Patent GB-1345872-A (GB)
Title: Amino-and acylamino-pyridine and hydropyridine derivatives
IPC: C07D333/56
Filed: 1970-09-03
Abstract: 1345872 Amino- and acylamino-pyridines and -hydropyridines JOHN WYETH & BRO Ltd 24 Aug 1971 [3 Sept 1970 22 July 1971] 42090/70 and 34376/71 Heading C2C [Also in Division A5] The invention comprises compounds of Formula I in which the ring system of Formula II represents a ring system of the general Formula IIa, II or IIc W represents a cycloalkyl radical containing five to seven ring carbon atoms or an aryl or heteroaryl radical other than an indolyl radical, all of which radicals may be substituted or unsubstituted; A represents a lower alkylene radical, a mono- or di-keto lower-alkylene radical or an oxime, aminoguanidone or substituted or unsubstituted hydrazone derivative thereof, a hydroxy-lower-alkylene radical, or a bivalent radical of the formula -NH-CO-(CH 2 ) n -, or -O-(lower-alkylene)-; R<SP>1</SP> represents hydrogen, halogen or lower alkyl; n is the integer 1, 2 or 3; Acyl is an acyl radical; X<SP>(-)</SP> is an anion; R<SP>2</SP> is hydrogen or the group -COR when the ring system of Formula II represents a ring system of Formula II(a) or II(c) and the group -COR when the ring system of Formula II represents a ring system of Formula II(b) wherein R represents a substituted or unsubstituted aryl radical (including heteroaryl radicals), aryloxy, aryl-lower-alkyl, aryl-loweralkyloxy, diaryl-lower-alkyl, cycloalkyl containing five to seven ring carbon atoms, lower alkoxy or lower alkyl; and the term "lower" means that the radical contains from 1 to 6 carbon atoms; and the acid addition and quaternary ammonium salts of those compounds wherein the ring system of Formula II represents a ring system of Formula (IIb) or (II(c); with the provisos that (i) when W is unsubstituted phenyl, and A is lower alkylene, and R<SP>1</SP> is lower alkyl, and R<SP>2</SP> is -COR wherein R is unsubstituted or substituted phenyl then the ring system of Formula II is a ring system of Formula II(a) or II(c) and (ii) when W is unsubstituted phenyl, and A is methylene or ethylene, and R<SP>1</SP> is hydrogen, and R<SP>2</SP> is hydrogen or the group -COR wherein R is phenyl, which may be substituted or unsubstituted, phenyllower-alkyl, or lower alkyl, then the ring system of Formula II is a ring system of Formula II(a) or (IIb); (iii) when W is a substituted or unsubstituted 5 or 6 membered heteroaryl radical, and A is a or -CH 2 CH 2 - radical, and R<SP>1</SP> is hydrogen or lower alkyl, the R<SP>2</SP> is the group -COR wherein R is other than lower alkyl; (iv) when W is a phenyl or a 5 or 6 membered heteroaryl radical, both of which may be substituted or unsubstituted, and A is a radical, and R<SP>1</SP> is hydrogen, and the ring system of Formula II is a ring system of Formula II(a), then R<SP>2</SP> is the group -COR wherein R is other than lower alkyl; and (v) when W is substituted or unsubstituted phenyl and A is a radical, and R<SP>1</SP> is hydrogen or lower alkyl, then R<SP>2</SP> is the group -COR wherein R is other than lower alkyl, and the preparation thereof by standard methods, e.g. alkylation, acylation, hydrolysis, reduction and interconversion of substituents. 2 - (4 - Benzamidopiperidino) ethyl hydroxymethyl ketone is prepared by reacting 4-benzamidopiperidine with hydroxymethyl vinyl ketone. 3 - (2 - Tosyloxyethyl)bemo[b]thiophene is prepared by reacting 3-(2-hydroxyethyl)benzo- [b]thiophene with p-toluenesulphonyl chloride. 2 - (2 - Tosyloxyethyl) - 5 - phenylthiophene is similarly prepared. N - propargyl - 2,6 - dichloropropionanilide is prepared by reacting 2,6-dichloroaniline with propionyl chloride and reacting the resulting 2,6-dichloropropionanilide with propargyl bromide. 1 - (4,4 - Diethoxybutyl) - 4 - benzamidopiperidine is prepared by reacting 4-benzamidopiperidine with paraformaldehyde followed by propiolaldehyde diethylacetal to give 4-benzamido - 1 - (4,4 - diethoxybut - 2 - ynyl)piperidine and hydrogenating this in the presence of palladium-on-carbon. 2 - (2 - Hydroxyethyl) - 5 - phenylthiophene is prepared by reacting 2-phenylthiophene with butyllithium and then with ethylene oxide. 1 - (2 - Ethoxycarbonylethyl)- 4 - benzamidopiperidine is prepared by reacting 4-benzamidopiperidine with ethyl 3-bromopropionate. 1-Phenethyl-4-aminopiperidine is prepared by hydrolysing 1-phenethyl-4-acetamidopiperidine.