fluoroethyl, 6,6,6- trichlorohexyl and the like.
  • cycloalkyl refers to a saturated carbocyclic ring characterized by closed rings and containing from 3 to 6 carbon atoms, such as for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like;
  • substituted cycloalkyl refers to a cycloalkyl moiety which is further substituted at the carbon by one or more of the following groups: halo, alkyl of one to six carbon atoms, aryl of six to fifteen carbon atoms, cyano, carboxyl, or salts thereof, nitro and hydroxyl;
  • cycloalkalkyl refers to a cycloalkyl moiety of 3 to 6 carbon atoms covalently bonded to an alkyl moiety of 1 to 6 carbon atoms;
  • substituted “cycloalkalkyl” refer to a cycloalkalkyl moiety which is further substituted at the carbon by one or more of the following groups: halo, alkyl of one to six carbon atoms, aryl of six to fifteen carbon atoms, cyano (i.e. -CN) , carboxyl (i.e. -COOH) or salts thereof, nitro (i.e. -N0 2 ) and hydroxyl;
  • alkenyl refers to a straight hydrocarbon moiety of two to six carbon atoms or a branched hydrocarbon moiety of three to six carbon atoms having at least one carbon-carbon double bond, such as ethenyl (i.e.
  • substituted alkenyl refers to an alkenyl moiety which is further substituted at a substitutable carbon by one or more of the following groups: halo, alkyl of one to six carbon atoms, aryl of six to fifteen carbon atoms, cyano, carboxyl or salts thereof, nitro and hydroxyl;
  • alkynyl refers to a straight hydrocarbon moiety of two to six carbon atoms or a branched hydrocarbon moiety of four to six carbon atoms having one carbon to carbon triple bond such as ethynyl (i.e.
  • alkynyl refers to an alkynyl moiety which is further substituted at a substitutable carbon by one or more of the following groups: halo, alkyl of on to six carbon atoms, aryl of six to fifteen carbon atoms, cyano, carboxyl or salts thereof, nitro and hydroxyl;
  • alkoxy refers to an alkyl moiety containing from 1 to 6 carbon atoms covalently bonded to an adjacent structural element through an oxygen atom, such as for example, methoxy (i.e.
  • substituted alkoxy refers to an alkoxy moiety which is further substituted at the carbon by one or more of the following groups: halo, alkyl of one to six carbon atoms, aryl of six to fifteen carbon atoms, cyano, carboxyl or salts thereof, nitro and hydroxyl;
  • alkenylalkyl refers to an alkenyl moiety of two to six carbon atoms covalently bonded to a alkyl moiety of 1 to 6 carbon atoms;
  • substituted alkenylalkyl refers to an alkenylalkyl moiety which is further substituted at a carbon by one or more of the following groups: halo, alkyl of one to six carbon atoms, aryl of six to fifteen carbon atoms, cyano, carboxyl or salts thereof, nitro and hydroxyl;
  • amino refers to a primary (-NH 2 ) , a secondary or a tertiary amine wherein each hydrogen can be substituted by an alkyl moiety of one to six carbon atoms or by an aryl moiety of six to fifteen carbon atoms.
  • aryl refers to a carbocyclic moiety containing at least one benzenoid-type ring, with the aryl groups preferably containing from 6 to 15 carbon atoms, for example, phenyl, naphthyl, indenyl, indanyl, and the like; the term “substituted aryl” refers to an aryl moiety which is further substituted at the carbon by one or more of the following groups: halo, alkyl of one to six carbon atoms, aryl of six to fifteen carbon atoms, cyano, carboxyl or salts thereof, nitro and hydroxyl;
  • arylalkyl refers to an aryl moiety of 6 to 15 carbon atoms covalently bonded to an alkyl moiety of one to six carbon atoms such as, for example, benzyl, phenylethyl, and the like;
  • substituted aralkyl refers to an aralkyl moiety which is further substituted at the carbon by one or more of the following groups: halo, alkyl of one to six carbon atoms, aryl of six to fifteen carbon atms, cyano, carboxyl or salts thereof, nitro and hydroxyl;
  • arylalkenyl refers to an aryl moiety of six to fifteen carbon atoms covalently bonded to an alkenyl moiety of two to six carbon atoms, such as, for example, 2-phenyl-l-ethenyl (cinnamyl) , 4-phenyl-2- butenyl and the like;
  • substituted arylalkenyl refers to an arylalkenyl moiety which is further substituted at the carbon by one or more of the following groups: halo, alkyl of one to six carbon atoms, aryl of six to fifteen carbon atoms, cyano, carboxyl or salts thereof, nitro and hydroxyl;
  • aryloxyalkyl refers to an aryloxy moiety as defined hereinbefore covalently bonded to an alkyl moiety of one to six carbon atoms, such as, for example, phenoxymethyl, 1-naphthyloxyethyl and the like;
  • substituted aralkyl refers to an arakyl moiety which is further substituted at the carbon by one or more of the following groups: halo, alkyl of one to six carbon atoms, aryl of six to fifteen carbon atoms, cyano, carboxyl or salts thereof, nitro and hydroxyl;
  • acyl refers to a carbonyl moiety
  • alkanoyl moiety (alkyl-nC-) of one to sxx carbon atoms in
  • alkoxy-C- of one to six carbon atoms in the alkoxy
  • acyl groups include acetyl, benzoyl, ethoxycarbonyl and the like; the term "substituted acyl" refers to the akyl, aryl, alkoxy, amino, aryloxy, alkanoyl, aroyl, ester, amide or aryloxy portion of the acyl moiety which is further substituted at a carbon by one or more of the following groups: halo, alkyl of one to six carbon atoms, aryl of six to fifteen carbon atoms, cyano, carboxyl or salts thereof, nitro and hydroxyl;
  • aromatic heterocyclic refers to a cyclic moiety having at least one O, S and/or N hetero ⁇ atom interrupting the ring structure and having a sufficient number of unsaturated carbon to carbon double bonds, nitrogen to carbon double bonds, and the like, to provide aromatic character, with the aromatic heterocyclic groups preferably containing from 2 to 14 carbon atoms, for example, 2-, 3- or 4-pyridyl, 2- or 3- furyl, 2- or 3-thienyl, 2-, 4- or 5-thiazolyl, 2-, 4- or 5-imidazolyl, 2-, 4- or 5-pyrimidinyl, 2-pyrazinyl, 3- or 4-pyridazinyl, 3-, 5- or 6-[l,2,4-triazinyl] , 3- or 5- [1,2,4-thiadiazolyl] , 2-, 3-, 4-, 5-, 6- or 7- benzofuranyl, 2-, 3-, 4-, 5-, 6- or 7-indolyl, 3-, 4- or 5-pyrazolyl, 2-, 4- or
  • heterocyclic alkyl refers to an aromatic heterocyclic moiety of 2 to 14 carbon atoms as defined hereinbefore, covalently bonded to an alkyl moiety of one to six carbon atoms;
  • substituted heterocyclic alkyl refers to a heterocyclic alkyl moiety which is further substituted at a carbon or heteroatom by one or more of the following groups: halo, alkyl of one to six carbon atoms, aryl of six to fifteen carbon atoms, cyano or salts thereof, nitro and hydroxyl;
  • heterocyclic cycloalkyl refers to a saturated carbocyclic ring of two to six carbon atoms having at least one oxygen, sulfur or nitrogen atom, or combination thereof, interrupting the ring structure, and are substituted at a carbon atom, such as 2-, 3-, or 4- piperidyl, 2-dioxanyl, 2- or 3-oxazetidinyl, 2-oxiran
  • heterocyclic cycloalkylalkyl refers to a heterocyclic cycloalkyl moiety of two to six carbon atoms covalently bonded to an alkyl moiety of one to six carbon atoms;
  • substituted cycloalkalkyl refers to a cycloalkalkyl moiety which is further substituted at the carbon by one or more of the following groups: halo, alkyl of one to six carbon atoms, aryl of six to fifteen carbon atoms, cyano, carboxyl or salts thereof, nitro and hydroxyl;
  • sulfonyl refers to a sulfonyl moiety (i.e. R-S0 2 -R-) wherein each R independently represents alkyl of one to six carbon atoms or aryl of six to twelve carbon atoms, such as, for example, CH 3 -S0 2 ⁇ ° / ⁇ ' the term “substituted sulfonyl” refers to a sulfonyl moiety as defined above whose "R” group is further substituted at the carbon by one or more of the following groups: halo, alkyl of one to six carbon atoms, aryl of six to fifteen carbon atoms, cyano, carboxyl or salts thereof, nitro and hydroxyl;
  • substituted sulfide refers to a sulfide moiety as defined above whose "R” group is further substituted at the carbon by one or more of the following groups: halo, alkyl of ne to six carbon atoms, aryl of six to fifteen carbon atoms, cyano, carboxyl or salts thereof, nitro and hydroxyl;
  • the base employed in the present process is any substance which will remove a proton from the hydroxyl (-OH) of the moiety
  • Bases which can be employed in process of the present invention can be a non-aqueous base such as lithium diisopropyl amide, lithium hexamethylsilazide, sodium hexamethylsilazide and potassium hexamethylsilazide; or potassium t-butoxide and sodium methoxide.
  • the base can be an alkali metal carbonate such as sodium, potassium, lithium or cesium carbonate or an alkaline earth metal carbonate such as calcium or barium carbonate; hydroxides such as sodium and potassium hydroxides; and hydrides such as sodium or potassium hydrides.
  • alkali metal carbonate such as sodium, potassium, lithium or cesium carbonate
  • alkaline earth metal carbonate such as calcium or barium carbonate
  • hydroxides such as sodium and potassium hydroxides
  • hydrides such as sodium or potassium hydrides.
  • the base can also be ammonia (NH 3 ) or an organic base including urea; a secondary a ine such as dimethylamine, diphenylamine, N-methyl N-propylamine, diethylamine, diisopropylamine, N-methylaniline, piperazine, piperidine, pyrrolidme; or a tertiary amine such as trimethylamine, dimethylaniline, N,N- dimethylpropylamine, N,N-dimethylpiperidine, N,N- dimethylbutylamine, triethylamine.
  • a secondary a ine such as dimethylamine, diphenylamine, N-methyl N-propylamine, diethylamine, diisopropylamine, N-methylaniline, piperazine, piperidine, pyrrolidme
  • a tertiary amine such as trimethylamine, dimethylaniline, N,N- dimethylpropylamine, N,N-dimethylpiper
  • the base is used in amounts effective to remove the requisite proton from the hydroxy moiety.
  • Such amounts in terms of mole ratios can range from about 1,000 to 0.001:1, preferably from about 10 to 0.01:1, more preferably from about 1 to 0.1:1, most preferably about 0.15:1.
  • the alcohol solvent employed in the present invention is preferably dihydric (two OH groups-diol ⁇ ) such as C-2 to C-10 glycols and derivatives.
  • C-2 to C-10 glycols and derivatives include ethylene glycol, propylene glycol, 1,2-butanediol, 1,4- butanediol, pentanediols and the like, more preferably ethylene glycol.
  • the alcohol solvent employed in the present invention is also preferably polyhydric (three or more OH groups-polyols) .
  • Representative polyhydric alcohols include glycerol (1,2,3-propanetriol) , 1,2,4-butanetriol, penta-erythritol and the like, more preferably glycerol.
  • the process of the present invention can employ a mixture of a dihydric and a polyhydric alcohol, most preferably ethylene glycol and glycerol in a volume ratio of 1:2 (ethylene glycol:glycerol) .
  • the alcohol solvent employed in the present process can be used in amounts which can range from an amount sufficient to at least partially solubilize one or both of the reactants and/or the desired product to an amount in excess of either starting reactant.
  • the amount of alcohol solvent can range from about 1 to 5,000 percent or more by weight of an individual reactant, preferably from about 100 to 1,000 percent by- weight, most preferably from about 100 to about 300 percent.
  • the cyano compound (VIII) is contacted with the aminoalcohol (IX) in amounts and under conditions effective to yield the desired oxazoline compound of formula (X) .
  • the cyano compound (VIII) is contacted with the aminoalcohol (IX) at temperatures ranging from about -10 to about 200 degrees Centigrade (°C), preferably from about 70 to about 150°C, most preferably from about 100 to about 110°C.
  • the contacting is performed at ambient pressures although pressures greater or less than ambient can be employed.
  • the contacting of the reactants can be carried out for about 5 minutes to about 72 hours or more until the reaction is substantially completed, preferably from about 1 hour (hr) to about 48 hours. Also preferred is that the reactants are stirred during the contacting procedures.
  • the cyano compound (VIII) can be contacted with the amino alcohol of (IX) in molar ratios ranging from about 100 to 0.1:1; (moles cyano compound (VIII): mole amino alcohol (IX)), preferably from about 10 to 1:1, most preferably from about 2 to 1:1.
  • the stereochemistry of the oxazoline compounds (X) is preserved with respect to the stereochemistry of the starting materials.
  • the resultant oxazoline (X) has a S,S' stereoisomeric configuration.
  • the desired oxazoline compound (X) can be recovered by conventional separatory and recovery methods such as phase separation, distillation or evaporation of any solvents present, crystallization, chromatography, filtration and the like.
  • the reaction mixture can be diluted with water and the oxazoline compound (X) is recovered by filtration.
  • the cyano compounds (VIII) are known and can be prepared by conventional procedures, such as for example, by dehydration of the corresponding amide with a dehydrating agent such as phosphorous oxychloride.
  • the dehydration reaction is illustrated as follows:
  • aminoalcohol compounds (IX) are known and can be prepared by conventional procedures, such as, for example by epoxidation of the corresponding olefin (V) by an epoxidizing method, followed by cleavage of the epoxide ring (VI) by azide to give the azido compound (VII) , followed by reduction of the azido compound with a reducing agent to give the requisite aminoalcohol (IX) .
  • epoxidizing methods include any suitable peracid reactant such as, for example, pertrifluoro- acetic acid (CF 3 COOH ) , perbenzoic acid (C g H 5 COOH ) , peracetic acid (CH 3 COOH ) and the like, as well as formation of a halohydrin followed by base.
  • CF 3 COOH pertrifluoro- acetic acid
  • C g H 5 COOH perbenzoic acid
  • CH 3 COOH peracetic acid
  • any of R 1 , R 2 , R 3 or R 4 of olefin compound (V) contains an oxidizable functionality, such as an unsaturated bond
  • the olefin compound (V) can be selectively epoxidized and/or the requisite epoxide ring compound (VI) thus prepared can be further isolated in order to prepare the azido compound (VII) .
  • Representative azides include those of alkali earth metals, such as sodium azide, potassium azide, lithium azide, and the like.
  • reducing agent refers to any substance which will furnish electrons by its capacity to lose electrons easily, in order to cause the azido compound (VII) receiving the electrons to be reduced to the desired amino alcohol (IX) .
  • reducing agents include, but are not limited to hydrogenating agents and to metal hydrides, such as lithium aluminum hydride (LiAlH 4 ) .
  • hydroxide is intended to include the requisite hydrogenating catalyst(s) and hydrogen (H 2 ) source for reducing the azido compound (VII) to the aminoalcohol (IX) .
  • H 2 hydrogen
  • the hydrogenating catalyst can be nickel, palladium, platinum, platinum oxide, platinum on carbon, and mixture thereof.
  • azido compound (VII) contains a reducible functionality such as an unsaturated bond or a sulfur atom
  • azido compound (VII) can be reduced with a selective reducing agent and/or the requisite amino alcohol (IX) thus prepared can be further isolated in order to prepare oxazoline compound (X) .
  • Salts of the aminoalcohol (IX) can be prepared by contacting the aminoalcohol (IX) with organic or inorganic acids.
  • organic acids include but are not limited to oxalic, tartaric, acetic, trifluoroacetic, citric, maleic and the like.
  • Representative inorganic acids include hydrochloric, sulfuric or phosphoric acids in about equimolar amounts or in amounts less than equimolar of the acid relative to the aminoalcohol.

Abstract

Procédé nouveau de préparation de composés oxazolins comprenant un alcool amino, un composé cyano, une base et un solvant d'alcool dihydrique, un solvant d'alcool polyhydrique ou des mélanges de ceux-ci.
EP89910484A 1988-09-14 1989-09-12 Procede permettant de preparer des composes oxazolins Pending EP0434731A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US24412688A 1988-09-14 1988-09-14
US244126 1988-09-14

Publications (1)

Publication Number Publication Date
EP0434731A1 true EP0434731A1 (fr) 1991-07-03

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Family Applications (2)

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EP89910484A Pending EP0434731A1 (fr) 1988-09-14 1989-09-12 Procede permettant de preparer des composes oxazolins
EP89309235A Expired - Lifetime EP0359516B1 (fr) 1988-09-14 1989-09-12 Procédé de préparation d'oxazolines

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP89309235A Expired - Lifetime EP0359516B1 (fr) 1988-09-14 1989-09-12 Procédé de préparation d'oxazolines

Country Status (12)

Country Link
EP (2) EP0434731A1 (fr)
JP (1) JPH0670022B2 (fr)
AT (1) ATE109775T1 (fr)
CY (1) CY1834A (fr)
DE (1) DE68917394T2 (fr)
ES (1) ES2057137T3 (fr)
FI (1) FI94635C (fr)
HK (1) HK62295A (fr)
HU (1) HU215919B (fr)
NO (1) NO180633C (fr)
SG (1) SG25995G (fr)
WO (1) WO1990002738A1 (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5227494A (en) * 1988-09-14 1993-07-13 Schering Corporation Process for preparing oxazoline compounds
AU646910B2 (en) * 1990-10-25 1994-03-10 Schering Corporation Process for preparing florfenicol, its analogs and oxazoline intermediates thereto
US5973160A (en) * 1992-12-23 1999-10-26 Poss; Michael A. Methods for the preparation of novel sidechain-bearing taxanes
CA2170661A1 (fr) 1995-03-22 1996-09-23 John K. Thottathil Methodes pour la preparation de taxanes a l'aide d'oxazolidines comme produits intermediaires
US6228868B1 (en) 1998-07-27 2001-05-08 Abbott Laboratories Oxazoline antiproliferative agents
MXPA03002494A (es) 2000-09-22 2004-05-24 Bristol Myers Squibb Co Metodo para reducir toxicidad de quimio terapias combinadas.

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2402198A (en) * 1944-09-06 1946-06-18 Du Pont Preparation of oxazolines
HU167760B (fr) * 1972-10-20 1975-12-25
DE3310905A1 (de) * 1983-03-25 1984-09-27 Henkel KGaA, 4000 Düsseldorf Verfahren zur herstellung von 2-isopropenyloxazolinen

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9002738A1 *

Also Published As

Publication number Publication date
JPH0670022B2 (ja) 1994-09-07
SG25995G (en) 1995-08-18
NO180633C (no) 1997-05-21
HU895577D0 (en) 1991-06-28
HUT56083A (en) 1991-07-29
NO910911L (no) 1991-03-07
NO180633B (no) 1997-02-10
HK62295A (en) 1995-05-05
EP0359516B1 (fr) 1994-08-10
WO1990002738A1 (fr) 1990-03-22
JPH03504726A (ja) 1991-10-17
NO910911D0 (no) 1991-03-07
AU4311489A (en) 1990-04-02
FI94635B (fi) 1995-06-30
HU215919B (hu) 1999-03-29
AU617542B2 (en) 1991-11-28
DE68917394T2 (de) 1994-12-01
FI911237A0 (fi) 1991-03-13
CY1834A (en) 1996-09-27
FI94635C (fi) 1995-10-10
DE68917394D1 (de) 1994-09-15
ATE109775T1 (de) 1994-08-15
EP0359516A1 (fr) 1990-03-21
ES2057137T3 (es) 1994-10-16

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