cas 876514-31-7, (2R)-rel-6-Fluoro-3,4-dihydro-2-(2R)-2-oxiranyl-2H-1-benzopyran

Articles about 876514-31-7Total 30 be found

Article title
Article abstract
Author
Journal number and time
Download

Preparation method and application of Smo inhibitor based on Nebivolol
The invention discloses a preparation method and an application of a Smo inhibitor based on Nebivolol. The structural formula of the Smo inhibitor is as shown in a formula (I). The invention further discloses a synthetic method and an application of the Smo inhibitor. According to the Smo inhibitor, a beta-receptor retardant Nebivolol with inhibitory activity for Smo proteins serves as a lead compound, and optimization reconstruction is implemented based on the beta-receptor retardant Nebivolol to obtain the Smo inhibitor with good inhibitory activity.
-
(2019/10/17)

PROCESS FOR THE SYNTHESIS OF INTERMEDIATES OF NEBIVOLOL
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
-
Page/Page column 29-32

(2017/08/20)

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates
While the exploitation of the Sharpless asymmetric dihydroxylation as the source of chirality in the synthesis of acyclic molecules and saturated heterocycles has been tremendous, its synthetic utility toward chiral benzo-annulated heterocycles is relatively limited. Thus, in the search for wider applications of Sharpless asymmetric dihydroxylation-derived diols for the synthesis of benzo-annulated heterocycles, we report herein our studies in the asymmetric synthesis of (R)-1-((R)-6-fluorochroman-2-yl)ethane-1,2-diol, (R)-1-((S)-6-fluorochroman-2-yl)ethane-1,2-diol and (S)-6-fluoro-2-((R)-oxiran-2-yl)chroman, which have been used as late-stage intermediates for the asymmetric synthesis of the antihypertensive drug (S,R,R,R)-nebivolol. Noteworthy is that a large number of racemic and asymmetric syntheses of nebivolol and their intermediates have been described in the literature, however, the Sharpless asymmetric dihydroxylation has never been employed as the sole source of chirality for this purpose.
Devi, Runjun,Das, Sajal Kumar
supporting information
p. 571 - 578
(2017/03/29)

A process for the preparation of nebivolol and wherein the intermediate compound
The invention discloses a preparation method of nebivolol used for preparing medicines for treating hypertension of slight or medium degrees, and an intermediate compound. The preparation method comprises the following steps: taking 6-fluoro-2-(1-hydroxy-2-paratoluensulfonyl oxygroup-ethyl)-3,4-dihydrobenzopyrans as an initial raw material, introducing amino, then coupling with 6- fluoro-3,4-dihydro-2-epoxy ethyl-2H-1-benzopyran, and preparing (S,R,R,R) and (R,S,S,S)-nebivolol. Compared with a prior art, the preparation method has the advantages of novel design, simple operation and high yield, the usage of hazardous reagent such as ssodium azide and sodium hydride can be avoided, a column chromatography purifying method is avoided, so that the preparation method conforms to industrial production.
-
(2016/11/17)

Preparation of 6-fluoro -3,4-dihydro -2H-1-benzopyran-2-oxirane improved method
The invention relates to an improvement method for preparing a nebivolol key intermediate, namely 6-fluorin-3,4-dihydro-2H-1-benzopyranyl-2-epoxy ethane. The method comprises the following steps of: (a) condensing a compound (IV) and dihalogenated methane in the presence of an organic metal lithium compound to obtain a compound (II); (b) reducing the compound (II) to obtain a compound (III); and (c) performing cyclization on the compound (III) under alkaline condition to obtain a compound (I). The scheme of the invention has the advantages of readily available raw materials, easiness in operating, greatly increased reaction yield and purity and high contribution to industrial mass production.
-
Paragraph 0068; 0069; 0070

(2016/10/07)

Method for preparing nebivolol hydrochloride epoxy intermediate 6-fluoro-2-epoxy ethyl chroman
The invention discloses a method for preparing a nebivolol hydrochloride epoxy intermediate 6-fluoro-2-epoxy ethyl chroman. The method includes the following steps that firstly, under the conditions that water, phosphate, inorganic alkali B1, zinc chloride, a hydrogen source, aldose reductase and NADPH exist, the temperature is 30-70 DEG C and the pH value is 6.0-8.0, a reduction reaction happens to 2-chloro-1-(6-fluorochromane-2-yl)-ethanon, and 2-chloro-1-(6-fluorochromane-2-yl)-alcohol is obtained; secondly, 2-chloro-1-(6-fluorochromane-2-yl)-alcohol is heated in a C1-C6 alkanol solvent and inorganic alkali B2 for a reflux reaction, an organic ester solvent is added dropwise for crystallization after the reaction ends, and 6-fluoro-2-epoxy ethyl chroman is obtained. The preparation method is mild in reaction condition, raw materials and solvents are easy to obtain, and the method is suitable for industrial production.
-
Paragraph 0045

(2016/12/22)

A kind of nebivolol hydrochloride synthetic method
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.
-
(2017/03/28)

PROCESS FOR PREPARATION OF NEBIVOLOL AND IT'S SALTS
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.
-
Page/Page column 14; 15

(2016/12/07)

A PROCESS FOR THE PREPARATION OF 6-FLUORO-3,4-DIHYDRO-2H-CHROMENE- 2-CARBALDEHYDE
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.
-
(2014/08/06)

PROCESS FOR THE PREPARATION OF EPOXIDES AS INTERMEDIATES FOR THE SYNTHESIS OF NEBIVOLOL
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.
-
Page/Page column 23

(2013/03/26)

PROCESS FOR PREPARING NEBIVOLOL
The present invention relates to a process for preparing Nebivolol and, more in particular, to a fractional distillation method of a mixture of stereoisomers of formula intermediates useful in the preparation of nebivolol.
-
Page/Page column 4; 5

(2012/05/07)

PROCESS FOR THE PREPARATION OF NEBIVOLOL
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.
-
(2012/07/28)

PROCESS FOR PREPARING NEBIVOLOL
The present invention relates to a process for preparing Nebivolol and, more in particular, to a fractional distillation method of a mixture of stereoisomers of formula intermediates useful in the preparation of nebivolol.
-
Page/Page column 11-12

(2011/02/24)

PROCESS FOR THE PREPARATION OF NEBIVOLOL
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.
-
Page/Page column 14

(2011/09/15)

METHOD FOR PREPARING NEBIVOLOL
The present invention relates to a process for the preparation of nebivolol and, more particularly, to an improved process of synthesizing an alpha-haloketone of formula a key intermediate in the preparation of nebivolol.
-
Page/Page column 7

(2011/10/12)

PREPARATION OF NEBIVOLOL
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.
-
(2011/10/19)

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
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-
-
Page/Page column 9

(2011/11/06)

PROCESS FOR PREPARING NEBIVOLOL
The present invention relates to a process for preparing Nebivolol and, more particularly, to a method for stereoselective reduction of an alpha-haloketone of formula (I): intermediate useful for the preparation of Nebivolol.
-
Page/Page column 13

(2009/10/30)

PROCESS FOR PREPARING NEBIVOLOL
The present invention relates to a process for the preparation of Nebivolol and, more particularly, to an improved method of synthesizing 6-fluoro chroman epoxides of formula (I) key intermediates in preparing nebivolol.
-
Page/Page column 14

(2008/06/13)

PROCESS FOR PREPARING NEBIVOLOL
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.
-
Page/Page column 25-26

(2008/12/06)

PROCESS FOR PREPARING NEBIVOLOL
The present invention relates to a process for preparing nebivolol and, more particularly, to a process for preparing d-nebivolol and its enantiomer /-nebivolol or acid addition salts thereof starting from commercially available or easily obtainable 2,2-dimethyl-l,3 dioxolane-4- carbaldehyde and a vinyl Grignard reagent.
-
Page/Page column 30

(2008/12/06)

Sulfoxide-directed stereocontrolled access to 2H-chromans: Total synthesis of the (S,R,R,R)-enantiomer of the antihypertensive drug nebivolol
A homochiral sulfoxide-directed reductive deoxygenation of 2-(p-tolylsulfinyl)methyl-2-chromanols allows the stereoselective formation of 2H-chromans with up to 95:5 diastereoisomeric ratio. This new methodology was applied in a short and convergent enantioselective synthesis of the (S,R,R,R)-enantiomer of the antihypertensive drug Nebivolol. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
Carreno, M. Carmen,Hernandez-Torres, Gloria,Urbano, Antonio,Colobert, Francoise
supporting information; experimental part
p. 2035 - 2038
(2009/04/04)

Asymmetric-catalysed preparation and stereochemistry of (R,R)-,(S,R)-(6-fluoro-2-chromanyl)-1,2-ethanediol
(R,R)-,(S,R)-1-(6-fluoro-2-chromanyl)-1,2-ethanediol 1a/1b were prepared by hydrolytic kinetic resolution (HKR) of terminal racemic epoxides using (R,R)-SalenCo(OAc) as a catalyst. Their configurations were established by comparison with two authentic samples by HPLC.
Yang, Yun-Xu,Liu, Shi-Xiang
p. 506 - 508
(2008/09/21)

Process for preparation of racemic Nebivolol
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
-
(2008/06/13)

A process for preparation of racemic nebivolol
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
-
Page/Page column 55; 56-57; 38; 46

(2008/06/13)

Hydroxylated nebivolol metabolites
Hydroxylated nebivolol metabolites increase NO release from human endothelial cell preparations in a concentration dependent fashion following acute administration. In addition, hydroxylated nebivolol metabolites, including but not limited to 4-hydroxy-6,6′difluoro-, 4-hydroxy-5-phenol-6,6′difluoro-, and 4-hydroxy-8-pheno-6,6′difluoro-, have the ability to increase the capacity for NO release in human endothelial cells following chronic administration. This invention provides hydroxylated nebivolol metabolites and compositions comprising nebivolol and/or at least one hydroxylated metabolite of nebivolol and/or at least one additional compound used to treat cardiovascular diseases or a pharmaceutically acceptable salt thereof. In addition, this invention provides methods of treating and/or preventing vascular diseases by administering at least one hydroxylated metabolite of nebivolol that is capable of releasing a therapeutically effective amount of nitric oxide to a targeted site affected by the vascular disease. Also, this invention is directed to the treatment and/or prevention of migraine headaches administering at least one hydroxylated metabolite of nebivolol. This invention may also be used in conjunction with or as a single treatment of metabolic syndrome disorders.
-
Sheet 10

(2010/11/25)

NEBIVOLOL AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS, PROCESS FOR PREPARATION AND PHARMACEUTICAL COMPOSITIONS OF NEBIVOLOL
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.
-
Page/Page column 16-17; 33-34

(2010/10/20)

A mild synthesis of α,α′-[iminobismethylene]bis[6-fluoro- 3,4-dihydro-2H-1 -benzopyran-2-methanol]
A new synthesis of α,α′-[iminobismethylene]bis[6-fluoro- 3,4-dihydro-2H-1-benzopyran-2-methanol (1) is described, with most reactions being carried out at room temperature and normal pressure, that will further contribute to the development of new scalable synthesis of the related drug substance of Nebivolol (overall yield: 33%).
Bai, Yihui,Chen, Xinzhi
p. 807 - 808
(2007/10/03)

Method of lowering the blood pressure
A method of potentiating the effects of blood pressure reducing agents in warm-blooded animals, said method comprising administering to said warm-blooded animals of an effective amount of a blood pressure reducing agent and a 2,2′-iminobisethanol derivative.
-
(2008/06/13)

Enantioselective total synthesis of the antihypertensive agent (S,R,R,R)-Nebivolol
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
p. 6339 - 6344
(2007/10/03)