| abstract |
The present invention provides an improved synthesis method of nebivolol or a pharmaceutically acceptable salt, particularly a hydrochloride of the following formula (I), useful for the treatment and prevention of coronary vascular diseases. An improved synthesis method of nebivolol reduces the unnecessary isomer impurities, develops a method of synthesizing a desired high-purity diastereomeric mixture, and at the same time, processes for nebivolol synthesis without using harmful sodium hydride. A method with fewer steps. That is, 6-fluoro-3,4-dihydrobenzopyran-2-aldehyde is converted to an oxirane group in the presence of potassium tert-butoxide, and then the benzylated form of the compound is reacted with the compound. A method for producing a salt represented by the above formula (I) via a benzylated nebivolol base. A pharmaceutical composition prepared using nebivolol as an active ingredient and not using a wetting agent exhibits excellent solubility. In addition, a new amorphous form of nebivolol, designated as Form T1, and a pharmaceutically acceptable salt is also described. [Selection figure] None |