- Synthesis of intermediate compound and [...] (by machine translation)
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Synthesis of intermediate compounds [a] and [...]. [Solution] a [...], asymmetric epoxidation, sulfonyl halide in the presence of base catalyst by sulfonation, alkylation of amines, such as synthesized by a series of cross-coupling reaction. [Effect] [...] important from the viewpoint of pharmacological value, high efficiency, low cost, and which meets the requirements of industrial, optical isomers may be prepared [...] and develop a method, which is very economical in social benefit. [Drawing] no (by machine translation)
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- Nebivolol synthetic method and intermediate compounds of the
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The present invention relates to a synthesis method and an intermediate compound of nebivolol. Specifically the invention relates to the method for synthesizing the nebivolol, the intermediate compound of the nebivolol, and a method for preparing the intermediate compound.
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- NEBIVOLOL SYNTHESIS METHOD AND INTERMEDIATE COMPOUND THEREOF
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The present invention relates to nebivolol synthesis method and intermediate compound thereof. Specifically, the present invention relates to a method for synthesizing nebivolol, intermediate compound thereof, and a method for preparing the intermediate compound.
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- PROCESS FOR THE SYNTHESIS OF INTERMEDIATES OF NEBIVOLOL
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The present invention relates to a novel process for the synthesis of the intermediate compounds constituted by chromanyl haloketones of formula III and 6-fluoro-2-(oxiran-2-yl) chromans of formula I. The intermediates thus obtained can be used for the sy
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Page/Page column 38-39
(2017/08/20)
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- A kind of nebivolol hydrochloride synthetic method
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The invention discloses a synthetic method of nebivolol. The synthetic method comprises the following steps: by taking a 2-amino-1-(-6-fluoro-2-chromanyl) ethanol diastereomer mixture as an initial raw material, firstly, recrystallizing and separating the 2-amino-1-(-6-fluoro-2-chromanyl) ethanol diastereomer mixture to respectively obtain corresponding diastereomers A and B; carrying out reactions such as diazotization, halogenation and cyclization on the diastereomer B to synthesize an epoxy compound; and then, carrying out a reaction on the obtained epoxy compound and the diastereomer A to obtain nebivolol. The method disclosed by the invention is mild in reaction condition, simple and convenient to operate and short in synthetic line, and is suitable for industrialized batch production of nebivolol.
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- PROCESS FOR PREPARATION OF NEBIVOLOL AND IT'S SALTS
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The present invention discloses a new process for preparation of Nebivolol or it's pharmaceutically acceptable salt. More particularly, the invention discloses an improved economical process for the preparation of intermediate, 6-fluoro-3,4- dihydro-2H-1-benzopyran-2-carboxaldehyde of Formula – II, converting the 6- fluoro-3,4-dihydro-2H-1-benzopyran-2-carboxaldehyde of Formula – II into mixture of [R*(S*)]-6-fluoro-3,4-dihydro-2-oxiranyl-2H-1-benzopyran and [R*(R*)]-6-fluoro-3,4-dihydro-2-oxiranyl-2H-1-benzopyran of Formula-V and separation of diastereomers of (R*)-6-Fluoro-3,4-dihydro-2-((S*)-oxiran-2-yl)- 2H-benzopran by forming azeotrope.
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- Process for the preparation of nebivolol
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The present invention relates to a novel process for the synthesis of the Nebivolol product depicted in Scheme 1, comprised of a reduced number of high-yield steps, and characterized by the enzymatic resolution of the chroman ester precursor.
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Page/Page column
(2015/08/03)
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- A NEW METHOD FOR PRODUCING NEBIVOLOL HYDROCHLORIDE OF HIGH PURITY
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The invention relates to a process for producing Nebivolol hydrochloride, (formula I) comprising the steps of: provision of a protected Nebivolol hydrochloride of the general formula (II), with P being an amine protecting group, and hydrogenation of said protected Nebivolol hydrochloride yielding Nebivolol hydrochloride of the formula (I).
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Page/Page column 22
(2015/09/22)
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- A PROCESS FOR THE PREPARATION OF 6-FLUORO-3,4-DIHYDRO-2H-CHROMENE- 2-CARBALDEHYDE
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The present invention relates to a process for ihe preparation of 6-f!uoro-3,4-dihydro- 2H-chromene-2-carbaidehyde which is useful as an Intermediate in the synthesis of Nebivolol or its pharmaceutical acceptable salts.
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Page/Page column 9
(2014/08/06)
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- PROCESS FOR THE PREPARATION OF EPOXIDES AS INTERMEDIATES FOR THE SYNTHESIS OF NEBIVOLOL
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The present invention relates to a novel process of synthesis of epoxides, 6-fluoro-2- (oxiran-2-yl) chroman (Figure 1), intermediates for the synthesis of nebivolol, depicted in Scheme (1), enabling to obtain the above- mentioned epoxides in a racemic or semichiral form.
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- PROCESS FOR THE PREPARATION OF NEBIVOLOL
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The present invention relates to a novel process for the synthesis of the Nebivolol product depicted in Scheme 1, comprised of a reduced number of high-yield steps, and characterized by the enzymatic resolution of the chroman ester precursor.
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Page/Page column 22-23
(2012/07/28)
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- PREPARATION OF NEBIVOLOL
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Processes for the synthesis of pharmacologically active 2,2-iminobisethanol derivatives, e.g., 2H-1-benzopyran-2 methanol-α,α′-iminobis(methylene)]bis-[6-fluoro-3,4-dihydro-[2R*[R*[R*(S*)]]]], and their pharmaceutically acceptable salts.
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- PROCESS FOR THE PREPARATION OF NEBIVOLOL
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The present invention relates to a novel process for the synthesis of Nebivolol product represented in Scheme (1), comprised of a reduced number of high-yield steps, and characterized by the kinetic resolution of the two epoxide pairs diastereoisomeric therebetween (mixture 1), allowing to avoid complex chromatographic separations.
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- PROCESS FOR THE CONVERSION OF (2R)-6-FLUORO-2-[(2S)-OXIRAN-2-YL]-3,4-DIHYDRO-2H-CHROMENE TO (2R)-6-FLUORO-2-[(2R)-OXIRAN-2-YL]-3,4-DIHYDRO-2H-CHROMENE
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The present invention relates to a novel process for the conversion of (2R)-6-fluoro- 2-[(2S)-oxiran-2-yl]-3,4-dihydro-2H-chromene (formula lll-A) to (2R)-6-fluoro-2-[(2R)-oxiran- 2-yl]-3,4-dihydro-2H-chromene (formula lll-B). The compound of formula lll-
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- An improved process for the preparation of nebivolol hydrochloride
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The present invention provides an improved process for the synthesis of Nebivolol and its pharmaceutically acceptable salts, more particularly hydrochloride salt of formula (I). Invention involves one pot synthesis of Nebivolol from epoxy monomer, which proceeds stereo specifically in high yield, without isolation of benzylated Nebivolol intermediate or its purification and does not require an additional purification of final compound.
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Page/Page column 8
(2010/04/24)
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- PROCESS FOR ISOLATION OF A MIXTURE OF RRRS AND SSSR CONFIGURATIONS OF NEBIVOLOL INTERMEDIATES
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The invention discloses a process for isolation of a mixture of RRRS and SSSR configurations of nebivolol intermediates represented by formulae II and III respectively, which is optionally selected from one of the following two manners: (1) precipitation solvent is added to alcohol solvent comprising the mixture of RRRS, SSSR, RRSR and SSRS configurations of nebivolol intermediates represented by formula I, heating, cooling to precipitate crystals and filtrating; (2) the mixture of RRRS, SSSR, RRSR and SSRS configurations of nebivolol intermediates represented by formula I is added into the mixture solvent of alcohol solvent and precipitation solvent, heating, cooling to precipitate crystals and filtrating. In formulae I, II and III, X is H, C1-C6 alkyl or C1-C6 alkoxy, n is 1-5.
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Page/Page column 9
(2010/10/19)
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- PROCESS FOR PREPARING NEBIVOLOL
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The present invention relates to a process for preparing Nebivolol and, more particularly, to an improved method of debenzylation of a compound of formula (II) useful for preparing nebivolol endowed with high purity.
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Page/Page column 12-13
(2010/05/14)
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- PROCESS FOR ISOLATION OF DESIRED ISOMERS OF NEBIVOLOL INTERMEDIATES
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The present invention relates to a simple and commercially viable process for separation of desired isomers of nebivolol intermediates from a mixture containing undesired isomers of nebivolol intermediates. Thus, (+)-[2R*[1S*,5S*(S*)]]+[2R*[1S*,5R*(R*)]]-α,α′-[phenylmethyliminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] is dissolved in diisopropyl ether at reflux temperature and cooled to below about 30° C. to obtain the desired (+)-[2R*[1S*,5S*(S*)]]-α,α′-[phenylmethyliminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol].
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Page/Page column 4
(2009/04/24)
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- Process for the Production of Nebivolol
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The subject of the invention is a process for the production of the racemic active ingredient nebivolol, in which diastereomeric cyanohydrins are produced, separated, and the separated diastereomers are coupled to one another after a transformation, preferably a partial or complete reduction of the cyano group or a Pinner saponification.
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Page/Page column 5
(2008/12/08)
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- PROCESS FOR PREPARING NEBIVOLOL
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The present invention relates to a process for preparing Nebivolol and, more particularly, to an improved process for synthesizing enantiomerically enriched 6-fluoro chroman alcohol or epoxide derivatives of formula, wherein R and X is defined in the description; as useful intermediates in the preparation of Nebivolol.
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Page/Page column 27
(2008/12/06)
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- A process for preparation of racemic nebivolol
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A process of making racemic [2S*[R*[R*[R*]]]] and [2R*[S*[S*[S*]]]]-(±)α,α'-[iminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] of the compound of the formula (I) and its pure [2S*[R*[R*[R*]]]]- and [2R*[S*[S*[S*]]]]- enantiomer comp
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Page/Page column 60; 44
(2008/06/13)
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- PROCESS FOR ISOLATION OF DESIRED ISOMERS OF NEBIVOLOL INTERMEDIATES
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The present invention relates to a simple and commercially viable process for separation of desired isomers of nebivolol intermediates from a mixture containing undesired isomers of nebivolol intermediates. Thus, (+)-[2R*[1S*,5S*(S*)]]+[2R*[1S*,5R*(R*)]]-α,α'- [phenylmethyliminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] is dissolved in diisopropyl ether at reflux temperature and cooled to below 30°C to obtain the desired(+)-[2R*[1S*,5S*(S*)]]-alfa,alfa'-[phenylmethyliminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H- 1-benzopyran-2-methanol].
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Page/Page column 7
(2008/06/13)
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- Process for preparation of racemic Nebivolol
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A process of making racemic [2S*[R*[R*[R*]]]] and [2R*[S*[S*[S*]]]]-(±)α,α′-[iminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] of the compound of the formula (I) and its pure [2S*[R*[R*[R*]]]]- and [2R*[S*[S*[S*]]]]-enantiomer compo
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- NEBIVOLOL AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS, PROCESS FOR PREPARATION AND PHARMACEUTICAL COMPOSITIONS OF NEBIVOLOL
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The present invention provides an improved process for the synthesis of nebivolol or its pharmaceutically acceptable salts, more particularly hydrochloride salt of formula (I). The present invention further provides a new Form T1 of nebivolol and its pharmaceutically acceptable salts. The present invention also provides pharmaceutical compositions and process for the preparation of a solid oral dosage form of nebivolol hydrochloride of formula (I), without the use of wetting agent, and optionally using binder and /or disintegrant.
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Page/Page column 36-37
(2010/10/20)
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- A NOVEL PROCESS FOR PREPARATION OF NEBIVOLOL INTERMEDIATES
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The present invention relates to a process for separation of desired diastereomeric pair from a mixture of diastereomeric pairs thereby obtaining nebivolol intermediates. Thus, the mixture of (+)-[1S*(R*)]-6-fluoro-3,4-dihydro-α-[[(phenylmethyl)amino]methyl]-2H-1-benzopyran-2-methanol, (+)-[1S*(S*)]-6-fluoro-3,4-dihydro-2-oxiranyl-2H-1-benzopyran and ethanol is heated to reflux temperature and stirred for 8 hours at the same temperature to obtain (+)-[2R*[1S*,5S*(S*)]]+[2R*[1S*,5R*(R*)]]-α,α'-[phenylmethyliminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol]. Then the reaction mass is cooled to 10oC, the pH is adjusted to 2 with HCl gas and stirred for 45 minutes at 25oC to 30oC. Then the separated solid is filtered and dried to give (+)-[2R*[1S*,5S*(S*)]]-α,α'-[phenylmethyliminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2- methanol] hydrochloride salt, which can be converted into nebivolol.
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Page/Page column 9
(2008/06/13)
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- NEW PROCESS FOR THE PREPARATION OF RACEMIC ([2S[2R*[R[R*]]]] and ([2R[2S*[S[S*]]]]-(±)- α,α' -[imino-bis(methylene)]bis[6-fluoro-chroman-2-methanol] AND ITS PURE [2S[2R*[R[R*]and
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Process for the preparation of racemic ([2S[2R*[R[R*]]]]- and ([2R[2S*[S[S*]]]]-(±)- α,α' -[imino-bis(methylene)]bis[6-fluoro-chroman-2-methanol] of the compound of the formula (I) and its pure ([2S[2R*[R[R*]]]]- and ([2R[2S*[S[S*]]]]- enantiomer compounds characterized in that the products are prepared from 4--fluoro-phenole or 4-fluoro-anisole via crystalline, optically active intermediates.
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- Enantioselective total synthesis of the antihypertensive agent (S,R,R,R)-Nebivolol
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The total synthesis of (S,R,R,R)-Nebivolol, a hypertensive agent, is reported. Claisen rearrangement and a one-pot Sharpless asymmetric epoxidation, intramolecular epoxide opening with internal phenoxide anion to generate the chiral chromane are the key s
- Chandrasekhar,Venkat Reddy
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p. 6339 - 6344
(2007/10/03)
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- Zr-catalyzed kinetic resolution of allylic ethers and mo-catalyzed chromene formation in synthesis. Enantioselective total synthesis of the antihypertensive agent (S,R,R,R)-nebivolol
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The first enantioselective total synthesis of the antihypertensive agent (S,R,R,R)-nebivolol (3) is described. The synthesis includes the efficient (EBTHI)Zr-catalyzed kinetic resolutions of cycloheptenyl styrenyl ethers 8 and 16, which are subsequently t
- Johannes, Charles W.,Visser, Michael S.,Weatherhead, Gabriel S.,Hoveyda, Amir H.
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p. 8340 - 8347
(2007/10/03)
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- Compositions containing micronized nebivolol
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The present invention relates to pharmaceutical compositions containing as active ingredient micronized nebivolol of formula (I) and ways of preparing said compositions. STR1
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