　 -Drug Synthesis Database

【结构式】

【分子编号】50042

【品名】　

【CA登记号】

【分子式】C₆H₁₄I₂N₂Pt

【分子量】563.07958

【元素组成】C 12.8% H 2.51% I 45.08% N 4.98% Pt 34.65%

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：(VII)

Treatment of hexachlorocyclotriphosphazene (I) with L-glutamic acid diethyl ester (II) in toluene in the presence of Et3N provides the ethyl glutamate derivative of cyclotriphosphazene (III), which is then subjected to saponification with LiOH in H2O to furnish compound (IV) (alternatively, the same procedure can be followed by performing the reaction between (I) and L-glutamic acid dimethyl ester (V) to afford the methyl glutamate derivative of cyclotriphosphazene (VI), which is saponified under the same conditions as (III)). Finally, the target product is obtained by reaction of intermediate (IV) with platinum derivative (VII) by means of Ag2SO4 in water, followed by treatment with BaCl2.H2O and precipitation in acetone.

参考文献中间体

合成目标

【1】 Cho, Y.; Sohn, Y.S.; Baek, H.; Lee, C.O.; Synthesis and antitumor activity of cyclotriphosphazene - (diamine)platinum (II) conjugates. Anti-Cancer Drugs 2000, 11, 9, 715.
【2】 Lee, C.O.; Sohn, Y.S.; Baek, H.G. (Il-Yang Pharmaceutical Co., Ltd.; Korea Institute of Science and Technology); Platinum complex conjugated to cyclotriphosphazene, its preparation, and anticancer agent comprising the same. EP 1082331; US 6221906; WO 0058321 .

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)	50037	Phosphonitrilic Chloride; 1,3,5-Triaza-2,4,6-triphosphorin-2,2,4,4,6,6-hexachloride; Hexachlorotriphosphazene; Phosphonitrilic chloride trimer; 1,3,5,2,4,6-Triazatriphosphorine-2,2,4,4,6,6-hexachloride; Hexachlorocyclotriphosphazene	940-71-6	Cl₆N₃P₃	详情	详情
(II)	11013	diethyl (2S)-2-aminopentanedioate		C₉H₁₇NO₄	详情	详情
(III)	50038	diethyl (2S)-2-[(2,4,4,6,6-pentakis[[(1S)-4-ethoxy-1-(ethoxycarbonyl)-4-oxobutyl]amino]-1,3,5,2lambda(5),4lambda(5),6lambda(5)-triazatriphosphinin-2-yl)amino]pentanedioate		C₅₄H₉₆N₉O₂₄P₃	详情	详情
(IV)	50039	dodecalithium (2S)-2-[(2,4,4,6,6-pentakis[[(1S)-1-carboxylato-4-oxido-4-oxobutyl]amino]-1,3,5,2lambda(5),4lambda(5),6lambda(5)-triazatriphosphinin-2-yl)amino]pentanedioate		C₃₀H₃₆Li₁₂N₉O₂₄P₃	详情	详情
(V)	50040	dimethyl (2S)-2-aminopentanedioate		C₇H₁₃NO₄	详情	详情
(VI)	50041	dimethyl (2S)-2-[(2,4,4,6,6-pentakis[[(1S)-4-methoxy-1-(methoxycarbonyl)-4-oxobutyl]amino]-1,3,5,2lambda(5),4lambda(5),6lambda(5)-triazatriphosphinin-2-yl)amino]pentanedioate		C₄₂H₇₂N₉O₂₄P₃	详情	详情
(VII)	50042			C₆H₁₄I₂N₂Pt	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

The platinum nitrate derivative (X) was prepared by two related procedures. Halogen-exchange of potassium tetrachloroplatinate (V) with KI produced the tetraiodoplatinate (VI), which was subsequently reacted with trans-1,2-diaminocyclohexane (VII) to give the diamino chelate (VIII). Alternatively, diamine (VII) was reacted with tetrachloroplatinate (V), yielding chelate (IX). Treatment of either iodo compound (VIII) or its analogous chloride (IX) with silver nitrate furnished the dinitrate compound (X). Finally, the diacid formed by basic hydrolysis of anhydride (IV) was in situ complexed with the platinum compound (X) to generate the title platinum complex.

参考文献中间体

合成目标

【1】 Lin, G.; To, K.K.W.; Wang, X.; Han, X.; Au-Yeung, S.C.F.; Ho, Y.-P.; Potential new antitumor agents from an innovative combination of demethylcantharidin, a modified traditional Chinese medicine, with a platinum moiety. J Med Chem 2001, 44, 13, 2065.
【2】 Ho, Y.P.; Au-Yeung, S.C.F.; Jiang, T.; Han, X.; Wang, X.; Lin, G.; Lu, S. (Chinese University of Hong Kong); Synthesis of platinum complexes and uses thereof. WO 9849174 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	49888	4,10-Dioxatricyclo[5.2.1.0(2,6)]decane-3,5-dione		C₈H₈O₄	详情	详情
(V)	51693	dipotassium tetrachloroplatinate(2-);potassium tetrachloroplatinate(II);potassium tetrachloroplatinate	10025-99-7	Cl₄K₂Pt	详情	详情
(VI)	51694	dipotassium tetraiodoplatinate(2-);potassium tetraiodoplatinate(II);Potassium tetraiodoplatinate	14708-56-6	I₄K₂Pt	详情	详情
(VII)	11130	(1R,2R)-1,2-cyclohexanediamine; (1R,2R)-2-aminocyclohexylamine; cis-1,2-Diaminocyclohexane	20439-47-8	C₆H₁₄N₂	详情	详情
(VIII)	50042			C₆H₁₄I₂N₂Pt	详情	详情
(IX)	23063	(R,R)-Cyclohexane-1,2-diamine dichloro platinum complex		C₆H₁₄Cl₂N₂Pt	详情	详情
(X)	19480	(R,R)-Cyclohexane-1,2-diamine dinitrato platinum complex	n/a	C₆H₁₄N₄O₆Pt	详情	详情

Extended Information