Lortalamine, LM-1404

氯他拉明Chemical Name: (?-(4aR*,10R*,10aS*)-8-Chloro-1,2,3,4,10,10a-hexahydro-2-methyl-4a,10-(iminoethano)-4aH-[1]benzopyrano[3,2-c]pyridin-12-one; (?-(4aR*,10R*,10aS*)-4a-Amino-8-chloro-2-methyl-1,2,3,4,4a,10a-hexahydro-10H-benzopyrano[3,2-c]pyridin-10-ylacetic acid lactam
CAS No. 70384-91-7, 76612-20-9 ((4aR,10R,10aR)isomer)
项目整合开发状态: Preclinical
项目研究机构: Lipha (Originator)
合成路线:This compound can be obtained by two related ways:1) By cyclization of ethyl 6-chlorocoumarin-3-carboxylate (I) and N-methyl-4-piperiodone (II) by means of sodium acetate in refluxing ethanol,followed by a treatment with refluxing concentrated hydrochloric acid.2) The cyclization of (I) and (II) by means of ammonium acetate in refluxing ethanol,followed by a treatment with cool concentrated hydrochloric acid gives the lactam od the ethyl monoester of 4a-amino-8-chloro-2-methyl-1,2,3,4,4a,10a-hexahydro(10H)-benzopyrano[3,2-c]pyrid-10-ylmalonic acid (III),which is hydrolyzed with KOH in refluxing ethanol-water to give the corresponding free acid (IV).Finally,this compound is decarboxylated by a treatment with NaHCO3 in refluxing water.

合成路线:The Grignard condensation of 2,3-dichloroiodobenzene (I) with CO2 by means of Mg / ether gives 2,3-dichlorobenzoic acid (II),which is converted to the corresponding acyl chloride (III) by refluxing with SOCl2.The reaction of (III) with cuprous cyanide and KI in refluxing xylene yields 2,3-dichlorobenzoyl cyanide (IV).Finally,this compound is cyclized with aminoguanidine (V) in DMSO.