Patent GB-993748-A (GB)
Title: 4-azaphenthiazine derivatives
IPC: C07D417/06
Filed: 1962-06-28
Abstract: The invention comprises compounds of the general formula <FORM:0993748/C2/1> wherein the benzene ring of the 4-azaphenthiazine residue may be substituted by a chlorine atom, Alk represent a straight or branched alkylene residue of 2-4 carbon atoms, and X represents the group-NR1R2 in which R1 and R2 are like or different and represent hydrogen atoms or C1-4 alkyl groups or are joined to form a heterocyclic ring or X represents the group OR in which R is a hydrogen atom or a C1-4 alkyl group, their acid addition and quaternary ammonium salts and the preparation thereof, wherein X is the group -NR1R2 by (a) heating an appropriate 10-unsubstituted 4-azaphenthiazine with a compound of the formula <FORM:0993748/C2/2> in the presence of a condensation agent splitting off hydrogen halide and in an inert solvent; or (b) heating an appropriate 10-unsubstituted azophenthiazine with a compound of the general formula <FORM:0993748/C2/3> under the conditions of (a) and reacting the carboxylic ester group with an appropriate amine; or (c) heating an appropriate 10-unsubstituted 4-azaphenthiazine with a compound of the formula <FORM:0993748/C2/4> under the conditions of (a) and converting the nitrile into a carboxylic acid amide group; or (d) heating a compound of the formula <FORM:0993748/C2/5> wherein the benzene ring may be substituted by a chlorine atom and in which R represents a C1-4-alkyl group and Y represents an anion, with a compound of the formula <FORM:0993748/C2/6> at from 100-200 DEG  C.; or (e) reacting a compound of the formula <FORM:0993748/C2/7> wherein the benzene ring may be substituted by a chlorine atom and Alk1 represents an alkylene group having one CH2 group less than the Alk group, or an acetate of such an aldehyde, with a piperidine carboxylic acid amide as in (d) in the presence of formic acid; or (f) reacting a compound of the formula <FORM:0993748/C2/8> wherein the benzene ring may be substituted by a chlorine atom, is reacted with a piperidine carboxylic acid amide, as in (d), with simultaneous catalytic hydrogenation in the presence of a noble metal catalyst in an alkali solution; or (g) reacting an appropriate 10-unsubstituted-4-azaphenthiazine with a piperidine carboxylic acid amide, as in (d), and a compound Cl-Alk-Br in the presence of a condensation agent splitting off hydrogen halide, optionally in the presence of an inert solvent or when X represents OR reacting an appropriate 10-unsubstituted 4-aza-phenthiazine with a compound of the formula <FORM:0993748/C2/9> in the presence of an inert solvent and in the presence of a condensation agent splitting off hydrogen halide.  1 - (3 - Bromopropyl) - nipecotinic acid diethyl amide is prepared by reacting nicotinic acid diethylamide with 3-chloro-1-propanol, hydrogenating the quaternary 3-hydroxypropyl-N-nicotinic acid diethylamide hydrobromide to 1 - (3 - hydroxypropyl) - nipecotinic acid diethylamide and reacting this with hydrobromic acid. 1 - (3 - Chloropropyl) - isonipecotinic acid dimethylamide, diethylamide and piperidide were prepared similarly through 1-(3-hydroxy-propyl)-isonipecotinic acid dimethylamide, diethylamide and piperidide and 1-(3-chloropropyl)-isonipecotinic acid ethyl ester through 1-3-hydroxypropyl)-isonipecotinic acid ethyl ester.