Patent GB-404674-A (GB)
Title: Manufacture of therapeutically active compounds
IPC: C07D231/06
Filed: 1932-07-19
Abstract: Therapeutically-valuable compounds are prepared by combining the nitrogen atom of an amine of the formula NHRR (where RR represents two identical or different monovalent hydroaromatic hydrocarbon residues which may be bound to one another by a methylene group, or two identical or different hydroaromatic-aliphatic hydrocarbon residues) by means of an aliphatic residue with a nitrogen atom of a pyridine or quinoline compound containing a tautomeric amino group. Suitable amines of the above formula are dicyclohexylamine, perhydroacridine, dihexahydrobenzylamine, dicyclohexylethyl-amine and cyclohexyl-hexahydrobenzylamine (obtainable by interaction of hexahydrobenzylamine with cyclohexyl bromide).  According to the examples, (1) dicyclohexylamine is treated with ethylene chlorhydrin, the resulting b -dicyclohexylaminoethanol converted by means of thionyl chloride into b -dicyclohexylaminoethyl chloride, and the latter then combined with 2-aminopyridine, 2-aminoquinoline or the sodium compound of 2-aminopyridine to give 1-dicyclohexylaminoethylpyridone - 2 - imide, 1 - dicyclohexylaminoethylquinolone - 2 - imide or 2 - dicyclohexylaminoethylaminopyridine respectively; (2) 1 - dihexahydrobenzylaminoethylpyridone-2-imide is prepared by treating dihexahydrobenzylamine (obtained by reducing hexahydrobenzonitrile) with ethylene chlorhydrin, converting the b -dihexahydrobenzylaminoethanol with thionyl chloride into its ethyl chloride and combining the latter with 2-aminopyridine; (3) perhydroacridine, prepared by hydrogenating acridine in a solvent with a nickel catalyst, is similarly treated first with ethylene chlorhydrin and then with thionyl chloride, and the resulting chlorethylperhydroacridine combined either with 2-aminopyridine, forming 1-perhydroacridylethylpyridone-2-imide, or with 6-ethoxy-4-aminoquinaldine to give 1-perhydroacridylethyl - 2 - methyl - 6 - ethoxyquinolone - 4 - imide; (4) 1-(1<1>-dicyclohexylaminopentyl-4<1>-)-pyridone-2-imide is obtained by interaction of 2 - aminopyridine with 1 - dicyclohexylaminopentylchloride-4, obtained from 1-dicyclohexylaminopentanol-4 and thionyl chloride; 1-dicyclohexylaminopentanol-4 is obtained by heating b -dicyclohexylaminoethyl chloride first with acetic acid ester and then with acetic acid, and reducing the resulting ketone with hydrogen in the presence of nickel; (5) di-p-methylcyclohexylaminoethyl chloride, prepared from p-methylcyclohexyl bromide by treatment with aminoethanol and then with thionyl chloride, is reacted with 2-aminopyridine to give di-p-methylcyclohexylaminoethylpyridone - 2 - imide; (6) 1 - dicyclohexylaminoethyl - 5 - oxypyridone-2-imide and the corresponding 5-ethoxy compound are prepared by reacting b -dicyclohexylaminoethyl chloride with 2-amino-5-oxypyridine (see Specification 360,188) and 2-amino-5-ethoxypyridine respectively. The following is a description of the preparation of the samples furnished:--(1) cyclohexylaminoethanol is heated with p-methylcyclohexylbromide, the product converted with thionyl chloride into cyclohexyl - p - methylcyclohexylaminoethyl chloride, and the latter then combined with 2-aminopyridine to form 1-cyclohexyl-p-methylcyclohexylaminoethylpyridone - 2 - imide; (2) phenylethylamine is treated with benzyl chloride, the resulting benzylphenylethylamine then hydrogenated using a nickel catalyst to give hexahydrobenzylhexahydrophenylethylamine, which is caused to react first with ethylene chlorhydrin and then with thionyl chloride; by interaction of the resulting ethyl chloride compound with 2-aminopyridine, 1-hexahydrobenzyl - hexahydrophenylethylaminoethylpyridone-2-imide is obtained. The formulae of the products are stated.