新产品编号:1449621

Chemical Name: 3-[2-Amino-3-(isopropylsulfanyl)imidazo[1,2-a]pyridin-6-yl]-N-methyl-3-phenyl-2(E)-propenamide
项目整合开发状态: Biological Testing
项目研究机构: Lilly (Originator)
合成路线:Friedel-Crafts acylation of benzene with 6-chloronicotinyl chloride (I) using AlCl3 afforded ketone (II).Subsequent displacement of the chlorine atom of (II) by means of ethanolic ammonia at 145 C in a pressure reactor led to the aminopyridine (III),which was converted to sulfonamide (IV) by means of tosyl chloride in pyridine.Alkylation of the pyridine N of (IV) with iodoacetamide gave (V),and further cyclization in the presence of trifluoroacetic anhydride produced the imidazopyridine (VI).Phosphonate (VIII) was prepared by treatment of triethyl phosphonoacetate (VII) with methylamine.Horner-Emmons condensation of this phosphonate with ketone (VI) yielded the E-propenamide (IX).Selective iodination of (IX) at position 3 using N-iodosuccinimide furnished iodide (X).This compound was first deprotonated with PhLi,then subjected to a halogen-metal exchange reaction with tert-butyllithium,and the resulting trianion was reacted with isopropyl isopropanethiolsulfonate to give sulfide (XI).Finally,smooth hydrolysis of the trifluoroacetamide group of (XI) employing MeOH-CH2Cl2 in the presence of silica gel provided the title compound.