Laquinimod, SAIK-MS compound, ABR-215062

拉喹莫德Chemical Name: 5-Chloro-N-ethyl-4-hydroxy-1-methyl-2-oxo-N-phenyl-1,2-dihydroquinoline-3-carboxamide
CAS No. 248281-84-7
项目整合开发状态: Phase II
项目研究机构: Active Biotech (Originator), Teva (Licensee)
合成路线:5-Chloroisatoic anhydride (I) is alkylated with iodomethane and NaH to afford (II).Subsequent condensation of anhydride (II) with the malonic monoamide (III) in the presence of NaH in hot DMA furnishes the target quinoline carboxamide.

合成路线:Reaction of 2-amino-6-chlorobenzoic acid (I) with phosgene and NaHCO3 in dioxane gives 5-chloroisatoic anhydride (II),which is methylated by means of iodomethane and NaH in DMF to yield 5-chloro-1-methylisatoic anhydride (III).Finally,anhydride (III) is condensed with the malonic monoamide (IV) by means of NaH in hot dimethylacetamide.Alternatively,condensation of anhydride (III) with ethoxy malonyl chloride (V) by means of NaOMe and triethylamine in dichloromethane affords 5-chloro-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3- carboxylic acid ethyl ester (VI),which is finally condensed with N-ethylaniline (VII) in refluxing toluene.Alternatively,ester (VI) is hydrolyzed by means of concentrated HCl in hot Ac2O to give the carboxylic acid (VIII),which is finally condensed with N-ethylaniline (VII) by means of SOCl2 and TEA in dichloromethane