99199-91-4

Upstream product

• 99199-90-3 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 
• 793669-26-8 [1R*(R*)]-6-fluoro-3,4-dihydro-2-(oxiran-2-yl)-2H-chromene 
• 793669-26-8 [1S*(R*)]-6-fluoro-3,4-dihydro-2-(oxiran-2-yl)-2H-chromene 
• 943126-76-9 C₁₂H₁₁FO₄ 
• 943126-67-8 (+/-)-5-[6-fluorochroman-2-carbonyl]-2, 2-dimethyl[1, 3]dioxane-4, 6-dione 
• 943126-70-3 (+/-)-3-(6-fluorochroman-2-yl)-3-oxo-propionic acid tert-butyl ester 
• 943126-72-5 2-chloro-1-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)ethan-1-one 
• 99199-60-7 6-fluoro-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid 
• 850896-51-4 nebulic acid chloride 
• 409346-73-2 6-fluoro-3,4-dihydro-2H-1-benzopyran-2-carboxaldehyde 
• 99199-90-3 (+/-)-[1S*(S*)]-6-fluoro-3,4-dihydro-2-oxiranyl-2H-1-benzopyran 
• 99199-59-4 6-fluoro-4-oxo-4H-1-benzopyran-2-carboxylic acid 

Downstream Products

• 929706-85-4 α,α'-[[(phenylmethyl)imino]bismethylene]bis-[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] 
• 99200-09-6 nebivolol 
• 929706-85-4 (+/-)-[2R*[1S*,5S*(S*)]]-α,α-[phenylmethyliminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] 
• 929706-85-4 (+/-)-[2R*[1S*,5R*(R*)]]-α,α-[phenylmethyliminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] 

Relevant academic research and scientific papers

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 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.

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%).

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.