Clofilium phosphate, LY-150378

磷酸氯非铵Chemical Name: [4-(p-Chlorophenyl)butyl]diethylheptylammonium phosphate (1:1); N,N-Diethyl-N-heptyl-4-(p-chlorophenyl)butylammonium phosphate (1:1); 4-Chloro-N,N-diethyl-N-heptylbenzenebutanaminium phosphate (1:1)
CAS No. 68379-03-3
项目整合开发状态: Biological Testing
项目研究机构: Lilly (Originator)
合成路线:The reaction of p-chlorobenzaldehyde (I) sodium cyanide and ethyl acetate gives ethyl 4-(p-chlorophenyl)-4-oxobutyrate (II),which is hydrolyzed with KOH to the corresponding free acid (III).The reduction of (III) with Zn and aqueous HCl affords 4-(p-chlorophenyl)butyric acid (IV),which is condensed with heptylamine (B) by means of oxalyl chloride (A) in refluxing benzene to yield N-heptyl-4-(p-chlorophenyl)butyramide (V),which is reduced with diborane in refluxing THF to afford N-heptyl-4-(p-chlorophenyl)butylamine (VI).The acetylation of (VI) with acetyl chloride (C) by means of Na2CO3 in acetone gives N-acetyl-N-heptyl-4-(p-chlorophenyl)butylamine (VII),which is reduced with diborane as before to yield N-ethyl-N-heptyl-4-(p-chlorophenyl)butylamine (VIII).The quaternization of (VIII) with refluxing ethyl bromide (D) gives N,N-diethyl-N-heptyl-4-(p-chlorophenyl)butylammonium bromide (IX),which by elution through a column with Dowex 1-X8,hydroxide form,resin is converted into N,N-diethyl-N-heptyl-4-(p-chlorophenyl)butyl ammonium hydroxide (X).Finally,this compound is salified with diluted aqueous phosphoric acid.