Patent GB-773183-A (GB)
Title: Piperidine derivatives and a process for the preparation thereof
IPC: C07D409/12
Filed: 1955-11-24
Abstract: The invention comprises compounds of the general formula <FORM:0773183/IV(b)/1> (wherein R1 represents H, Cl or Br, R2 represents H or Br, R3 represents CH3 and Y represents -CH2- or -C2H4-), and the preparation thereof and of compounds in which Y represents a direct linkage by condensing a compound of the general formula <FORM:0773183/IV(b)/2> with a compound of the general formula <FORM:0773183/IV(b)/3> (wherein Halogen represents chlorine or bromine), preferably at elevated temperature in an inert solvent (e.g. toluene, xylene or chlorobenzene) and in the presence of an alkali metal hydroxide or amide as condensation agent.  The products are useful as antihistaminics and/or sedatives.  In examples: (1) N-(2-thenyl)-m-bromoaniline is heated with 2-(N-methyl-piperidyl - 21) - 1 - chloroethane in xylol in the presence of sodamide to produce N-(2-thenyl)-N - [2 - (N1 - methylpiperidyl - 21) - ethyl - 1] - m-bromoaniline, which converted to its dihydrochloride; (2) N-(5-bromo-2-thenyl)-aniline similarly yields N - (5 - bromo - 2 - thenyl) - N - [2 - (N1 - methylpiperidyl - 21) - ethyl - 1] - aniline (but using sodium hydroxide instead of sodamide); (3) N - (5 - bromo - 2 - thenyl) - m - bromoaniline is reacted as in (2) to give N-(5-bromo - 2 - thenyl) - N - [2 - (N1 - methylpiperidyl - 21) - ethyl - 1] - m - bromoaniline, which is converted to its dihydrochloride; (4) N - (2 - thenyl) - aniline is reacted with N-methyl-4-bromopiperidine as in (1) to produce N - methyl - 4 - amino - N1 - phenyl - N1 - (2 - thenyl)-piperidine, which is converted to its tartrate; (5) N-methyl-3-chloromethylpiperidine similarly yields N-(2-thenyl)-N-(N1-methyl-b -pipecolyl)-aniline, which is converted to its hydrochloride; (6) 2-(N-methylpiperidyl-21)-1-chloroethane similarly gives N-(2-thenyl-N-[2-(N1 - methylpiperidyl - 21) - ethyl - 1] - aniline and its hydrochloride; similarly prepared are: (7) and (8) N-methyl-4-amino-N1-phenyl-N1-(5-chloro- and 5-bromo-2-thenyl)-piperidine and their tartrates; (9) and (10) N-methyl-4-amino-N1 - (m - bromophenyl) - N1 - (5 - bromo - 2 - thenyl)- and -N1-(2-thenyl)-piperidine.  Starting materials. N-(2-Thenyl)-m-bromoaniline is prepared by warming m-bromoaniline with 2-thenyl chloride in aqueous sodium bicarbonate solution. N-(5-Bromo-2-thenyl)-aniline and -m-bromoaniline (the hydrochlorides of which are described) are prepared by similarly condensing 5-bromo-2-thenyl chloride with aniline and m - bromoaniline respectively.  N - Methyl - 4 - bromopiperidine (the hydrobromide of which is described) is prepared by treating N - methyl - 4 - hydroxypiperidine with thionyl bromide.  Specification 717,227 is referred to.ALSO:As antihistamines and/or sedatives may be employed piperidine derivatives of the general formula <FORM:0773183/VI/1> (wherein R1 represents H, Cl or Br, R2 represents H or Br, R3 represents CH3 and Y represents - CH2 -, - C2H4 - or a direct linkage) or their salts.  Thus N - methyl-4 - amino - N1 - phenyl - N1 - (2 - thenyl) - piperidine may be used for combatting allergic diseases by administering it orally, intravenously in combination with a soluble calcium salt, or externally in the form of an ointment. Compounds in which Y is - CH2 - or - C2H4 - may be administered orally or parenterally, e.g. intermuscularly, when simultaneous antihistaminic and sedative action is desired. Specification 717,227 [Group IV(b)] is referred to.