Patent GB-1381482-A (GB)
Title: Ureidophenoxyalkanolamine derivatives
Inventor: ECKARDT R
IPC: C07D303/22
Filed: 1971-12-15
Abstract: 1381482 Urea derivatives ARZNEIMITTELWERK DRESDEN VEB 15 Dec 1971 52957/71 Heading C2C The invention comprises urea derivatives of the Formula I wherein R 1  is an unbranched C 1-6  alkyl radical, a branched C 3-8  alkyl, C 3-6  alkenyl, C 3-6  alkynyl, or C 3-7  cycloalkyl, and R 2  is C 3-7  cycloalkyl, C 3-6  alkenyl, or C 3-6  alkynyl, the acid addition salts thereof and their preparation. They are prepared by (a) reacting the appropriate 1- (ureidophenoxy) - 2,3 - epoxypropanes with amines of the formula R 1 NH 2 , (b) by reacting the appropriate l-[alkoxy-(or phenoxy)-carbonylaminophenoxy]-2 -hydroxy - 3 - (R 1 -amino) propanes with amines of the formula R 2 NH 2 , (c) by reacting N-R 2 -N<SP>1</SP>-(hydroxyphenyl)- ureas with the corresponding (2,3-epoxypropyl)- R 1 -amines, (d) reacting 1-(amino-phenoxy)-2- hydroxy-3-(R 1 -amino) propanes with isocyanates of the formula R 2 NCO, (e) by reacting compounds of the above Formula I in which R 2  is H with amines of the formula R 2 NH 2 , (f) by hydrogenolysis of the appropriate 1-[(3- R2 - ureido)phenoxy] - 2 - hydroxy - 3 - (N- benzyl - N - R 1  - amino)propane, (g) reacting carbonyl compounds of the formula R 10 -COR 11 , wherein R 10  and R 11 , together with the connecting carbon atom represent a radical which can be converted by hydrogenation into an R 1  group, under reducing conditions with the appropriate 1-[(3-R 2 -ureido)phenoxy]-2-hydroxy - 3 - aminopropanes, (h) reacting the appropriate 1-[(3 - R 2  - ureido) - phenoxy] - 2- hydroxy - 3 - chloropropanes with amines of the formula R 1 NH 2 , (j) reacting the corresponding 1 - [(3 - R 2  - ureido)phenoxy] - 2 - hydroxy- 3-aminopropanes with halides of the formula R 1 X wherein X is Cl, Br or I, or (j) reacting the appropriate N - R 2  - N<SP>1</SP> - (hydroxyphenyl)ureas with 2 - phenyl - 3 - R 1  - 5 - chloromethyloxazolidine. Other methods are described in general terms. 2 - Phenyl - 3 - butyl - 5 - chloromethyloxazolidine is obtained by reacting benzal-butylamine and epichlorohydrin in the presence of anhydrous zinc chloride. 1 - (4 - Phenoxycarbonylaminophenoxy)- 2- hydroxy - 3 - t. - butylaminopropane hydrochloride is prepared by reacting phenyl chloroformate with 1-(4-aminophenoxy)-2-hydroxy-3- t. - butylaminopropane hydrochloride. N - R 2  - N<SP>1</SP> - [(2,3 - epoxypropoxy)phenyl]- ureas are obtained by reacting epichlorhydrin with the corresponding N-R 2 -N<SP>1</SP>-(hydroxyphenyl)ureas. 1 - [4 - (3 - Cyclohexylureido)phenoxy] - 2- hydroxy - 3 - (N - benzyl - N - t. - butylamino)- propane is prepared by reacting N-cyclohexyl- N<SP>1</SP> - [4 - (2,3 - epoxy - propoxy)phenyl]urea with N-benzyl-N-t.-butylamine. 1 - [4 - (3 - Cyclohexylureido)phenoxy- 2 - hydroxy - 3 - aminopropane hydrochloride is made by reacting ammonia with N-cyclohexyl-N<SP>1</SP>- [4-(2,3-epoxypropoxy)phenyl]urea. 1 - [4 - (3 - Cycloherylureido)phenoxy] - 2- hydroxy - 3 - chloropropane is obtained by reacting N - cyclohexy - N<SP>1</SP> - [4 - (2,3 - epoxypropoxy)phenyl]urea with hydrochloric acid. Pharmaceutical compositions having #-adrenergic blocking action, contain the above novel compound or acid addition salts thereof in admixture with solid or liquid pharmaceutical diluents or carriers.