119365-25-2

Basic information

• Product Name: R 74714
• Synonyms: R 74714;Nebivolol impurity B
• CAS NO: 119365-25-2
• Molecular Formula: C22H25F2NO4
• Molecular Weight: 405.4350064
• Mol File: 119365-25-2.mol
• Article Data: 25

Chemical Properties

• Appearance: /
• CAS DataBase Reference: R 74714(CAS DataBase Reference)
• NIST Chemistry Reference: R 74714(119365-25-2)
• EPA Substance Registry System: R 74714(119365-25-2)

Safety Data

• Hazardous Substances Data: 119365-25-2(Hazardous Substances Data)

Usage

Uses

R 74714 is a potential agonist and blocker of the β2 adrenergic receptor and have been profiled as an isomer of Nebivolol (N387900), an antihypertensive agent.

Upstream product

• 303176-42-3 (R)-2-amino-1-[(S)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]ethanol 
• 303176-46-7 (R)-2-[(R)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]-2-hydroxyethyl-4-methylbenzenesulfonate 
• 371-41-5 4-Fluorophenol 
• 9920-09-6 α,α'-iminobis(methylene)bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] hydrochloride 
• 929706-85-4 (+/-)-[2R*[1S*,5S*(S*)]]-α,α-[phenylmethyliminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] 
• 129050-27-7 (S*,R*)-(±)-α-[(benzylamino)methyl](6-fluoro-2-chromanyl)methanol 
• 929706-85-4 α,α'-[[(phenylmethyl)imino]bismethylene]bis-[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] 
• 905454-41-3 2-amino-1-[6-fluoro-(2R)-3H,4H-2-chromenyl]-(1S)-ethan-1-ol 
• 197706-50-6 6-fluoro-(2R)-2-[(2R)-2-oxiranyl]-3,4-dihydrobenzopyran 
• 129050-26-6 (2R)-6-fluoro-2-[(2S)-oxiran-2-yl]-3,4-dihydro-2H-chromene 
• 99199-90-3 6-fluoro-3,4-dihydro-2-oxiranyl-2H-1-benzopyran 
• 409346-73-2 6-fluoro-3,4-dihydro-2H-1-benzopyran-2-carboxaldehyde 
• 99199-62-9 6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol 
• 99199-60-7 6-fluoro-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid 

Downstream Products

• 169293-50-9 nebivolol hydrochloride 
• 152520-56-4 nebivolol hydrochloride 
• 9920-09-6 α,α'-iminobis(methylene)bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] hydrochloride 
• 920299-33-8 (R)-1-((R)-6-Fluoro-chroman-2-yl)-2-[(S)-2-((R)-6-fluoro-chroman-2-yl)-2-hydroxy-ethylamino]-ethanol; hydrochloride 
• 152520-56-4 DL-nebivolol hydrochloride 

Relevant articles and documents

Synthesis of intermediate compound and [...] (by machine translation)

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)

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.

METHOD FOR PRODUCING NEBIVOLOL

The present invention relates to a method for producing racemic nebivolol represented by general formula (I) from the enantiomerically-pure compounds represented by formula (IVa) and (IVb); whereby racemic nebivolol is obtained through mixing enantiomerically-pure d-nebivolol and l-nebivolol which are synthesised independent of each other as enantiomerically-pure compounds through individual coupling of the 4 enantiomerically-pure key intermediates represented by formula (IIa-d) to the corresponding precursors represented by formula (IIIa-d); whereby d-nebivolol (Ia) is obtained through coupling (IIa) to (IIIb) or (IIb) to (IIIa) and l-nebivolol (Ib) is obtained through coupling (IIc) to (IIId) or (IId) to (IIIc), and PG in the intermediates represented by formula (IIa-d) is a hydrogen atom or an amine protection group, and X in the precursors represented by formula (IIIa-d) is a halogen atom, a hydroxyl group, an acyl group, an alkylsulfonyloxy group or an arylsulfonyloxy group, whereby intermediate (IIa) is formed from (IIIa), intermediate (IIb) is formed from (IIIb), intermediate (IIc) is formed from (IIIc), and intermediate (IId) is formed from (IIId), whereby the precursors represented by formula (IIIa) and (IIId) originate from the ketone precursor represented by formula (IVa), and the precursors represented by formula (IIIb) and (IIIc) originate from the ketone precursor represented by formula (IVb), and Z in the ketone precursors (IVa,b) is a halogen atom, a hydroxyl function, an acyl group, an alkylsulfonyloxy group or an arylsulfonyloxy group.