HEXOPRENALINE SULPHATE

Originator

Etoscol,Byk Gulden,W. Germany,1973

The Uses of HEXOPRENALINE SULPHATE

Hexoprenaline acts as a β2-adrenoreceptor agonist/betamimetic and a vasoactive agent.

Manufacturing Process

The N,N'-dibenzyl-N,N'-bis-[2-(3',4'-dihydroxyphenyl)-2-oxoethyl]- hexamethylene-diamine dichlorohydrate-monohydrate used as the starting material was prepared as follows: 2 mols of chloroaceto pyrocatechin were dissolved in 2,000 cc of acetone and heated to boiling with 2 mols of N,N'- dibenzylhexamethylene-diamine for 12 hours, almost the theoretical quantity of N,N'-dibenzylhexamethylene-diamine dichlorohydrate being precipitated and removed by suction after cooling. Excess HCl was added to the filtrate, approximately 66% of the theoretically possible quantity of crude dichlorohydrate of the N,N'-dibenzyl-N,N'-bis-[2-(3',4'-dihydroxyphenyl)-2-oxoethyll-hexamethylene-diamine being precipitated. The product was cleaned by recrystallization from water with the addition of animal charcoal. After drying the substance contained water of crystallization at ambient temperature, MP 206° to 209.5°C.
Five grams of N,N'-dibenzyl-N,N'-bis[2-(3',4'-dihydroxyphenyl)-2-oxoethyl]- hexamethylenediamine dichlorohydrate as a monohydrate were hydrogenated under considerable agitation by means of 2.0 grams of 10% palladium-carbon, with hydrogen in a mixture of 270 cc of methanol and 50 cc of water at 45°C and normal pressure. After about 4 hours the theoretical quantity of hydrogen (4 mols of hydrogen per 1 mol of substance) was absorbed for the splitting off of the two benzyl radicals and the reduction of the two carbonyl groups to carbinol groups, and the hydrogenation came to a stop.
After separation of the catalyst the product was concentrated until dry, the residue was triturated with acetone, the resulting crystallizate was removed by suction and washed with acetone. The yield of N,N'-bis-2-(3',4'- dihydroxyphenyl)-2-hydroxyethyll-hexamethylene-diamine dichlorohydrate was 3.3 grams, i.e., 92% of the theoretical value. A quantity of 2.8 grams having a melting point of 197.5° to 198°C was obtained by precipitation from a mixture of methanol-ether.
Free N,N'-bis-[2-(3',4'-dihydroxyphenyl)-2-hydroxyethyl]-hexamethylenediamine can be separated from these salts by the addition of the equivalent quantity of caustic alkali solution. It has a melting point of 162° to 165°C and contains half a mol of water of crystallization.
N,N'-bis-[2-(3',4'-dihydroxyphenyl)-2-hydroxyethyl]-hexamethylenediaminesulfate (MP 222° to 228°C) can be obtained by reacting the base with the equivalent quantity of sulfuric acid in an alcohol solution, followed by concentration and precipitation from water-alcohol solution.

brand name

Delaprem (Savage).

Therapeutic Function

Bronchodilator