Patent GB-1006588-A (GB)
Title: N-substituted-1-phenyl-2-aminopropanes
Inventor: STEIT CORNELIUS VAN DER
IPC: C07C57/50
Filed: 1962-10-19
Abstract: The invention comprises compounds of the formula <FORM:1006588/C2/1> wherein X1 and X each represent a hydrogen atom or together represent a single bond between the two carbon atoms, Y represents a single bond or an oxygen or sulphur atom or the group = NR2 (R2 representing a C1- 6 alkyl group or a hydrogen atom) or a -CH2-CH2- or -CH = CH- group and R1 represents a hydrogen or halogen atom or a C1- 6 alkyl group, and the non-toxic acid addition salts thereof.  The preferred compounds are those in which X1, X, and R1 are hydrogen atoms.  The compounds are prepared by a variety of methods (a) by condensing 1-phenyl-2-amino-propane with an aldehyde of the formula <FORM:1006588/C2/2> and reducing the azomethine bond in the resultant amino compound of the formula <FORM:1006588/C2/3> and, when X1 and X represent a single bond, optionally hydrogenating the double bono -CH = C<; the condensation may be affected under reducing conditions to give the amind compound directly; (b) by heating of 1-phenyl-2-amino-propane with an acid of the formula <FORM:1006588/C2/4> or the acid halide thereof, and reducing the carbonyl group of the resultant amide of the formula <FORM:1006588/C2/5> to a methylene group; (c) by reductive condensation of phenylacetone and an amine of the formula <FORM:1006588/C2/6> and (d) by the reaction of a compounds <FORM:1006588/C2/7> with a compound <FORM:1006588/C2/8> wherein one of A and B represents a primary amino group and the other represents a halogen atom.  Examples describe the preparation of N - [2(10,11 - dihydro - 5H - dibenzo - [a,d]-cycloheptens - 5 - yl) - ethyl]-, N - [2 - (fluoren-9 - yl) - ethyl]-, N - [2 - (5H - dibenzo - [a,d]-cyclohepten - 5 - yl) - ethyl]-, N - [2 - (xanthen-9 - yl) - ethyl]-, N - [2 - (thioxanthen - 9 - yl)-ethyl]-and N - [2 - (9,19 - dihydro - 10 - methyl-acridin - 9 - yl) - ethyl] - 1 - phenyl - 2 - amino-propanes. A number of compounds of the above type wherein R1 is a C1- 6 alkyl, chloro and bromo group are specified.  Aldehydes of the formula II may be prepared by condensing a ketone of the formula <FORM:1006588/C2/9> with acetylene to give the alcohol of the formula <FORM:1006588/C2/100> followed by isomerization in the presence of an acid.  The aldehydes II may also be obtained by hydrolysis of the corresponding dialkylacetal.  Carboxylic acids of the formula VIII are obtained by oxidation of the corresponding aldehyde II or, where X and X1 are hydrogen, by reacting an alcohol of the formula <FORM:1006588/C2/111> with malonic acid to yield a compound <FORM:1006588/C2/122> which is decarboxylated to the mono-acid by heating.  The invention includes pharmaceutical compositions comprising at least one of the compounds of formula I, or a non-toxic acid addition salt thereof, which exhibit a dilating activity on the coronary blood vessels and which may be administered orally or parentally in the form of, e.g. tablets, pills, capsules, suspensions, emulsions, syrups, elixirs or unjectable preparations. Example 9 describes a composition in tablet form.