929706-85-4

Basic information

• Product Name: rac N-Benzyl Nebivolol
• Synonyms: rac N-Benzyl Nebivolol;α,α'-[[(PhenylMethyl)iMino]bis(Methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-Methanol
• CAS NO: 929706-85-4
• Molecular Formula: C₂₉H₃₁F₂NO₄
• Molecular Weight: 495.5575464
• Product Categories: Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 929706-85-4.mol

Chemical Properties

• Appearance: /
• Solubility: Chloroform, Dichloromethane, Ethyl Acetate, Methanol
• CAS DataBase Reference: rac N-Benzyl Nebivolol(CAS DataBase Reference)
• NIST Chemistry Reference: rac N-Benzyl Nebivolol(929706-85-4)
• EPA Substance Registry System: rac N-Benzyl Nebivolol(929706-85-4)

Safety Data

• Hazardous Substances Data: 929706-85-4(Hazardous Substances Data)

Usage

Chemical Properties

Pale Brown Semi-Solid

Uses

Protected Nebivolol.

Upstream product

• 99199-90-3 6-fluoro-3,4-dihydro-2-oxiranyl-2H-1-benzopyran 
• 99199-91-4 6-fluoro-3,4-dihydro-α-[[(phenylmethyl)amino]methyl]-2H-1-benzopyran-2-methanol 
• 129050-27-7 (S*,R*)-(±)-α-[(benzylamino)methyl](6-fluoro-2-chromanyl)methanol 
• 793669-26-8 [1R*(R*)]-6-fluoro-3,4-dihydro-2-(oxiran-2-yl)-2H-chromene 
• 99199-91-4 (+/-)-[1S*(R*)]-6-fluoro-3,4-dihydro-α-[[(phenylmethyl)amino]methyl]-2H-1-benzopyran-2-methanol 
• 99199-90-3 (+/-)-[1S*(S*)]-6-fluoro-3,4-dihydro-2-oxiranyl-2H-1-benzopyran 
• 100-46-9 benzylamine 
• 99199-62-9 6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol 
• 409346-73-2 6-fluoro-3,4-dihydro-2H-1-benzopyran-2-carboxaldehyde 
• 99199-60-7 6-fluoro-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid 
• 99199-59-4 6-fluoro-4-oxo-4H-1-benzopyran-2-carboxylic acid 

Downstream Products

• 118457-14-0 R 67142 
• 118457-16-2 nebivolol 
• 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 nebivolol hydrochloride 
• 99200-09-6 (+/-)-[2R*[1S*,5S*(S*)]]-α,α-[iminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] 
• 169293-50-9 nebivolol hydrochloride 
• 9920-09-6 α,α'-iminobis(methylene)bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] hydrochloride 
• 99200-09-6 nebivolol 

Relevant articles and documents

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.

PROCESS FOR ISOLATION OF A MIXTURE OF RRRS AND SSSR CONFIGURATIONS OF NEBIVOLOL INTERMEDIATES

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.

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

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%).

A NOVEL PROCESS FOR PREPARATION OF NEBIVOLOL INTERMEDIATES

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.