Amitivir, LY-217896

阿米替韦 氰酰胺,N-1,3,4-噻二唑-2-基-,钠盐(1:1) Chemical Name: 1,3,4-Thiadiazol-2-ylcyanamide; 2-(Cyanamino)-1,3,4-thiadiazole
CAS No. 111393-84-1, 111393-93-2 (Na salt)
项目整合开发状态: Phase I
项目研究机构: Lilly (Originator)
合成路线:The synthesis of LY-217896 and its [5-14C]- and uniformly labeled [UL-13C]-isotopomers has been described:The cyclization of thiosemicarbazide (I) with formic acid (II) at 80-90 C gives 2-amino-1,3,4-thiadiazole (III),which is protected with benzyl chloride in refluxing isopropanol to yield 3-benzyl-1,3,4-thiadiazol-2(3H)-imine (IV).The reaction of (IV) with cyanogen bromide by means of NaHCO3 in methanol - water affords N-(3-benzyl-1,3,4-thiadiazol-2(3H)-ylidene)cyanamide (V),which is finally deprotected with AlCl3 in dichloromethane.The [5-14C]-isotopomer is obtained using [14C]-labeled formic acid in the first step of the synthesis,and the [UL-13C]-isotopomer is obtained using [13C]-labeled thiosemicarbazide (I) and [13C]-formic acid.[13C]-Labeled (I) is synthesized by reaction of potassium cyanide-[13C] with sulfur,yielding potassium thiocyanate-[13C],which is reacted with hydrazine to give [13C]-thiosemicarbazide.