Alprenolol Hydrochloride

8-Chloro-1 -methyl-6-phenyl4H-s-triazolo-[4,3-a] [1,4] -benzodiazepine A stirred suspension of 5-chloro-2-[3-(bromomethyl)-5-methyl4H-1,2,4-triazol4-yl] -benzophenone (391 mg, 0.001 mol) in tetrahydrofuran (15 ml) was cooled in an ice-bat hand treated with a saturated solution of ammonia in methanol (12.5 ml). The resulting solution was allowed to warm to ambient temperature and stand for 24 hours. It was then concentrated in vacuo. The residue was suspended in water, treated with a little sodium bicarbonate and extracted with methylene chloride. The extract was washed with brine, dried with anhydrous potassium carbonate and concentrated. The residue was crystallized from methylene chloride-ethyl acetate to give 

220 g of crude product of melting point 227°-228.5°C. Recrystallization of this material from ethyl acetate gave 0.142 g of melting point 228°-229.5°C of 8-chloro-1-methyl-6-phenyl-4H-s-triazolo[4,3-a [1,4] -benzodiazepine. 

Hester, J.B., Jr. U.S. Patent 3,681,343 August 1,1972 assigned to The Upjohn Company. Hester, J.B., Jr. U.S. Patent 3,781,289 December 25,1973 assigned to The Upjohn Company. Hester, J.B., Jr. U.S. Patent 3,709jS98 January 9,1973 assigned to The Upjohn Company. 

Chemical Name 1-[(1-Methylethyl)amino] -3-[2-(2-propenyl)phenoxy] -2-propanol Common Name — 

Trade Name Manufacturer Country Year Introd 

A solution of 24.6 g of o-allyl-epoxypropoxybenzene dissolved in 250 ml of absolute ethanol saturated with ammonia was placed in an autoclave and heated on a steam-bath for 2 hours. The alcohol was then removed by distillation and the residue was redissolved in a mixture of methanol and ethylacetate. Hydrogen chloride gas was introduced into the solution. The hydrochloride salt was then precipitated by the addition of ether to yield 11.4 g of product. Five grams of the amine-hydrochloride thus formed were dissolved in 50 ml of methanol and 9 ml of acetone. The resulting solution was cooled to about 0°C. At this temperature 5 g of sodium borohydride were added over a period of 1 hour. Another 2.2 ml of acetone and OS g of sodium borohydride were added and the solution was kept at room temperature for 1 hour, after which 150 ml of water were added to the solution. The solution was then extracted with three 100-ml portions of ether which were combined, dried over potassium carbonate, and evaporated. The free base was then recrystallized from petrol ether (boiling range 40°-60°C) to yield 2.7 g of material having a melting point of 57°C. 

The corresponding hydrochloride was prepared by dissolving 2 g of the product, prepared above, in 20 ml of acetone, and adding to the resulting solution acetone saturated with hydrogen chloride until the pH was reduced to about 3. The precipitated hydrochloride salt was then recrystallized from acetone. 

5-Chloro-2-[3-(bromomethyl)-6-methyl-4H-1,2,4-triazol-4-yl] -benzophenone A solution of 

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FIG. 17 Chemical structures of (a) epinephrine hydrochloride, (b) dopamine hydrochloride, (c) isoproterenol hydrochloride, (d) phenylephrine hydrochloride, (e) tolazoline hydrochloride, (f) oxyprenolol hydrochloride, (g) alprenolol hydrochloride, and (h) propranolol hydrochloride. 

Cl5H14N2O2, Bis(p-methoxyphenyl)carbodiimide, 44B, 31 Cl5H24CINO2, Alprenolol hydrochloride, 39B, 24 40B, 38 C15H24CINO3, Oxprenolol hydrochloride, 43B, 49 C16H21NO2, Propranolol, 43B, 45... 

Strom has reported data which can also serve as a helpful guide [55]. He determined the amount of l-(2-allylphenoxy)-3-isopropylaminopropan-2-ol (alprenolol) hydrochloride which was extracted from aqueous solution by several different solvents. 

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