Gutron,Hormonchemie,W. Germany,1977
ChEBI: An aromatic ether that is 1,4-dimethoxybenzene which is substituted at position 2 by a 2-(glycylamino)-1-hydroxyethyl group. A direct-acting sympathomimetic with selective alpha-adrenergic agonist activity, it is used (generally as its hydro
hloride salt) as a peripheral vasoconstrictor in the treatment of certain hypotensive states. The main active moiety is its major metabolite, deglymidodrine.
19.5 parts of carbobenzoxyglycine, 7.1 parts of triethylamine and 162 parts ofdry toluene are mixed with 11.2 parts of isovaleric acid chloride at 0°C toform the mixed anhydride and the mixture is agitated for two hours at 0°C.32.4 parts of 1-(2',5'-dimethoxyphenyl)-2-aminoethanol-(1) are then added,the mixture is agitated for four hours at a temperature between 0°C and+10°C and then left to stand overnight at that temperature. A thick crystalpaste forms. The reaction product is dissolved in 450 parts of ethyl acetateand 200 parts of water. The ethyl acetate solution is separated, washed withhydrochloric acid, sodium bicarbonate solution and water, dried over sodiumsulfate and inspissated. The inspissation residue is digested with 342 parts ofxylene, the required product crystallizing out. 34.9 parts of 1-(2',5'-dimethoxyphenyl)-2-(N-carbobenzoxyglycineamido)-ethanol-(1) are obtained.66.2 parts of 1-(2',5'-dimethoxyphenyl)-2-(N-carbobenzoxyglycineamido)-ethanol-(1) are hydrogenated in the presence of 6.6 parts of palladium carbon(10%) in 2,000 parts of glacial acetic acid. When no more hydrogen isabsorbed (3 mols of hydrogen are used), hydrogenation stops. The catalyst isremoved by suction and the equivalent quantity of hydrochloric acid in ethanolis added to the filtrate with agitation. During further agitation at roomtemperature 28.6 parts of crude 1-(2',5'-dimethoxyphenyl)-2-glycineamidoethanol-(1)hydrochloride crystallize, and are isolated andrecrystallized from water-methanol for purification. 22.1 parts of pure productare obtained with a melting point of 192°C to 193°C.
An alternative synthesis route is described by Kleeman and Engel.
Orvaten (UpsherSmith); Proamatine (Shire).
Peripheral vasotonic, Antihypotensive
