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【结 构 式】 
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【分子编号】61657 【品名】dichloroplatinum 【CA登记号】 |
【 分 子 式 】Cl2Pt 【 分 子 量 】265.9854 【元素组成】Cl 26.66% Pt 73.34% |
合成路线1
该中间体在本合成路线中的序号：(VII)Enloplatin can be obtained by two related ways: 1) The cyclization of 2,2'-dichloroethylether (I) with malonodinitrile (II) by means of K2CO3 in refluxing acetonitrile gives tetrahydropyran-4,4-dicarbonitrile (III), which is reduced with BH3 in THF yielding tetrahydropyran-4,4-dimethamine (IV). The reaction of (IV) with potassium tetrachloroplatinate (V) affords dichloro(tetrahydropyran-4,4-dimethanamine-N,N')platinum(II) (VI), which is finally condensed with cyclobutane-1,1-dicarboxylic acid silver salt (VIII) in water. 2) The reaction of potassium tetrachloroplatinate (V) with DMSO gives dichloro-bis(dimethylsulfoxide)platinum(II) (VII), which is condensed with silver salt (VIII) to afford (1,1-cyclobutane-dicarboxylato-O,O')bis(dimethylsulfoxide)platinum(II) (IX), which is finally treated with diamine (IV) as before.
| 【1】 Child, R.G.; Bitha, P.; Hlavka, J.J.; Lin, Y. (American Cyanamid Co.); (Gem-heterocyclodimethanamine-N,N')platinum complexes. EP 0232784; US 4880790 . |
| 【2】 Bitha, P.; Hlavka, J.J.; Lin, Y. (American Cyanamid Co.); Synthesis of cisplatinum analogs. EP 0296321 . |
| 【3】 Carvajal, S.G.; Citarella, R.V.; Bitha, P.; et al.; Water-soluble third generation antitumor Pt complexes, [2,2-bis(aminomethyl)-1,3-propanediol-N,N']- [1,1-cyclobutanedicarboxylato(2-)-O,O']Pt(II) and [1,1-cyclobutanedicarboxylato(2-)-O,O']-[tetrahydro-4H-pyran-4,4-dimethanamine-N,N']Pt(II). J Med Chem 1989, 32, 8, 2015. |
| 【4】 Castaner, J.; Prous, J.; Enloplatin. Drugs Fut 1992, 17, 6, 459. |
| 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) | 12060 | Bis(2-chloroethyl) ether; 1-Chloro-2-(2-chloroethoxy)ethane; 2,2'-Dichlorodiethyl ether | 111-44-4 | C4H8Cl2O | 详情 | 详情 |
| (II) | 12061 | Malononitrile | 109-77-3 | C3H2N2 | 详情 | 详情 |
| (III) | 12062 | Tetrahydro-4H-pyran-4,4-dicarbonitrile | C7H8N2O | 详情 | 详情 | |
| (IV) | 12063 | [4-(Aminomethyl)tetrahydro-2H-pyran-4-yl]methanamine; [4-(Aminomethyl)tetrahydro-2H-pyran-4-yl]methylamine | C7H16N2O | 详情 | 详情 | |
| (V) | 51693 | dipotassium tetrachloroplatinate(2-);potassium tetrachloroplatinate(II);potassium tetrachloroplatinate | 10025-99-7 | Cl4K2Pt | 详情 | 详情 |
| (VI) | 12064 | 4,4-Bis(aminomethyl)tetrahydropyran dichloro platinum complex | C7H16Cl2N2OPt | 详情 | 详情 | |
| (VII) | 61657 | dichloroplatinum | Cl2Pt | 详情 | 详情 | |
| (VIII) | 12065 | Bis(dimethylsulfoxide-S,S')dichloroplatinum | C6H6Ag2O4 | 详情 | 详情 | |
| (IX) | 12066 | Cyclobutane-1,1-dicarboxylic acid platinum salt | C6H6O4Pt | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)Zeniplatin can be obtained by two related ways: 1) The reaction of dimethylsulfoxide with potassium tetrachloroplatinate (I) gives bis(dimethylsulfoxide-S,S')dichloroplatinum (II), which is then condensed with silver cyclobutane-1,1-dicarboxylate (III) in water to yield bis(dimethylsulfoxide-S,S')(1,1-cyclobutanedicarboxylato-O,O')platinum (IV). Finally, this compound is treated with 2,2-bis(aminomethyl)-1,3-propanediol (V) in refluxing water. 2) The reaction of potassium tetrachloroplatinate (I) with diamine (V) in water gives [2,2-bis(aminomethyl)-1,3-propanediol-N,N']dichloroplatinum (IV), which is treated with the silver salt (III) as before. The diamine (V) is prepared by reaction of 2,2-bis(bromomethyl)-1,3-propanediol (VII) with sodium azide in hot DMF to give 2,2-bis(azidomethyl)-1,3-propanediol (VIII), which is then reduced with hydrogen over Pt.
| 【1】 Grassing Child, R.; Bitha, P.; Hlavka, J.J.; Lin, Y. (Zyma); [2,2-Bis(aminomethyl)-1,3-propanediol-N,N']platinum complexes. AU 8432572; EP 0140830; ES 8802308; GB 2145720; JP 1985149581; US 4665202 . |
| 【2】 Bitha, P.; Hlavka, J.J.; Lin, Y. (American Cyanamid Co.); Synthesis of cisplatinum analogs. EP 0296321 . |
| 【3】 Carvajal, S.G.; Citarella, R.V.; Bitha, P.; et al.; Water-soluble third generation antitumor Pt complexes, [2,2-bis(aminomethyl)-1,3-propanediol-N,N']- [1,1-cyclobutanedicarboxylato(2-)-O,O']Pt(II) and [1,1-cyclobutanedicarboxylato(2-)-O,O']-[tetrahydro-4H-pyran-4,4-dimethanamine-N,N']Pt(II). J Med Chem 1989, 32, 8, 2015. |
| 【4】 Prous, J.; Castaner, J.; Zeniplatin. Drugs Fut 1992, 17, 6, 471. |
| 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) | 51693 | dipotassium tetrachloroplatinate(2-);potassium tetrachloroplatinate(II);potassium tetrachloroplatinate | 10025-99-7 | Cl4K2Pt | 详情 | 详情 |
| (II) | 61657 | dichloroplatinum | Cl2Pt | 详情 | 详情 | |
| (III) | 12065 | Bis(dimethylsulfoxide-S,S')dichloroplatinum | C6H6Ag2O4 | 详情 | 详情 | |
| (IV) | 12069 | Cyclobutane-1,1-dicarboxylic acid platinum salt | C6H6O4Pt | 详情 | 详情 | |
| (V) | 12070 | 2,2-Bis(aminomethyl)-1,3-propanediol | C5H14N2O2 | 详情 | 详情 | |
| (VI) | 12071 | 2,2-Bis(hydroxymethyl)propane-1,3-diamine dichloro platinum complex | C5H14Cl2N2O2Pt | 详情 | 详情 | |
| (VII) | 12072 | Dibromoneopentyl glycol; 2,2-Bis(bromomethyl)-1,3-propanediol | 3296-90-0 | C5H10Br2O2 | 详情 | 详情 |
| (VIII) | 12073 | 2,2-Bis(azidomethyl)-1,3-propanediol | C5H10N6O2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(V)The known N-(2-hydroxypropyl)-methacrylamide copolymer (I) which has a p-nitrophenyl peptide side chain is coupled to ethyl aminomalonate (II) in the presence of Et3N in DMF to give the corresponding amide (III). Alkaline hydrolysis of the diethyl malonate ester groups of (III) affords the sodium carboxylate salt (IV). This is then complexed with the platinum species, generated in situ from cisplatin (V) and silver nitrate, to produce the title polymer-linked platinum complex.
| 【1】 Duncan, R.; Evagorou, E.G.; Buckley, R.G.; Gianasi, E. (Access Pharmaceuticals, Inc.); Polymer-platinum cpds.. WO 9847537 . |