Patent GB-729003-A (GB)
Title: Diphenyl-acetyl diamines and salts thereof and the manufacture of same
IPC: C07C233/12
Filed: 1953-06-10
Abstract: The invention comprises compounds of the formula <FORM:0729003/IV (b)/1> wherein the alkyl groups each contain from one to four carbon atoms and need not be identical, and salts thereof (including acid addition salts and quaternary ammonium salts).  Such compounds are prepared by the action of diphenyl acetyl chloride on the appropriate 1-alkylamino-1 - phenyl - 2 - dialkylamino - ethanes or - propanes, treatment of the product with an alkaline agent, and, if desired, treating the base so formed with the appropriate acid or quaternizing agent.  In examples (1) styrene oxide and isopropylamine are reacted to give 1-hydroxy-1-phenyl - 2 - isopropylamino - ethane which is reacted with formaldehyde and formic acid to give 1 - hydroxy - 1 - phenyl - 2 - (methyl - isopropylamino)-ethane.  The latter compound is reacted with thionyl chloride to give 1-chloro-1-phenyl - 2 - (methyl - isopropyl - amino) - ethane hydrochloride; this compound reacted in methanol with methylamine yields 1-methylamino - 1 - phenyl - 2 - (methyl - isopropylamino)-ethane dihydrobromide which is heated with diphenyl-acetyl chloride to give, on making the product alkaline, and treating the product in ether with hydrogen bromide, 1-(diphenyl-acetyl - methylamino) - 1 - phenyl - 2 - (methyl-isopropyl - amino) - ethane hydrobromide; (2) by reacting 1 - chloro - 1 - phenyl - 2 - (methyl-iso - propyl - amino) - ethane (prepared as in (1)) with ethylamine in place of methylamine, and then proceeding as in example (1), 1-(diphenylacetyl - ethyl - amino) - 1 - phenyl - 2 - (methyl - isopropylamino) - ethane hydrobromide is obtained; (3) similarly to (2) is prepared 1 - isopropylamino - 1 - phenyl - 2-(methyl - isopropylamino) - ethane dihydrobromide which is reacted with diphenylacetyl chloride, to give, on making the product alkaline and treating with hydrogen bromide, 1-(diphenylacetyl - isopropylamino) - 1 - phenyl - 2-(methylisopropyl - amino) - ethane hydrobromide; (4) styrene oxide and methyl n-butyl amine are reacted to give 1-hydroxy-1-phenyl-2-(n - butyl - methylamino) - ethane which is heated with thionyl chloride and the corresponding 1-chloro-compound obtained is reacted with methylamine giving 1-methylamino-1-phenyl-2 - (n - butyl - methyl - amino) - ethane. The latter compound is reacted with diphenyl-acetyl chloride to give 1 - (diphenylacetyl - methylamino) - 1 - phenyl - 2 - (n - butyl - methylamino)-ethane, which is converted to its hydrobromide and methobromide; (5) 1-methylamino - 1 - phenyl - 2 - dimethylamino - propane and diphenyl-acetyl chloride are reacted to give 1 - (diphenylacetyl - methyl - amino) - 1 - phenyl-2 - dimethylamino - propane; (6) 1 - chloro - 1-phenyl - 2 - dimethylamino propane (produced from N-methyl-ephedrine and thionyl chloride) is reacted with isopropylamine to give 1-isopropylamino - 1 - phenyl - 2 - dimethylamino - propane hydrochloride, reaction of which with diphenyl-acetyl chloride yields 1-(diphenylacetyl-isopropyl - amino) - 1 - phenyl - 2 - dimethylamino - propane hydrobromide; (7) isopropylamine and 1 - chloro - 1 - phenyl - 2 - dimethylamino - ethane hydrochloride are reacted to give 1 - isopropylamino - 1 - phenyl - 2 - dimethyl - amino - ethane dihydrochloride, reaction of which with diphenyl-acetyl chloride gives 1 - (diphenyl - acetyl - 1 - isopropylamino)-1 - phenyl - 2 - dimethylamino - ethane hydrochloride; (8) 1 - chloro - 1 - phenyl - 2 - (ethylmethyl - amino) - propane - hydrochloride (from N-ethyl-ephedrine and thionyl chloride) is reacted with isopropylamine to give 1-isopropylamino - 1 - phenyl - 2 - (ethyl - methyl - amino)-propane, reaction of which with diphenyl-acetyl chloride gives 1 - (diphenyl - acetyl - isopropylamino) - 1 - phenyl - 2 - (ethyl - methyl - amino)-propane; (9) 1 - chloro - 1 - phenyl - 2 - (ethyl-methyl - amino) - propane hydrochloride (prepared as in example 8) is reacted with methylamine to give 1 - methyl - amino - 1 - phenyl-2 - (ethyl - methyl - amino) - propane.  The latter compound is reacted with diphenylacetyl chloride to give 1-(diphenylacetylmethyl - amino) - 1 - phenyl - 2 - (ethyl - methylamino) - propane hydrobromide; (10) 1-chloro - 1 - phenyl - 2 - (methyl - isopropylamino) - propane hydrochloride (from N - isopropyl-ephedrine and thionyl chloride) and isopropylamine are reacted to give 1-isopropylamino - 1 - phenyl - 2 - (methyl - isopropylamino) - propane dihydrobromide, which on reaction with diphenylacetyl chloride gives 1-(diphenylacetyl - isopropyl - amino) - 1 - phenyl-1 - (methyl - isopropyl - amino - propane.