Bis(dimethylsulfoxide-S,S')dichloroplatinum -Drug Synthesis Database

【结构式】

【分子编号】12065

【品名】Bis(dimethylsulfoxide-S,S')dichloroplatinum

【CA登记号】

【分子式】C₆H₆Ag₂O₄

【分子量】357.84764

【元素组成】C 20.14% H 1.69% Ag 60.29% O 17.88%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VIII)

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.

参考文献中间体

合成目标

【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：(III)

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.

参考文献中间体

合成目标

【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

Extended Information