Bevantolol
hydrochloride,Parke, Davis
(Pfizer)
ChEBI: Bevantolol is a propanolamine that is 3-aminopropane-1,2-diol in which the hydrogen of the primary hydroxy group is substituted by 3-methylphenyl and one of the hydrogens attached to the nitrogen is substituted by 2-(3,4-dimethoxyphenyl)ethyl. A beta1 adrenoceptor antagonist, it has been shown to be as effective as other beta-blockers for the treatment of angina pectoris and hypertension. It has a role as a beta-adrenergic antagonist, a calcium channel blocker, an antihypertensive agent and an anti-arrhythmia drug.
To a solution of 50 g (1.25 mol) of NaOH in 1200 ml H2O was added 108 g (1
mol) of m-cresol freshly distilled and at 15°C in one lot 117ml (1.5 mol) of
epichlorohydrin. The emulsion was stirred at room temperature for 16 hours in
a creased flask. The product was taken up in 1000 ml of toluene and washed
with 500 ml water. Distillation yielded 135.7 g=82% of 3-(m-tolyloxy)-1,2-
epoxypropane, b.p. 61°C at 0.05 mm.
Preparation of bevantolol hydrochloride:
To a suitable reactor under a nitrogen blanket is added 13.7 kg of β-(3,4-
dimethoxyphenyl)ethylamine. The amine is cooled to 5°C and 12.5 kg of 3-
(m-tolyloxy)-1,2-epoxypropane is added maintaining the temperature between
5-10°C. After 10 hours, the mixture is seeded with bevantolol free base;
seeding is repeated approximately every 2 hours until it is evident that
crystallization has started. After stirring for 48 hours at 10°C, 26 L of hexane
is added. The temperature is raised to 25°C and stirring is continued for 48
hours. The slurry is filtered and the collected solid is dried under vacuum. The
product is dissolved in 60 L of isopropyl alcohol and the solution is filtered.
The reactor and filter are rinsed with 186 L of isopropyl alcohol and 2.7 kg of
anhydrous hydrogen chloride is added to the combined filtrate. The batch is
heated to reflux for 2 hours. The temperature is adjusted to 65°C and the
solution is seeded with bevantolol hydrochloride crystals. The mixture is held
at this temperature with stirring until a heavy sand-like slurry is present. The
mixture is allowed to cool to ambient temperature without stirring or artificial
cooling. It is then cooled to 20°C. The slurry is centrifuged and the product
rinsed with isopropyl alcohol until the filtrate is colorless. After being vacuum
dried at 50-55°C the product is milled if necessary; yield of bevantolol
hydrochloride 22.7 kg (78.6%); melting point 137-138°C.
Antiarrhythmic, Beta-adrenergic blocker
This antihypertensive agent (FW = 345.43 g/mol; CAS 59170-23-9), also known by the code name NC-1400 and systematically as (RS)-[2-(3,4- dimethoxyphenyl)ethyl]-[2-hydroxy-3-(3-methylphenoxy)propyl]amine, is a dual-action b-blocker and calcium ion channel blocker. Bevantolol is a selective b1-adrenoceptor blocker with some blocking activity of a1- adrenoceptors.
