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【结 构 式】 
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【分子编号】11130 【品名】(1R,2R)-1,2-cyclohexanediamine; (1R,2R)-2-aminocyclohexylamine; cis-1,2-Diaminocyclohexane 【CA登记号】20439-47-8 |
【 分 子 式 】C6H14N2 【 分 子 量 】114.19064 【元素组成】C 63.11% H 12.36% N 24.53% |
合成路线1
该中间体在本合成路线中的序号：(II)A new synthesis of [195mPt]-tetraplatin has been described: By reaction of potassium hexachloroplatinate (195Pt) with trans-1,2-cyclohexanediamine in water.
合成路线2
该中间体在本合成路线中的序号：(II)Potassium tetrachloroplatinate (I) is treated with an equivalent amount of 1,2-diaminocyclohexane in degassed water under nitrogen. The precipitated complex (II) is filtered and washed with HCl, ethanol and diethyl ether. The precipitate is dissolved in N,N-dimethylformamide, filtered and reprecipitated by addition of methanol. The precipitate is collected and suspended in 0.5N HCl and treated with chlorine gas at 100 C to convert to the tetrachloroplatinum(IV) complex. Removal of excess chlorine and then solvent, dissolution in methanol, filtration and removal of the methanol by vacuum yields the yellow product (III) in about 83% yield.
| 【1】 HAugwitz, R.D.; Wolpert-DeFilippes, M.K.; Anderson, W.K.; NArayanan, V.L.; Quagliato, D.A.; Synthesis, physical properties, and antitumor activity of tetraplatin and related tetrachloroplatinum(IV) stereoisomers of 1,2-diaminocyclohexane. Cancer Treat Rep 1986, 70, 8, 997-1002. |
合成路线3
该中间体在本合成路线中的序号：(I)Dichlorocyclohexane-1,2-diamine platinum complex (II) was prepared from (R,R)-1,2-cyclohexanediamine (I) according to a known method. Subsequent treatment of (II) with aqueous silver nitrate produced the diaqua complex (III). Finally, displacement of H2O by means of sodium myristate (IV) gave rise to the title compound.
| 【1】 Maeda, M.; Sasaki, T. (Sumitomo Pharmaceuticals Co., Ltd.); Liposoluble platinum (II) complex and preparation thereof. AU 8654358; EP 0193936; JP 1987000096 . |
| 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) | 11130 | (1R,2R)-1,2-cyclohexanediamine; (1R,2R)-2-aminocyclohexylamine; cis-1,2-Diaminocyclohexane | 20439-47-8 | C6H14N2 | 详情 | 详情 |
| (II) | 23063 | (R,R)-Cyclohexane-1,2-diamine dichloro platinum complex | C6H14Cl2N2Pt | 详情 | 详情 | |
| (III) | 40706 | C6H14Cl2N4O6Pt | 详情 | 详情 | ||
| (IV) | 40707 | sodium myristate | 822-12-8 | C14H27NaO2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(I)Treatment of (R,R)-1,2-diaminocyclohexane (I) with triphenylmethyl chloride produced the N-trityl derivative (II). Subsequent condensation of (II) with glyoxal (III) gave the bis-imine (IV), which was reduced to amine (V) using LiBH4. Cleavage of the N-trityl groups of (V) with HCl in acetone afforded tetraamine (VI). This was then condensed with 2,6-diacetylpyridine (VII) in the presence of MnCl2 to furnish the cyclic bis-imine manganese complex (VIII). Finally, transfer hydrogenation of the imine functions of (VIII) using ammonium formate and Pd/C produced the cyclic pentaamino derivative as a diastereomeric mixture. The title isomer was then purified by separative partition between H2O and CH2Cl2.
| 【1】 Udipi, K.; Joardar, S.; Forster, D.; Riley, D.; Henke, S.; Brethaur, K.; Thurmond, B.; Ornberg, R. (Pharmacia Corp.); Biomaterials modified with superoxide dismutase mimics. WO 0072893 . |
| 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) | 11130 | (1R,2R)-1,2-cyclohexanediamine; (1R,2R)-2-aminocyclohexylamine; cis-1,2-Diaminocyclohexane | 20439-47-8 | C6H14N2 | 详情 | 详情 |
| (II) | 48511 | N-[(1R,2R)-2-aminocyclohexyl]-N-tritylamine; (1R,2R)-N(1)-trityl-1,2-cyclohexanediamine | C25H28N2 | 详情 | 详情 | |
| (III) | 32557 | glyoxal; 2-oxoacetaldehyde | 107-22-2 | C2H2O2 | 详情 | 详情 |
| (IV) | 48512 | (1R,2R)-N(1)-trityl-N(2)-((E)-2-[[(1R,2R)-2-(tritylamino)cyclohexyl]imino]ethylidene)-1,2-cyclohexanediamine; N-trityl-N-[(1R,2R)-2-[((E)-2-[[(1R,2R)-2-(tritylamino)cyclohexyl]imino]ethylidene)amino]cyclohexyl]amine | C52H54N4 | 详情 | 详情 | |
| (V) | 48513 | (1R,2R)-N(1)-trityl-N(2)-(2-[[(1R,2R)-2-(tritylamino)cyclohexyl]amino]ethyl)-1,2-cyclohexanediamine; N-trityl-N-[(1R,2R)-2-[(2-[[(1R,2R)-2-(tritylamino)cyclohexyl]amino]ethyl)amino]cyclohexyl]amine | C52H58N4 | 详情 | 详情 | |
| (VI) | 48514 | (1R,2R)-N(1)-(2-[[(1R,2R)-2-aminocyclohexyl]amino]ethyl)-1,2-cyclohexanediamine; N-[(1R,2R)-2-aminocyclohexyl]-N-(2-[[(1R,2R)-2-aminocyclohexyl]amino]ethyl)amine | C14H30N4 | 详情 | 详情 | |
| (VII) | 48515 | 2,6-Diacetylpyridine | 1129-30-2 | C9H9NO2 | 详情 | 详情 |
| (VIII) | 48516 | (4R,9R,14R,19R)-2,21-dimethyl-3,10,13,20,26-pentaazatetracyclo[20.3.1.0(4,9).0(14,19)]hexacosa-1(26),2,20,22,24-pentaene | C23H35N5 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(VII)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.
| 【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 |