【结 构 式】 |
【药物名称】Amitivir, LY-217896 【化学名称】1,3,4-Thiadiazol-2-ylcyanamide 【CA登记号】111393-84-1, 111393-93-2 (Na salt) 【 分 子 式 】C3H2N4S 【 分 子 量 】126.14019 |
【开发单位】Lilly (Originator) 【药理作用】ANTIINFECTIVE THERAPY, Antiviral Drugs |
合成路线1
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.
【1】 Wheeler, W.J.; Blanchard, W.B.; The synthesis of 1,3,4-thiadiazol-2-ylcyanamide sodium, a potentially useful anti-influenza agent and its [5-14C] and [UL-13C3] isotopomers. J Label Compd Radiopharm 1992, 31, 7, 495. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 12954 | 1-Hydrazinecarbothioamide; Thiosemicarbazide | 79-19-6 | CH5N3S | 详情 | 详情 |
(II) | 14590 | Formic acid | 64-18-6 | CH2O2 | 详情 | 详情 |
(III) | 14591 | 2-Amino-1,3,4-thiadiazole; 1,3,4-Thiadiazol-2-amine; 1,3,4-Thiadiazol-2-ylamine | 4005-51-0 | C2H3N3S | 详情 | 详情 |
(IV) | 14592 | 3-benzyl-1,3,4-thiadiazol-2(3H)-imine | C9H9N3S | 详情 | 详情 | |
(V) | 14593 | N-[3-benzyl-1,3,4-thiadiazol-2(3H)-ylidene]cyanamide | C10H8N4S | 详情 | 详情 |