【结 构 式】 |
【分子编号】17589 【品名】Ammonia trichloro platinum(II) complex potassium salt 【CA登记号】 |
【 分 子 式 】H3Cl3KNPt 【 分 子 量 】357.56696 【元素组成】H 0.85% Cl 29.74% K 10.93% N 3.92% Pt 54.56% |
合成路线1
该中间体在本合成路线中的序号:(I)AMD473 is prepared by a modified Dhara synthesis: The procedure is similar to that described for the preparation of the platinum(II) precursor of the other mixed amine platinum drug currently in development, JM216. In the first step, potassium amminetrichloroplatinate (II) is reacted with 2-picoline in the presence of iodide at ambient temperature. The direction of substitution in platinum(II) complexes is controlled by the trans effect of the different ligands. Since in [PtCl3(NH3)] the trans effect for Cl > NH3, one of the trans pair of chloride ligands is initially substituted by iodide. Iodide has a much greater trans effect than chloride or ammine ligands and directs further substitution trans to itself. Binding of 2-picoline results in precipitation of the desired isomer [PtCl(I)(NH3)(2-picoline)]. In the second step, the iodide ligand is removed by reaction with silver ions in water at ambient temperature and treatment of the resulting aqua platinum complexes with chloride yields [PtCl2(NH3)(2-picoline)]. This occurs with retention of stereochemistry at platinum, so yielding the pure cis isomer. This complex may be recrystallized from dilute hydrochloric acid.
【1】 Dhara, S.C.; A rapid method for the synthesis of cis-[Pt(NH3)2Cl2]. Indian J Chem 1970, 8, 193-4. |
【2】 Wyer, S.B.; Vollano, J.F.; Higgins, J.D.; Bossard, G.E.; Giandomenico, C.M.; Murrer, B.A.; Abrams, M.J.; Rheinheimer, M.I.; III. Carboxylation of kinetically inert platinum(IV) hydroxy complexes. An entrée into orally active platinum(IV) antitumor agents. Inorg Chem 1995, 34, 1015-21. |
【3】 Kelland, L. R.; Barnard, C.D.J.; AMD473. Drugs Fut 1998, 23, 10, 1062-1065. |
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) | 17589 | Ammonia trichloro platinum(II) complex potassium salt | H3Cl3KNPt | 详情 | 详情 | |
(II) | 17590 | 2-methylpyridine; 2-picoline | 109-06-8 | C6H7N | 详情 | 详情 |
(III) | 17591 | Ammonia 2-methylpyridine chloro iodo platinum complex | C6H10ClIN2Pt | 详情 | 详情 | |
(IV) | 17592 | Acqua ammoia 2-methylpyridine chloro platinum cationic complex | C6H11ClN2OPt | 详情 | 详情 | |
(V) | 17593 | Diacqua ammonia 2-methylpyridine platinum dicationic complex | C6H12N2O2Pt | 详情 | 详情 |