US20070088160A1 - Process for the manufacturing of betamimetics - Google Patents

Process for the manufacturing of betamimetics Download PDF

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Publication number
US20070088160A1
US20070088160A1 US11/463,703 US46370306A US2007088160A1 US 20070088160 A1 US20070088160 A1 US 20070088160A1 US 46370306 A US46370306 A US 46370306A US 2007088160 A1 US2007088160 A1 US 2007088160A1
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Prior art keywords
compound
formula
alkyl
denotes
reacting
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US11/463,703
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Inventor
Thomas Krueger
Uwe Ries
Juergen Schnaubelt
Werner Rall
Zeno Leuter
Adil Duran
Rainer Soyka
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Boehringer Ingelheim International GmbH
Original Assignee
Thomas Krueger
Uwe Ries
Juergen Schnaubelt
Werner Rall
Leuter Zeno A
Adil Duran
Rainer Soyka
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Application filed by Thomas Krueger, Uwe Ries, Juergen Schnaubelt, Werner Rall, Leuter Zeno A, Adil Duran, Rainer Soyka filed Critical Thomas Krueger
Publication of US20070088160A1 publication Critical patent/US20070088160A1/en
Priority to US13/021,946 priority Critical patent/US8420809B2/en
Assigned to BOEHRINGER INGELHEIM INTERNATIONAL GMBH reassignment BOEHRINGER INGELHEIM INTERNATIONAL GMBH ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: RIES, UWE, RALL, WERNER, SCHNAUBELT, JUERGEN, DURAN, ADIL, KRUEGER, THOMAS, LEUTER, ZENO A., SOYKA, RAINER
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
    • C07D265/36—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings condensed with one six-membered ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/08—Preparation of nitro compounds by substitution of hydrogen atoms by nitro groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C221/00—Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/12—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
    • C07C233/13—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • C07C233/17—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • C07C233/18—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
    • C07C45/71—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form being hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
    • C07C49/84—Ketones containing a keto group bound to a six-membered aromatic ring containing ether groups, groups, groups, or groups
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Definitions

  • the present invention relates to a process for preparing betamimetics of formula 1, wherein
  • Betamimetics ( ⁇ -adrenergic substances) are known from the prior art. For example reference may be made in this respect to the disclosure of U.S. Pat. No. 4,460,581, which proposes betamimetics for the treatment of a range of diseases.
  • the aim of the present invention is therefore to provide a method of producing betamimetics which on the one hand confer a therapeutic benefit in the treatment of COPD or asthma and are also characterised by a longer duration of activity and can thus be used to prepare pharmaceutical compositions with a longer duration of activity.
  • a particular aim of the invention is to prepare betamimetics which, by virtue of their long-lasting effect, can be used to prepare a drug for administration once a day for treating COPD or asthma.
  • a further objective of the invention apart from those mentioned above, is to prepare betamimetics which are not only exceptionally potent but are also characterised by a high degree of selectivity with respect to the ⁇ 2 -adrenoceptor.
  • the present invention relates to a process for preparing a compound of formula 1, wherein
  • a compound of formula 1a is reacted with a compound of formula 1b in a suitable solvent.
  • suitable solvents which may be used are organic solvents, while particularly preferred solvents are selected from among tetrahydrofuran, toluene, ethanol, n-propanol, n-butanol, n-butylacetate, dimethylformamide, methoxyethanol, ethyleneglycol and dioxane.
  • particularly preferred solvents are n-propanol, tetrahydrofuran and dioxane, while dioxane and n-propanol are of particular importance.
  • compound 1b may optionally also be used in excess, for example in amounts of up to 3 equivalents, preferably up to 2.5 equivalents, particularly preferably about 1 to 2, optionally 1 to 1.5 equivalents based on the compound 1a used.
  • the reaction is preferably carried out at elevated temperature, preferably at a temperature above 40° C., particularly preferably at a temperature above 50° C. Particularly preferably, the reaction mixture is heated to the boiling temperature of the solvent used.
  • reaction is then carried out over a period of about 1 to 72 hours, preferably 10 to 60 hours, particularly preferably 20 to 50 hours.
  • an organic polar solvent preferably a C 1-8 -alcohol or C 3-8 -ester, particularly preferably in ethanol or ethyl acetate, and filtered.
  • the filtrate is acidified, preferably with an inorganic acid, particularly preferably with hydrochloric acid and after a period of about 10 minutes to 12 hours, preferably 20 minutes to 6 hours, particularly preferably 30 minutes to 3 hours, the product is filtered off.
  • the protective group PG is preferably cleaved from compounds of formula 1a by hydrogenation in a suitable solvent.
  • suitable solvents include organic solvents, preferably organic, polar solvents, particularly preferred solvents are selected from among tetrahydrofuran, various C 3-8 -esters and C 1-8 -alcohols.
  • the solvents used are tetrahydrofuran, ethanol and methanol, while ethanol and methanol are of particular significance.
  • the hydrogenation in the process according to the invention preferably uses catalysts in the presence of hydrogen.
  • Preferred catalysts are suitable transition metal catalysts, preferably heterogeneous transition metal catalysts, particularly preferably palladium-containing catalysts, particularly a palladium-charcoal mixture.
  • the hydrogenation is preferably carried out in the presence of an excess of hydrogen.
  • the latter is provided according to the invention by a hydrogen pressure of 1 bar to 10 bar, preferably between 2 and 7 bar, particularly preferably between 2.5 and 4.5 bar.
  • the hydrogenation is carried out at elevated temperature, preferably from 25 to 70° C., particularly preferably from 30 to 60° C., particularly from 35 to 50° C.
  • the catalyst is removed, preferably by filtration.
  • a suitable organic solvent preferably a C 1-8 -alcohol or a mixture of C 1-8 -alcohols, particularly preferably from a mixture of methanol and an alcohol selected from among i-propanol, n-propanol and ethanol.
  • the compound of formula 1a is prepared by reacting a compound of formula 2a, wherein PG has the meaning given in claim 1 and R 4 denotes halogen, preferably bromine or chlorine.
  • a compound of formula 2a is reacted in a suitable solvent with DIP chloride (diisopinocampheylchloroborane).
  • suitable solvents are preferably organic solvents.
  • Preferred solvents are selected from among diethyl ether, tert-butyl-methylether 2-methyltetrahydrofuran, tetrahydrofuran, toluene and dioxane.
  • the solvents used are tert-butyl-methylether, tetrahydrofuran and dioxane, of which dioxane and tetrahydrofuran are of particular importance.
  • the DIP chloride may be used in pure form or in the form of a solution, preferably in an inert organic solvent, particularly preferably an aliphatic solvent, particularly pentane, hexane, heptane or octane.
  • the DIP chloride is added at reduced temperature in the reaction medium, the temperature preferably being below 0° C., particularly preferably below ⁇ 10° C.; more particularly the addition is carried out at ⁇ 20 to ⁇ 40° C.
  • the DIP chloride is added over a period of 10 min to 6 hours, preferably 30 min to 4 hours, particularly preferably 1 to 3 hours. In particular, the addition takes place over a period of 70 to 110 min.
  • DIP chloride Based on the compound 2a used, according to the invention at least stoichiometric amounts of DIP chloride are preferably used.
  • the DIP chloride may optionally also be used in excess, for example in amounts of up to 3 equivalents, preferably 2.5 equivalents, particularly preferably 1.5 to 2.5 equivalents based on the compound 2a used.
  • reaction mixture is stirred over a period of 10 min to 4 hours, preferably 30 min to 3 hours, particularly preferably 40 to 80 min; in particular, the reaction mixture is stirred for another 50 to 70 min after the addition has ended. During this time the reaction mixture is adjusted to a temperature of ⁇ 20 to 20° C., particularly preferably from ⁇ 10 to 10° C., particularly from ⁇ 5 to 5° C.
  • NaOH sodium hydroxide
  • the NaOH may also be used in excess, for example in amounts of up to 3 equivalents, preferably in amounts of up to 2.5 equivalents, particularly preferably 1.5 to 2.5 equivalents, based on the amount of DIP chloride used.
  • a pH value of 12 to 14, particularly preferably 12.5 to 13.5, particularly 12.7 to 13.3 is measured in the reaction mixture after the addition of NaOH has ended.
  • the reaction mixture is stirred over a period of 10 min to 4 hours, preferably 30 min to 3 hours, particularly preferably 40-80 min, and in particular the reaction mixture is stirred for a further 50-70 min.
  • the reaction mixture is adjusted to a temperature of 0 to 40° C., particularly preferably from 10 to 30° C., particularly from 15 to 25° C.
  • the reaction mixture is adjusted to a pH of 7 to 10, particularly preferably 8 to 9, particularly 8.2 to 8.8, with an acid, preferably an inorganic acid, particularly preferably hydrochloric acid.
  • the product can be isolated from the reaction mixture by extraction with an organic solvent and obtained as a solid by precipitation with another suitable organic solvent.
  • the compound of formula 2a is prepared by reacting a compound of formula 3a, wherein PG has the meaning given in claim 1 .
  • a compound of formula 3a is reacted with a halogenating reagent in a suitable solvent.
  • suitable solvents are organic solvents.
  • Preferred solvents are selected from among acetic acid, butyl acetate, methylene chloride, tetrahydrofuran, toluene and dioxane.
  • Particularly preferred solvents according to the invention are tetrahydrofuran and dioxane.
  • the halogenating reagent used is a brominating reagent, particularly preferably bromine, N-bromosuccinimide, benzyltrimethylammonium tribromide and tetrabutylammonium tribromide.
  • a brominating reagent particularly preferably bromine, N-bromosuccinimide, benzyltrimethylammonium tribromide and tetrabutylammonium tribromide.
  • the halogenating reagent may also be used in excess, for example in amounts of up to 3 equivalents, preferably in amounts of up to 2 equivalents, particularly preferably 1 to 1.5 equivalents, based on the compound 3a used.
  • the halogenating reagent may be added to the reaction mixture in a solvent, preferably in an organic, polar solvent, particularly preferably in methanol, ethanol and dioxane, particularly in methanol and dioxane, or in a mixture thereof, particularly in a mixture of methanol and dioxane.
  • a solvent preferably in an organic, polar solvent, particularly preferably in methanol, ethanol and dioxane, particularly in methanol and dioxane, or in a mixture thereof, particularly in a mixture of methanol and dioxane.
  • the reaction is preferably carried out at a temperature of 0 to 40° C., preferably at a temperature of 10 to 30° C., particularly preferably at a temperature of 15 to 25° C.
  • reaction mixture is stirred for a period of 10 min to 6 hours, preferably 30 min to 4 hours, particularly preferably 90 to 150 min.
  • the product water is added to the reaction mixture, wherein the mixture is cooled to a temperature of ⁇ 10° C. to 10° C., preferably 0 to 10° C., particularly preferably 0 to 5° C. and stirred for a period of 10 min to 4 hours, preferably 30 min to 2 hours, particularly preferably 50 to 70 min, after the addition of the water.
  • the product may be obtained after filtration or centrifugation and drying.
  • the compound of formula 3a is prepared by reacting a compound of formula 4a, wherein PG has the meaning given in claim 1 .
  • a compound of formula 4a is hydrogenated in a suitable solvent.
  • suitable solvents are organic solvents, preferably organic, polar solvents.
  • Particularly preferred solvents are selected from among dimethylformamide, N-methylpyrrolidinone, tetrahydrofuran, 2-methyltetrahydrofuran, toluene and dioxane.
  • the following are particularly preferred as solvents: dimethylformamide, tetrahydrofuran, 2-methyltetrahydrofuran and dioxane, wherein dimethylformamide and 2-methyltetrahydrofuran are of particular importance.
  • the hydrogenation in the process according to the invention preferably uses catalysts in the presence of hydrogen.
  • Preferred catalysts are suitable transition metal catalysts, preferably heterogeneous transition metal catalysts, particularly preferably nickel- or platinum-containing catalysts, particularly platinum oxide.
  • the hydrogenation is preferably carried out in the presence of an excess of hydrogen.
  • the latter is provided according to the invention by a hydrogen pressure of 1 bar to 10 bar, preferably from 2 to 7 bar, particularly preferably from 2.5 to 4.5 bar.
  • the hydrogenation is carried out at a temperature from 0 to 50° C., particularly preferably from 10 to 40° C., particularly from 20 to 30° C.
  • the catalyst is removed from the liquid phase, preferably by filtration.
  • the intermediate product 4a # in the solution, wherein PG has the meaning given in claim 1 may be isolated or further reacted directly to form a compound of formula 3a.
  • a base preferably a weak base, particularly preferably a carbonate, particularly potassium carbonate, is taken and the compound of formula 4a # is added in pure form or in a solution, particularly in the form of the solution filtered off from the hydrogenation catalyst in the preceding step.
  • a weak base particularly preferably a carbonate, particularly potassium carbonate
  • the base may optionally also be used in excess, for example in amounts of up to 6 equivalents, preferably in amounts of up to 4 equivalents, particularly preferably about 3 to 3.5 equivalents, based on the compound 4a used.
  • chloroacetyl chloride is added to the reaction mixture.
  • the chloroacetyl chloride is added over a period of 10 min to 2 hours, preferably 15 min to 1 hour, particularly preferably 25 to 35 min.
  • the chloroacetyl chloride may also be used in excess, for example in amounts of up to 4 equivalents, preferably in amounts of up to 3 equivalents, particularly preferably about 1.5 to 2 equivalents, based on the compound 4a used.
  • reaction mixture is stirred for a period of 10 min to 6 hours, preferably 1 to 4 hours, particularly preferably 140 to 160 min.
  • the reaction is preferably carried out at elevated temperature, preferably at a temperature of above 40° C., particularly preferably at a temperature of above 50° C., particularly preferably from 60° C. to 70° C.
  • the reaction is ended by the addition of water.
  • the compound of formula 3a can be purified and isolated by extraction of the reaction mixture with water and subsequent recrystallisation from a suitable organic solvent.
  • an aliphatic hydrocarbon particularly preferably an aliphatic cyclic hydrocarbon, particularly cyclohexane and methylcyclohexane.
  • the compound of formula 4a is prepared by reacting a compound of formula 5a, wherein PG has the meaning given in claim 1 .
  • a compound of formula 5a is reacted with a nitrogenating reagent in a suitable solvent.
  • suitable solvents include organic solvents and acids, preferably organic protic solvents and acids. Particularly preferred solvents are acetic acid and sulphuric acid, particularly acetic acid.
  • nitric acid for the nitrogenation in the process according to the invention it is preferable to use 6-65% nitric acid, as well as nitronium tetrafluoroborate or acetyl nitrate.
  • Nitric acid particularly 65% nitric acid, is particularly preferred.
  • the nitrogenating reagent preferably at least stoichiometric amounts are used according to the invention. If required the nitrogenating reagent may also be used in excess, for example in amounts of up to 2 equivalents, preferably in amounts of up to 1.5 equivalents, particularly preferably about 1 to 1.1 equivalents, based on the compound 5a used.
  • reaction mixture is stirred over a period of 10 min to 4 hours, preferably 20 min to 3 hours, particularly preferably 40 to 80 minutes.
  • reaction mixture is diluted with sufficient water to precipitate the compound of formula 4a from the solution.
  • crystallisation stirring is continued for a further 20 min to 3 hours, preferably 30 min to 2 hours, particularly preferably 40-80 min, at a temperature of 0° C. to 20° C., preferably at 5° C. to 15° C., particularly preferably at 8° C. to 12° C.
  • the compound of formula 4a may be obtained by separation from the liquid phase, preferably by filtration or centrifugation.
  • the compound of formula 5a is prepared by reacting a compound of formula 6a,
  • a compound of formula 6a is reacted in a suitable solvent with a protective group PG-A, wherein A denotes a suitable leaving group such as for example chlorine, bromine, iodine, methanesulphonyl, trifluoromethanesulphonyl or p-toluenesulphonyl.
  • A denotes a suitable leaving group such as for example chlorine, bromine, iodine, methanesulphonyl, trifluoromethanesulphonyl or p-toluenesulphonyl.
  • a protective group is used which can be eliminated as described with reference to the cleaving of the protective group PG from compounds of formula 1a.
  • an optionally substituted benzyl protective group is used.
  • the compound of formula 1b is prepared by reacting a compound of formula 2b, wherein R 1 , R 2 , R 3 and n have the meanings given in claims 1 to 5 and
  • a compound of formula 2b is reacted with a strong base in a suitable solvent.
  • suitable solvents include organic solvents; particularly preferred solvents are selected from among ethanol, 2-ethoxyethanol and ethyleneglycol or mixtures thereof. Particularly preferably, 2-ethoxyethanol or ethyleneglycol or a mixture thereof is used as the solvent according to the invention.
  • the mixture consists of equal parts by volume of 2-ethoxyethanol and ethyleneglycol, although a slight excess of one or other solvent is also possible.
  • the strong base used is particularly an inorganic hydroxide, preferably an alkaline earth or alkali metal hydroxide, particularly sodium hydroxide or potassium hydroxide. According to the invention potassium hydroxide is of particular importance.
  • the strong base may also be used in excess, for example in amounts of up to 8 equivalents, preferably in amounts of up to 6 equivalents, preferably about 2 to 4, particularly preferably 3.5 to 4.5 equivalents, based on the compound 2b used.
  • the reaction is preferably carried out at elevated temperature, preferably at a temperature of above 100° C., particularly preferably at a temperature of above 120° C. Particularly preferably the reaction mixture is heated to 140-160° C., particularly to 145-155° C.
  • the reaction mixture is diluted with a solvent and water.
  • Solvents of particular interest are toluene, xylene, heptane, methylcyclohexane or tert-butyl-methylether, preferably toluene or xylene.
  • the aqueous phase is eliminated, the organic phase is extracted with water in additional purification steps.
  • the water may be acidic, neutral or alkaline, by the use of common additives.
  • the organic phase is extracted once with acidified water and then with basic water.
  • the product may be obtained from the organic phase by elimination of the solvent.
  • the compound of formula 2b is prepared by reacting a compound of formula 3b, wherein R 1 , R 2 , R 3 and n have the meanings given in claims 1 to 5 .
  • a compound of formula 3b is reacted in a suitable solvent with acetonitrile in the presence of an acid.
  • suitable solvents are acids, preferably organic acids, while the particularly preferred solvent is acetic acid.
  • acetonitrile is used according to the invention.
  • the acetonitrile is used in excess, for example in amounts of up to 6 equivalents, preferably in amounts of up to 5 equivalents, particularly preferably about 2 to 4 equivalents, particularly 2.5 to 3.5 equivalents, based on the compound 3b used.
  • the acid in whose presence the reaction is carried out is preferably sulphuric acid, formic acid, p-toluenesulphonic acid, methanesulphonic acid, perchloric acid or polyphosphoric acid, particularly preferably sulphuric acid.
  • the acid may also be used in excess, for example in amounts of up to 2 equivalents, preferably in amounts of up to 1.5 equivalents, particularly preferably about 1 to 1.1 equivalents, based on the compound 5a used.
  • the reaction mixture is stirred for a period of 1 to 5 hours, preferably 2 to 4 hours, particularly preferably 170 to 190 min.
  • the reaction is preferably carried out at elevated temperature, preferably at a temperature of above 30° C., particularly preferably at a temperature of above 40° C., particularly preferably from 45° C. to 60° C.
  • elevated temperature preferably at a temperature of above 30° C., particularly preferably at a temperature of above 40° C., particularly preferably from 45° C. to 60° C.
  • reaction mixture is transferred into a second reactor which contains a cooled mixture of solvents.
  • suitable solvents include mixtures of polar and non-polar solvents, preferably aqueous, organic, polar and non-polar solvents.
  • Particularly preferred solvents as components of the mixture are selected from among water, tert-butyl-methylether, tetrahydrofuran, toluene, dioxane, hexane, cyclohexane and methylcyclohexane.
  • ingredients of the mixture water, tert-butylmethylether, tetrahydrofuran, toluene, cyclohexane and methylcyclohexane, while a mixture of water, tert-butylmethylether and methylcyclohexane is of particular importance.
  • the mixture of solvents is kept at a reduced temperature, preferably at a temperature of below 20° C., particularly preferably at a temperature below 15° C., particularly preferably 0° C. to 15° C.
  • the pH of the reaction mixture is raised, preferably into the basic range, particularly preferably from pH 8 to 12, particularly from pH 9 to 10.
  • an ammonia solution is used to raise the pH value.
  • reaction mixture is stirred for a period of 10 min to 3 hours, preferably 20 min to 2 hours, particularly preferably 50 to 70 min.
  • a product of greater purity can be obtained by further recrystallisation, or precipitation, e.g. with C 1-8 -alcohols and water.
  • the compound of formula 3b is prepared by reacting a compound of formula 4b, wherein R 1 , R 2 , R 3 and n have the meanings given in claims 1 to 5 .
  • a compound of formula 4b is subjected to a Grignard reaction in a suitable solvent with methylmagnesium bromide.
  • Organic solvents are suitable for use as the solvent.
  • Preferred solvents are selected from among diethyl ether, tert-butyl-methylether, tetrahydrofuran, toluene and dioxane. According to the invention it is particularly preferable to use tert-butyl-methylether, tetrahydrofuran and toluene as solvent.
  • the reaction is preferably carried out at ambient temperature, preferably at a temperature of 10 to 20° C., particularly preferably at a temperature of 15 to 25° C.
  • reaction mixture is stirred for a period of 10 min to 3 hours, preferably 20 min to 2 hours, particularly preferably 50 to 70 min.
  • reaction mixture water and an acid, preferably sulphuric acid, are added to the reaction mixture.
  • an acid preferably sulphuric acid
  • the product may be isolated by elimination of the solvent.
  • the purity of the product can be increased by recrystallisation from an organic non-polar solvent, preferably n-heptane.
  • the invention further relates to the new intermediate products of formula 3a, wherein PG has the meaning given in claim 1 .
  • the invention further relates to the new intermediate products of formula 4a, wherein PG has the meaning given in claim 1 .
  • the invention further relates to the new intermediate products of formula 4a # , wherein PG has the meaning given in claim 1 .
  • the invention further relates to the new intermediate products of formula 2b, wherein R 1 , R 2 , R 3 and n have the meanings given in claims 1 to 5 and
  • the subject matter of the invention also includes a process for preparing compounds of formula 2a, wherein PG has the meaning given in claim 1 and R 4 denotes halogen, preferably bromine or chlorine, characterised in that a compound of formula 3a, wherein PG has the meaning given in claim 1 , is reacted with the halogenating reagent selected from among tetrabutylammonium tribromide, benzyltrimethylammonium dichloriodide, N-bromo-succinimide, N-chloro-succinimide, sulphuryl chloride and bromine/dioxane, preferably tetrabutylammonium tribromide or N-bromo-succinimide.
  • the halogenating reagent selected from among tetrabutylammonium tribromide, benzyltrimethylammonium dichloriodide, N-bromo-succinimide, N-chloro-s
  • the subject matter of the invention also includes a process for preparing compounds of formula 3a, wherein PG has the meaning given in claim 1 , characterised in that a compound of formula 4a, wherein PG has the meaning given in claim 1 , is subjected to catalytic hydrogenation and then reacted with chloroacetyl chloride.
  • the subject matter of the invention also includes a process according to claim 16 , wherein a compound of formula 4a # , wherein PG has the meaning given in claim 1 , is formed as the intermediate product of the hydrogenation.
  • the subject matter of the invention also includes a process for preparing compounds of formula 4a, wherein PG has the meaning given in claim 1 and is characterised in that a compound of formula 5a, wherein PG has the meaning given in claim 1 , is reacted with a nitrogenating reagent selected from among 65% nitric acid, potassium nitrate/sulphuric acid or nitronium tetrafluoroborate, preferably 65% nitric acid.
  • a nitrogenating reagent selected from among 65% nitric acid, potassium nitrate/sulphuric acid or nitronium tetrafluoroborate, preferably 65% nitric acid.
  • the subject matter of the invention also includes a process for preparing compounds of formula 1b, wherein R 1 , R 2 , R 3 and n have the meanings given in claims 1 to 5 , characterised in that a compound of formula 2b, wherein R 1 , R 2 , R 3 and n have the meanings given in claims 1 to 5 and R 5 denotes Me, is reacted with a base selected from among potassium hydroxide, sodium hydroxide, lithium hydroxide and caesium hydroxide, preferably potassium hydroxide or sodium hydroxide.
  • the subject matter of the invention also includes a process for preparing compounds of formula 2b, wherein R 1 , R 2 , R 3 and n have the meanings given in claims 1 to 5 and
  • an “organic solvent” is meant, within the scope of the invention, an organic, low-molecular substance which can dissolve other organic substances by a physical method.
  • the prerequisite for the solvent is that neither the dissolving substance nor the dissolved substance should be chemically altered during the dissolving process, i.e. the components of the solution should be recoverable in their original form by physical separation processes such as distillation, crystallisation, sublimation, evaporation or adsorption.
  • the pure solvents but also mixtures that combine the dissolving properties may be used. Examples include:
  • C 1-4 -alkyl (including those which are part of other groups) are meant branched and unbranched alkyl groups with 1 to 4 carbon atoms. Examples include: methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl or tert-butyl. In some cases the abbreviations Me, Et, n-Pr, i-Pr, n-Bu, i-Bu, t-Bu, etc. are also used for the above-mentioned groups. Unless stated otherwise, the definitions propyl and butyl include all the possible isomeric forms of the groups in question. Thus, for example, propyl includes n-propyl and iso-propyl, butyl includes iso-butyl, sec-butyl and tert-butyl etc.
  • C 1-4 -alkylene (including those which are part of other groups) are meant branched and unbranched alkylene groups with 1 to 4 carbon atoms. Examples include: methylene, ethylene, propylene, 1-methylethylene, butylene, 1-methylpropylene, 1,1-dimethylethylene or 1,2-dimethylethylene. Unless stated otherwise, the definitions propylene and butylene include all the possible isomeric forms of the groups in question with the same number of carbons. Thus, for example, propyl also includes 1-methylethylene and butylene includes 1-methylpropylene, 1,1-dimethylethylene, 1,2-dimethylethylene.
  • C 1-8 -alcohol branched and unbranched alcohols with 1 to 8 carbon atoms and one or two hydroxy groups. Alcohols with 1 to 4 carbon atoms are preferred. Examples include: methanol, ethanol, n-propanol, iso-propanol, n-butanol, iso-butanol, sec-butanol or tert-butanol. In some cases the abbreviations MeOH, EtOH, n-PrOH, i-PrOH, n-BuOH, i-BuOH, t-BuOH, etc. are optionally also used for the above-mentioned molecules.
  • propanol, butanol, pentanol and hexanol include all the possible isomeric forms of the groups in question.
  • propanol includes n-propanol and iso-propanol
  • butanol includes iso-butanol, sec-butanol and tert-butanol etc.
  • C 3-8 -esters are meant branched and unbranched esters with a total of 3 to 8 carbon atoms. Esters of acetic acid with 3 to 6 carbon atoms are preferred. Examples include: methyl acetate, ethyl acetate, n-propyl acetate, i-propyl acetate or n-butyl acetate, of which ethyl acetate is preferred.
  • Halogen within the scope of the present invention denotes fluorine, chlorine, bromine or iodine. Unless stated to the contrary, fluorine, chlorine and bromine are regarded as preferred halogens.
  • Protective groups for the purposes of the present invention is a collective term for organic groups with which certain functional groups of a molecule containing a number of active centres can temporarily be protected from attack by reagents so that reactions take place only at the desired (unprotected) sites.
  • the protective groups should be introduced selectively under mild conditions. They must be stable for the duration of the protection under all the conditions of the reactions and purifying procedures which are to be carried out; racemisations and epimerisations must be suppressed. Protective groups should be capable of being cleaved again under mild conditions selectively and ideally in high yields.
  • protective groups are optionally substituted benzyl, diphenylmethyl, trityl, tosyl, mesyl or triflate, of which optionally substituted benzyl is particularly preferred.
  • the moist product is dissolved in 50 litres of methanol.
  • the resulting solution is filtered clear and the pressure filter is rinsed with 10 litres of methanol.
  • 52 l methanol are distilled off under a weak vacuum (about 500 mbar). If there is no crystal formation, the distillation residue is inoculated.
  • the methylisobutylketone is largely distilled off in vacuo, and the residue is dissolved in 80 l methanol at 60° C. The solution is cooled to 0° C. and stirred for 1 hour at this temperature to complete the crystallisation.
  • the suspension is cooled to 5° C. and stirred for 1 hour at this temperature.
  • the product is separated by centrifuging and washed with 30 l water as well as with a mixture of 7.5 l tert-butylmethylether and 7.5 l methylcyclohexane.
  • the damp product is heated to 75° C. in 25 l ethanol (96%) and at this temperature combined with 30 l water.
  • the solution is stirred for 15 minutes at 85° C., then cooled to 2° C. and stirred for 1 hour at this temperature.
  • the product is isolated, washed with a mixture of 5 l water and 5 l ethanol (96%) and dried.
  • R 1 , R 2 and R 3 may have the following meanings, for example: R 1 R 2 R 3 Example 1 H H OMe Example 2 2-F H F Example 3 3-F 5-F H Example 4 H H OEt Example 5 H H F
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050222144A1 (en) * 2002-11-15 2005-10-06 Boehringer Ingelheim Pharma Gmbh & Co. Kg Medicaments for the treatment of chronic obstructive pulmonary disease
US20050256115A1 (en) * 2004-05-14 2005-11-17 Boehringer Ingelheim International Gmbh Aerosol formulation for the inhalation of beta-agonists
US20050255050A1 (en) * 2004-05-14 2005-11-17 Boehringer Ingelheim International Gmbh Powder formulations for inhalation, comprising enantiomerically pure beta agonists
US20050272726A1 (en) * 2004-04-22 2005-12-08 Boehringer Ingelheim International Gmbh Novel medicaments for the treatment of respiratory diseases
US20070027148A1 (en) * 2004-05-14 2007-02-01 Philipp Lustenberger New enantiomerically pure beta agonists, process for the manufacture thereof, and use thereof as medicaments
US20110124859A1 (en) * 2005-08-15 2011-05-26 Boehringer Ingelheim International Gmbh Process for the manufacturing of betamimetics
US10059678B2 (en) 2014-09-09 2018-08-28 G. Pratap REDDY Process for preparing olodaterol and intermediates thereof

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100022770A1 (en) * 2007-01-25 2010-01-28 Boehringer Ingelheim International Gmbh Process for the manufacturing of beta mimetics
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WO2018108669A1 (en) 2016-12-12 2018-06-21 Boehringer Ingelheim International Gmbh Nintedanib for use in methods for the treatment of interstitial lung diseases by coadministration with olodaterol
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CN112592323B (zh) * 2020-06-11 2022-07-01 上海谷森医药有限公司 奥达特罗及其盐的制备方法

Citations (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4215119A (en) * 1976-03-09 1980-07-29 Boehringer Ingelheim Gmbh Aminoalkyl-substituted benzimidazolidin-2-ones
US4460581A (en) * 1982-10-12 1984-07-17 Boehringer Ingelheim Kg (1-Hydroxy-2-amino-alkyl)-substituted benzoxazinones and benzoxazolinones
US4570630A (en) * 1983-08-03 1986-02-18 Miles Laboratories, Inc. Medicament inhalation device
US4656168A (en) * 1980-12-23 1987-04-07 Merck & Co., Inc. (3-aralkylamino-2-or-propoxy)heterocyclic compounds in method of effecting bronchodilation
US5035237A (en) * 1985-07-30 1991-07-30 Newell Robert E Devices for administering medicaments to patients
US5223614A (en) * 1987-12-19 1993-06-29 Boehringer Ingelheim Gmbh New quaternary ammonium compounds, their preparation and use
US5472143A (en) * 1992-09-29 1995-12-05 Boehringer Ingelheim International Gmbh Atomising nozzle and filter and spray generation device
US5497944A (en) * 1990-03-21 1996-03-12 Dmw (Technology) Limited Atomising devices and methods
US5750701A (en) * 1994-03-15 1998-05-12 Smithkline Beecham Plc Heterocyclic ethanolamine derivatives with β-adrenoreceptor agonistic activity
US5947118A (en) * 1993-06-03 1999-09-07 Boehringer Ingelheim Kg Capsule holder
US5964416A (en) * 1995-10-04 1999-10-12 Boehringer Ingelheim Gmbh Device for producing high pressure in a fluid in miniature
US6007676A (en) * 1992-09-29 1999-12-28 Boehringer Ingelheim International Gmbh Atomizing nozzle and filter and spray generating device
US6176442B1 (en) * 1995-10-04 2001-01-23 Boehringer Ingelheim International Gmbh Device for mounting a component exposed to a pressurized fluid
US20010008632A1 (en) * 1996-12-20 2001-07-19 Bernhard Freund Aqueous medicament preparations for the production of propellent gas-free aerosols
US20020022625A1 (en) * 2000-04-27 2002-02-21 Alexander Walland Betamimetics having a long-lasting activity, processes for preparing them, and their use as medicaments
US6453795B1 (en) * 1995-12-05 2002-09-24 Boehringer Ingelheim International Gmbh Locking mechanism for a spring-actuated device
US20030018019A1 (en) * 2001-06-23 2003-01-23 Boehringer Ingelheim Pharma Kg Pharmaceutical compositions based on anticholinergics, corticosteroids and betamimetics
US6582678B2 (en) * 1993-10-26 2003-06-24 Vectura Limited Carrier particles for use in dry powder inhalers
US20030152523A1 (en) * 2000-02-08 2003-08-14 Martin Gary Peter Pharmaceutical composition for pulmonary delivery
US20040002502A1 (en) * 2002-04-12 2004-01-01 Boehringer Ingelheim Pharma Gmbh & Co. Kg Medicament combinations comprising heterocyclic compounds and a novel anticholinergic
US20040010003A1 (en) * 2002-04-12 2004-01-15 Boehringer Ingelheim Pharma Gmbh & Co. Kg Medicaments comprising betamimetics and a novel anticholinergic
US20040024007A1 (en) * 2001-03-07 2004-02-05 Boehringer Ingelheim Pharma Kg Pharmaceutical compositions based on anticholinergics and PDE-IV inhibitors
US20040044020A1 (en) * 2002-07-09 2004-03-04 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pharmaceutical compositions based on novel anticholinergics and p38 kinase inhibitors
US20040048887A1 (en) * 2002-07-09 2004-03-11 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pharmaceutical compositions based on anticholinergics and EGFR kinase inhibitors
US20040048886A1 (en) * 2002-07-09 2004-03-11 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pharmaceutical compositions based on new anticholinergics and NK1 receptor antagonists
US6706726B2 (en) * 2000-10-14 2004-03-16 Boehringer Ingelheim Pharma Gmbh & Co. Kg Anticholinergics which may be used as medicaments as well as processes for preparing them
US20040058950A1 (en) * 2002-07-09 2004-03-25 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pharmaceutical compositions based on anticholinergics and PDE-IV inhibitors
US6747154B2 (en) * 2002-01-12 2004-06-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg Process for preparing scopine esters
US20040166065A1 (en) * 2002-08-14 2004-08-26 Boehringer Ingelheim Pharma Gmbh & Co. Kg Aerosol formulation for inhalation comprising an anticholinergic
US20040228805A1 (en) * 2002-08-17 2004-11-18 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pharmaceutical compositions for inhalation containing an anticholinergic, corticosteroid and betamimetic
US20050004228A1 (en) * 2003-05-27 2005-01-06 Boehringer Ingelheim International Gmbh Long-acting drug combinations for the treatment of respiratory complaints
US20050008578A1 (en) * 2003-07-11 2005-01-13 Boehringer Ingelheim International Gmbh HFC solution formulations containing an anticholinergic
US6846413B1 (en) * 1997-09-26 2005-01-25 Boehringer Ingelheim International Gmbh Microstructured filter
US20050025718A1 (en) * 2003-07-31 2005-02-03 Boehringer Ingelheim International Gmbh Medicaments for inhalation comprising an anticholinergic and a betamimetic
US20050063817A1 (en) * 2003-09-23 2005-03-24 Hee-Keun Park Heat dissipation fan
US20050101625A1 (en) * 2003-09-26 2005-05-12 Boehringer Ingelheim International Gmbh Aerosol formulation for inhalation comprising an anticholinergic
US20050186175A1 (en) * 2004-02-20 2005-08-25 Boehringer Ingelheim International Gmbh Pharmaceutical compositions based on benzilic acid esters and soluble TNF receptor fusion proteins
US6951888B2 (en) * 2002-10-04 2005-10-04 Boehringer Ingelheim Pharma Gmbh & Co. Kg Betamimetics with a prolonged duration of activity, processes for preparing them, and their use as pharmaceutical compositions
US20050222144A1 (en) * 2002-11-15 2005-10-06 Boehringer Ingelheim Pharma Gmbh & Co. Kg Medicaments for the treatment of chronic obstructive pulmonary disease
US20050239778A1 (en) * 2004-04-22 2005-10-27 Boehringer Ingelheim International Gmbh Novel medicament combinations for the treatment of respiratory diseases
US20050256115A1 (en) * 2004-05-14 2005-11-17 Boehringer Ingelheim International Gmbh Aerosol formulation for the inhalation of beta-agonists
US20050255050A1 (en) * 2004-05-14 2005-11-17 Boehringer Ingelheim International Gmbh Powder formulations for inhalation, comprising enantiomerically pure beta agonists
US20050256114A1 (en) * 2004-05-14 2005-11-17 Boehringer Ingelheim International Gmbh Novel long acting bronchodilators for the treatment of respiratory diseases
US7084153B2 (en) * 2002-04-12 2006-08-01 Boehringer Ingelheim Pharma Gmbh & Co. Kg Medicaments comprising steroids and a novel anticholinergic
US20060189607A1 (en) * 2005-02-19 2006-08-24 Boehringer Ingelheim International Gmbh Long-acting betamimetics for the treatment of respiratory complaints
US7160882B2 (en) * 2004-01-23 2007-01-09 Boehringer Ingelheim International Gmbh Long acting β-2-agonists and their use as medicaments
US20070027148A1 (en) * 2004-05-14 2007-02-01 Philipp Lustenberger New enantiomerically pure beta agonists, process for the manufacture thereof, and use thereof as medicaments
US20070088030A1 (en) * 2005-10-10 2007-04-19 Barbara Niklaus-Humke Aerosol formulations for the inhalation of beta-agonists
US20070086957A1 (en) * 2005-10-10 2007-04-19 Thierry Bouyssou Combination of medicaments for the treatment of respiratory diseases
US7307076B2 (en) * 2004-05-13 2007-12-11 Boehringer Ingelheim International Gmbh Beta agonists for the treatment of respiratory diseases
US20080041369A1 (en) * 2006-08-18 2008-02-21 Kirsten Radau Aerosol formulation for the inhalation of beta agonists
US20080041370A1 (en) * 2006-08-18 2008-02-21 Kirsten Radau Aerosol formulation for the inhalation of beta agonists
US20080280897A1 (en) * 2005-11-09 2008-11-13 Michael Aven Aerosol Formulation for Inhalation

Family Cites Families (62)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1144713B (de) * 1960-10-14 1963-03-07 Troponwerke Dinklage & Co Verfahren zur Herstellung von N-substituierten Carbonsaeureamiden
US4252951A (en) * 1979-10-09 1981-02-24 Eli Lilly And Company Isolation of syn-7-(2-amino-4-thiazolyl)-(methoxyimino)acetamido-3-acetoxymethyl-3-cephem-4-carboxylic acid
FR2510104A1 (fr) 1981-07-27 1983-01-28 Rhone Poulenc Agrochimie Composes herbicides derives d'acides phenoxybenzoiques
JPS5824431A (ja) 1981-08-06 1983-02-14 Sumitomo Rubber Ind Ltd エラストマ−物品の予熱方法
DE3134590A1 (de) 1981-09-01 1983-03-10 Boehringer Ingelheim KG, 6507 Ingelheim Neue benzo-heterocyclen
DE3327400A1 (de) * 1983-07-29 1985-02-07 Alfred Teves Gmbh, 6000 Frankfurt Vorrichtung zur erfassung der umfangsgeschwindigkeit einer in drehung versetzbaren zahnscheibe
SE453566B (sv) 1986-03-07 1988-02-15 Draco Ab Anordning vid pulverinhalatorer
DE3743265A1 (de) 1987-12-19 1989-06-29 Boehringer Ingelheim Kg Neue ammoniumverbindungen, ihre herstellung und verwendung
US5502078A (en) * 1991-05-28 1996-03-26 Zeneca Limited Chemical compounds
WO1994013263A1 (en) * 1992-12-09 1994-06-23 Jager Paul D Stabilized medicinal aerosol solution formulations
JP3875993B2 (ja) * 1995-06-27 2007-01-31 ベーリンガー インゲルハイム コマンディトゲゼルシャフト 噴射剤を含まないエアゾールを製造するための新規で安定な医薬調製物
US5753417A (en) * 1996-06-10 1998-05-19 Sharp Microelectronics Technology, Inc. Multiple exposure masking system for forming multi-level resist profiles
DE59600683D1 (de) * 1996-11-27 1998-11-19 Pfleger R Chem Fab Verwendung von Trospiumchlorid zur Herstellung eines Arzneimittels zur Behandlung von Blasenkrankheiten
DE19724397A1 (de) * 1997-06-10 1999-01-14 Bayer Ag UV-Stabilisatoren für Siloxan-Systeme
GB0009592D0 (en) * 2000-04-18 2000-06-07 Glaxo Group Ltd Respiratory combinations
US6960597B2 (en) * 2000-06-30 2005-11-01 Orth-Mcneil Pharmaceutical, Inc. Aza-bridged-bicyclic amino acid derivatives as α4 integrin antagonists
TR200402579T4 (tr) 2000-10-12 2004-12-21 Boehringer Ingelheim Pharma Gmbh & Co. Kg Kristalin monohidrat, bunun imalat yöntemi ve bir ilaç maddesinin imalatında kullanımı
DE10050994A1 (de) 2000-10-14 2002-04-18 Boehringer Ingelheim Pharma Neue als Arneimittel einsetzbare Anticholinergika sowie Verfahren zu deren Herstellung
US6852728B2 (en) * 2000-10-14 2005-02-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg Anticholinergics, processes for preparing them, and pharmaceutical compositions containing them
US20020189610A1 (en) * 2001-02-01 2002-12-19 Karl-Heinz Bozung Pharmaceutical compositions containing an ipratropium salt and a betamimetic
GB0107106D0 (en) 2001-03-21 2001-05-09 Boehringer Ingelheim Pharma Powder inhaler formulations
SI1401445T1 (sl) 2001-06-22 2007-02-28 Boehringer Ingelheim Pharma Kristalinicen antiholinergik, postopek za njegovo pripravo in njegova uporaba za pripravo zdravila
DE10130371A1 (de) 2001-06-23 2003-01-02 Boehringer Ingelheim Pharma Neue Arzneimittelkompositionen auf der Basis von Anticholinergika, Corticosteroiden und Betamimetika
GB2377934B (en) 2001-07-25 2005-01-12 Portela & Ca Sa Method for the nitration of phenolic compounds
DE10141377A1 (de) 2001-08-23 2003-03-13 Boehringer Ingelheim Pharma Aufstreuverfahren zur Herstellung von Pulverformulierungen
US6696462B2 (en) * 2002-01-31 2004-02-24 Boehringer Ingelheim Pharma Gmbh & Co. Kg Anticholinergics, processes for the preparation thereof, and pharmaceutical compositions
DE10203753A1 (de) 2002-01-31 2003-08-14 Boehringer Ingelheim Pharma Neue Xanthencarbonsäureester, Verfahren zu deren Herstellung sowie deren Verwendung als Arzneimittel
DE10212264A1 (de) 2002-03-20 2003-10-02 Boehringer Ingelheim Pharma Kristallines Mikronisat, Verfahren zu dessen Herstellung und dessen Verwendung zur Herstellung eines Arzneimittels
UA80123C2 (en) 2002-04-09 2007-08-27 Boehringer Ingelheim Pharma Inhalation kit comprising inhalable powder of tiotropium
ES2203327B1 (es) 2002-06-21 2005-06-16 Almirall Prodesfarma, S.A. Nuevos carbamatos de quinuclidina y composiciones farmaceuticas que los contienen.
DE10230751A1 (de) 2002-07-09 2004-01-22 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Arzneimittelkompositionen auf der Basis neuer Anticholinergika und EGFR-Kinase-Hemmern
DE10237739A1 (de) 2002-08-17 2004-02-26 Boehringer Ingelheim Pharma Gmbh & Co. Kg Inhalative Arzneimittel enthaltend ein neues Anticholinergikum in Kombination mit Corticosteroiden und Betamimetika
DE10246374A1 (de) 2002-10-04 2004-04-15 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Betamimetika mit verlängerter Wirkungsdauer, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel
DE10253220A1 (de) 2002-11-15 2004-05-27 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Dihydroxy-Methyl-Phenyl-Derivate, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel
DE10253282A1 (de) 2002-11-15 2004-05-27 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Arzneimittel zur Behandlung von chronisch obstruktiver Lungenerkrankung
US7250426B2 (en) * 2002-11-29 2007-07-31 Boehringer Ingelheim Pharma Gmbh & Co Kg Tiotropium-containing pharmaceutical combination for inhalation
JP2006510661A (ja) * 2002-12-06 2006-03-30 ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー Ｐｉ３ｋの阻害剤としてのベンズオキサジン−３−オン類及びその誘導体
PT1613315E (pt) * 2003-04-04 2009-04-22 Novartis Ag Derivados da quinolina-2-ona para o tratamento de doenças das vias aéreas respiratórias
US20050026948A1 (en) * 2003-07-29 2005-02-03 Boehringer Ingelheim International Gmbh Medicaments for inhalation comprising an anticholinergic and a betamimetic
NZ545442A (en) 2003-07-29 2010-05-28 Boehringer Ingelheim Int Medicaments for inhalation comprising betamimetics and an aclidinium salt known as 3-(2-hydroxy-2,2-dithiophen-2-yl-acetoxy)-1-(3-phenoxypropyl)-l-azoniabicyclo[2.2.2]octane
US20050154006A1 (en) * 2004-01-09 2005-07-14 Boehringer Ingelheim International Gmbh Pharmaceutical compositions based on a scopineester and nicotinamide derivatives
DE102004019540A1 (de) 2004-04-22 2005-11-10 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Arzneimittelkombinationen zur Behandlung von Atemwegserkrankungen
EP1577306A1 (de) 2004-03-17 2005-09-21 Boehringer Ingelheim Pharma GmbH & Co.KG Neue Benzoxazinonderivate als langwirksame Betamimetika zur Behandlung von Atemwegserkrankungen
US7244728B2 (en) * 2004-03-17 2007-07-17 Boehringer Ingelheim International Gmbh Long acting betamimetics for the treatment of respiratory diseases
DE102004019539A1 (de) 2004-04-22 2005-11-10 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Arzneimittel zur Behandlung von Atemwegserkrankungen
SG152237A1 (en) 2004-04-22 2009-05-29 Boehringer Ingelheim Int Pharmaceutical combinations containing benzoxazine for treating respiratory diseases
US20050272726A1 (en) 2004-04-22 2005-12-08 Boehringer Ingelheim International Gmbh Novel medicaments for the treatment of respiratory diseases
DE102004024452A1 (de) 2004-05-14 2005-12-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg Aerosolformulierung für die Inhalation von Betaagonisten
DE102004024451A1 (de) 2004-05-14 2005-12-22 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pulverformulierungen für die Inhalation, die Enantiomerenreine Betaagonisten enthalten
DE102004024454A1 (de) 2004-05-14 2005-12-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Enantiomerenreine Betaagonisten, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel
KR100598105B1 (ko) * 2004-06-17 2006-07-07 삼성전자주식회사 반도체 패턴 형성 방법
EP1778626A1 (en) * 2004-08-16 2007-05-02 Theravance, Inc. Compounds having beta2 adrenergic receptor agonist and muscarinic receptor antagonist activity
DE102004045648A1 (de) * 2004-09-21 2006-03-23 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Betamimetika zur Behandlung von Atemwegserkrankungen
JP5270343B2 (ja) * 2005-08-15 2013-08-21 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング ベータミメティックスの製造方法
CA2625375A1 (en) 2005-10-11 2007-04-19 Bayer Consumer Care Ag Mixture of iron and copper salts masking mettalic taste
US7579137B2 (en) * 2005-12-24 2009-08-25 International Business Machines Corporation Method for fabricating dual damascene structures
TW200815054A (en) 2006-06-19 2008-04-01 Otsuka Pharma Co Ltd Methods of using a thiazole derivative
TWI482772B (zh) 2006-08-21 2015-05-01 Astrazeneca Ab 適合口服且包含三唑并[4,5-d]嘧啶衍生物之組合物
US20100022770A1 (en) 2007-01-25 2010-01-28 Boehringer Ingelheim International Gmbh Process for the manufacturing of beta mimetics
KR20100088148A (ko) 2007-11-05 2010-08-06 베링거 인겔하임 인터내셔날 게엠베하 베타미메티카의 결정성 수화물 및 이의 약제로서의 용도
WO2010057927A1 (en) 2008-11-21 2010-05-27 Boehringer Ingelheim International Gmbh Aerosol formulation for the inhalation of beta agonists
WO2010057928A1 (en) 2008-11-21 2010-05-27 Boehringer Ingelheim International Gmbh Aerosol formulation for the inhalation of beta agonists

Patent Citations (64)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4215119A (en) * 1976-03-09 1980-07-29 Boehringer Ingelheim Gmbh Aminoalkyl-substituted benzimidazolidin-2-ones
US4656168A (en) * 1980-12-23 1987-04-07 Merck & Co., Inc. (3-aralkylamino-2-or-propoxy)heterocyclic compounds in method of effecting bronchodilation
US4460581A (en) * 1982-10-12 1984-07-17 Boehringer Ingelheim Kg (1-Hydroxy-2-amino-alkyl)-substituted benzoxazinones and benzoxazolinones
US4570630A (en) * 1983-08-03 1986-02-18 Miles Laboratories, Inc. Medicament inhalation device
US5035237A (en) * 1985-07-30 1991-07-30 Newell Robert E Devices for administering medicaments to patients
US5223614A (en) * 1987-12-19 1993-06-29 Boehringer Ingelheim Gmbh New quaternary ammonium compounds, their preparation and use
US5497944A (en) * 1990-03-21 1996-03-12 Dmw (Technology) Limited Atomising devices and methods
US6007676A (en) * 1992-09-29 1999-12-28 Boehringer Ingelheim International Gmbh Atomizing nozzle and filter and spray generating device
US5472143A (en) * 1992-09-29 1995-12-05 Boehringer Ingelheim International Gmbh Atomising nozzle and filter and spray generation device
US5911851A (en) * 1992-09-29 1999-06-15 Boehringer Ingelheim International Gmbh Atomizing nozzle and filter and spray generating device
US6503362B1 (en) * 1992-09-29 2003-01-07 Boehringer Ingelheim International Gmbh Atomizing nozzle an filter and spray generating device
US5947118A (en) * 1993-06-03 1999-09-07 Boehringer Ingelheim Kg Capsule holder
US6582678B2 (en) * 1993-10-26 2003-06-24 Vectura Limited Carrier particles for use in dry powder inhalers
US5750701A (en) * 1994-03-15 1998-05-12 Smithkline Beecham Plc Heterocyclic ethanolamine derivatives with β-adrenoreceptor agonistic activity
US5964416A (en) * 1995-10-04 1999-10-12 Boehringer Ingelheim Gmbh Device for producing high pressure in a fluid in miniature
US6176442B1 (en) * 1995-10-04 2001-01-23 Boehringer Ingelheim International Gmbh Device for mounting a component exposed to a pressurized fluid
US6453795B1 (en) * 1995-12-05 2002-09-24 Boehringer Ingelheim International Gmbh Locking mechanism for a spring-actuated device
US20010008632A1 (en) * 1996-12-20 2001-07-19 Bernhard Freund Aqueous medicament preparations for the production of propellent gas-free aerosols
US6846413B1 (en) * 1997-09-26 2005-01-25 Boehringer Ingelheim International Gmbh Microstructured filter
US20030152523A1 (en) * 2000-02-08 2003-08-14 Martin Gary Peter Pharmaceutical composition for pulmonary delivery
US20020022625A1 (en) * 2000-04-27 2002-02-21 Alexander Walland Betamimetics having a long-lasting activity, processes for preparing them, and their use as medicaments
US20050137242A1 (en) * 2000-04-27 2005-06-23 Boehringer Ingelheim Pharma Gmbh & Co. Kg Betamimetics having a long-lasting activity, processes for preparing them, and their use as medicaments
US6706726B2 (en) * 2000-10-14 2004-03-16 Boehringer Ingelheim Pharma Gmbh & Co. Kg Anticholinergics which may be used as medicaments as well as processes for preparing them
US20040024007A1 (en) * 2001-03-07 2004-02-05 Boehringer Ingelheim Pharma Kg Pharmaceutical compositions based on anticholinergics and PDE-IV inhibitors
US20030018019A1 (en) * 2001-06-23 2003-01-23 Boehringer Ingelheim Pharma Kg Pharmaceutical compositions based on anticholinergics, corticosteroids and betamimetics
US6747154B2 (en) * 2002-01-12 2004-06-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg Process for preparing scopine esters
US7084153B2 (en) * 2002-04-12 2006-08-01 Boehringer Ingelheim Pharma Gmbh & Co. Kg Medicaments comprising steroids and a novel anticholinergic
US20040010003A1 (en) * 2002-04-12 2004-01-15 Boehringer Ingelheim Pharma Gmbh & Co. Kg Medicaments comprising betamimetics and a novel anticholinergic
US20040002502A1 (en) * 2002-04-12 2004-01-01 Boehringer Ingelheim Pharma Gmbh & Co. Kg Medicament combinations comprising heterocyclic compounds and a novel anticholinergic
US20040058950A1 (en) * 2002-07-09 2004-03-25 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pharmaceutical compositions based on anticholinergics and PDE-IV inhibitors
US20040048886A1 (en) * 2002-07-09 2004-03-11 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pharmaceutical compositions based on new anticholinergics and NK1 receptor antagonists
US20040048887A1 (en) * 2002-07-09 2004-03-11 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pharmaceutical compositions based on anticholinergics and EGFR kinase inhibitors
US20040044020A1 (en) * 2002-07-09 2004-03-04 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pharmaceutical compositions based on novel anticholinergics and p38 kinase inhibitors
US20040166065A1 (en) * 2002-08-14 2004-08-26 Boehringer Ingelheim Pharma Gmbh & Co. Kg Aerosol formulation for inhalation comprising an anticholinergic
US20040228805A1 (en) * 2002-08-17 2004-11-18 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pharmaceutical compositions for inhalation containing an anticholinergic, corticosteroid and betamimetic
US6951888B2 (en) * 2002-10-04 2005-10-04 Boehringer Ingelheim Pharma Gmbh & Co. Kg Betamimetics with a prolonged duration of activity, processes for preparing them, and their use as pharmaceutical compositions
US7056916B2 (en) * 2002-11-15 2006-06-06 Boehringer Ingelheim Pharma Gmbh & Co. Kg Medicaments for the treatment of chronic obstructive pulmonary disease
US20060106213A1 (en) * 2002-11-15 2006-05-18 Boehringer Ingelheim Pharma Gmbh & Co. Kg New Medicaments for the Treatment of Chronic Obstructive Pulmonary Disease
US20070155741A1 (en) * 2002-11-15 2007-07-05 Boehringer Ingelheim Pharma Gmbh & Co. Kg Medicaments for the Treatment of Chronic Obstructive Pulmonary Disease
US20080167298A1 (en) * 2002-11-15 2008-07-10 Boehringer Ingelheim Pharma Gmbh & Co. Kg Medicaments for the treatment of chronic obstructive pulmonary disease
US20050222144A1 (en) * 2002-11-15 2005-10-06 Boehringer Ingelheim Pharma Gmbh & Co. Kg Medicaments for the treatment of chronic obstructive pulmonary disease
US20050004228A1 (en) * 2003-05-27 2005-01-06 Boehringer Ingelheim International Gmbh Long-acting drug combinations for the treatment of respiratory complaints
US20050008578A1 (en) * 2003-07-11 2005-01-13 Boehringer Ingelheim International Gmbh HFC solution formulations containing an anticholinergic
US20050025718A1 (en) * 2003-07-31 2005-02-03 Boehringer Ingelheim International Gmbh Medicaments for inhalation comprising an anticholinergic and a betamimetic
US20050063817A1 (en) * 2003-09-23 2005-03-24 Hee-Keun Park Heat dissipation fan
US20050101625A1 (en) * 2003-09-26 2005-05-12 Boehringer Ingelheim International Gmbh Aerosol formulation for inhalation comprising an anticholinergic
US20070066609A1 (en) * 2004-01-23 2007-03-22 Thierry Bouyssou Long acting beta-2-agonists and their use as medicaments
US7160882B2 (en) * 2004-01-23 2007-01-09 Boehringer Ingelheim International Gmbh Long acting β-2-agonists and their use as medicaments
US20050186175A1 (en) * 2004-02-20 2005-08-25 Boehringer Ingelheim International Gmbh Pharmaceutical compositions based on benzilic acid esters and soluble TNF receptor fusion proteins
US20050239778A1 (en) * 2004-04-22 2005-10-27 Boehringer Ingelheim International Gmbh Novel medicament combinations for the treatment of respiratory diseases
US7307076B2 (en) * 2004-05-13 2007-12-11 Boehringer Ingelheim International Gmbh Beta agonists for the treatment of respiratory diseases
US7220742B2 (en) * 2004-05-14 2007-05-22 Boehringer Ingelheim International Gmbh Enantiomerically pure beta agonists, process for the manufacture thereof and use thereof as medicaments
US20070027148A1 (en) * 2004-05-14 2007-02-01 Philipp Lustenberger New enantiomerically pure beta agonists, process for the manufacture thereof, and use thereof as medicaments
US20050256114A1 (en) * 2004-05-14 2005-11-17 Boehringer Ingelheim International Gmbh Novel long acting bronchodilators for the treatment of respiratory diseases
US20050255050A1 (en) * 2004-05-14 2005-11-17 Boehringer Ingelheim International Gmbh Powder formulations for inhalation, comprising enantiomerically pure beta agonists
US20050256115A1 (en) * 2004-05-14 2005-11-17 Boehringer Ingelheim International Gmbh Aerosol formulation for the inhalation of beta-agonists
US20080293710A1 (en) * 2004-05-14 2008-11-27 Michael Aven Aerosol formulation for the inhalation of beta-agonists
US7491719B2 (en) * 2004-05-14 2009-02-17 Boehringer Ingelheim International Gmbh Enantiomerically pure beta agonists, process for the manufacture thereof, and use thereof as medicaments
US20060189607A1 (en) * 2005-02-19 2006-08-24 Boehringer Ingelheim International Gmbh Long-acting betamimetics for the treatment of respiratory complaints
US20070088030A1 (en) * 2005-10-10 2007-04-19 Barbara Niklaus-Humke Aerosol formulations for the inhalation of beta-agonists
US20070086957A1 (en) * 2005-10-10 2007-04-19 Thierry Bouyssou Combination of medicaments for the treatment of respiratory diseases
US20080280897A1 (en) * 2005-11-09 2008-11-13 Michael Aven Aerosol Formulation for Inhalation
US20080041369A1 (en) * 2006-08-18 2008-02-21 Kirsten Radau Aerosol formulation for the inhalation of beta agonists
US20080041370A1 (en) * 2006-08-18 2008-02-21 Kirsten Radau Aerosol formulation for the inhalation of beta agonists

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7786111B2 (en) 2002-11-15 2010-08-31 Boehringer Ingelheim Pharma Gmbh & Co. Kg Medicaments for the treatment of chronic obstructive pulmonary disease
US7727984B2 (en) 2002-11-15 2010-06-01 Boehringer Ingelheim Pharma Gmbh & Co., Kg Medicaments for the treatment of chronic obstructive pulmonary disease
US8044046B2 (en) 2002-11-15 2011-10-25 Boehringer Ingelheim Pharma Gmbh & Co Kg Medicaments for the treatment of chronic obstructive pulmonary disease
US20050222144A1 (en) * 2002-11-15 2005-10-06 Boehringer Ingelheim Pharma Gmbh & Co. Kg Medicaments for the treatment of chronic obstructive pulmonary disease
US20070155741A1 (en) * 2002-11-15 2007-07-05 Boehringer Ingelheim Pharma Gmbh & Co. Kg Medicaments for the Treatment of Chronic Obstructive Pulmonary Disease
US20080167298A1 (en) * 2002-11-15 2008-07-10 Boehringer Ingelheim Pharma Gmbh & Co. Kg Medicaments for the treatment of chronic obstructive pulmonary disease
US20050272726A1 (en) * 2004-04-22 2005-12-08 Boehringer Ingelheim International Gmbh Novel medicaments for the treatment of respiratory diseases
US20070027148A1 (en) * 2004-05-14 2007-02-01 Philipp Lustenberger New enantiomerically pure beta agonists, process for the manufacture thereof, and use thereof as medicaments
US20050256115A1 (en) * 2004-05-14 2005-11-17 Boehringer Ingelheim International Gmbh Aerosol formulation for the inhalation of beta-agonists
US7491719B2 (en) 2004-05-14 2009-02-17 Boehringer Ingelheim International Gmbh Enantiomerically pure beta agonists, process for the manufacture thereof, and use thereof as medicaments
US8034809B2 (en) 2004-05-14 2011-10-11 Boehringer Ingelheim International Gmbh Enantiomerically pure beta agonists, process for the manufacture thereof and use thereof as medicaments
US20050255050A1 (en) * 2004-05-14 2005-11-17 Boehringer Ingelheim International Gmbh Powder formulations for inhalation, comprising enantiomerically pure beta agonists
US20110124859A1 (en) * 2005-08-15 2011-05-26 Boehringer Ingelheim International Gmbh Process for the manufacturing of betamimetics
US8420809B2 (en) 2005-08-15 2013-04-16 Boehringer Ingelheim International Gmbh Process for the manufacturing of betamimetics
US10059678B2 (en) 2014-09-09 2018-08-28 G. Pratap REDDY Process for preparing olodaterol and intermediates thereof

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