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【结 构 式】 
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【分子编号】14610 【品名】4-Amino-TEMPO; 4-amino-2,2,6,6-tetramethyltetrahydro-1(2H)-pyridinol 【CA登记号】14691-88-4 |
【 分 子 式 】C9H19N2O 【 分 子 量 】171.26274 【元素组成】C 63.12% H 11.18% N 16.36% O 9.34% |
合成路线1
该中间体在本合成路线中的序号：(I)The condensation of 1-oxyl-2,2,6,6-tetramethyl-4-aminopiperidine (I) with 2-chloroethyl isocyanate (II) gives 1-(2-chloroethyl)-3-(1-oxyl-2,2,6,6-tetramethylpiperidinyl)urea (III). The nitrosation of (III) with dinitrogen tetraoxide in methylene chloride yields SLCNU.
| 【1】 Arai, Y.; Takeda, M.; Tsujihara, K.; Morikawa, T.; A new class of nitrosoureas. VII. Synthesis and antitumor activity of 3-substituted 1-(2-chloroethyl)-3-(methyl-alpha-D-glucopyranosid-3-yl)-1-nitrosoureas. Chem Pharm Bull 1982, 30, 4365. |
| 【2】 Li, S.W.; Sosnovsky, G.; SLCNU. Drugs Fut 1985, 10, 3, 211. |
| 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) | 14610 | 4-Amino-TEMPO; 4-amino-2,2,6,6-tetramethyltetrahydro-1(2H)-pyridinol | 14691-88-4 | C9H19N2O | 详情 | 详情 |
| (II) | 11237 | 1-Chloro-2-isocyanatoethane; 2-Chloroethyl isocyanate | 1943-83-5 | C3H4ClNO | 详情 | 详情 |
| (III) | 29078 | N-(2-chloroethyl)-N'-(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)urea | C12H23ClN3O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The nitrosation of (IV) with dinitrogen tetraoxide in methylene chloride affords (V), which is condensed with (I) to yield SLCNU.
| 【1】 Martinez, J.; Imbach, J.L.; Winternitz, F.; Oiry, J.; Activated N-nitrosocarbamates for regioselective synthesis of N-nitrosoureas. J Med Chem 1982, 25, 12, 178-182. |
| 【2】 Li, S.W.; Sosnovsky, G.; SLCNU. Drugs Fut 1985, 10, 3, 211. |
| 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) | 14610 | 4-Amino-TEMPO; 4-amino-2,2,6,6-tetramethyltetrahydro-1(2H)-pyridinol | 14691-88-4 | C9H19N2O | 详情 | 详情 |
| (IV) | 29079 | 1-([[(2-chloroethyl)amino]carbonyl]oxy)-2,5-pyrrolidinedione | C7H9ClN2O4 | 详情 | 详情 | |
| (V) | 29080 | 1-([[1-(2-chloroethyl)-2-oxohydrazino]carbonyl]oxy)-2,5-pyrrolidinedione | C7H8ClN3O5 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)Condensation of 1-oxyl-2,2,6,6-tetramethyl-4-aminopiperidine (I) with N,N-diaziridinyl phosphoryl urethane (II) gives SLDU.
合成路线4
该中间体在本合成路线中的序号：(III)Podophyllotoxin (I), isolated from the roots of Podophyllum emodi Wall var. chinensis sprague by extraction with ethanol and purified through repeated recrystallization from ethanol-benzene, is demethylated and brominated in a single step. (I) is suspended in a cold mixture of ethylene dichloride and ether. Anhydrous hydrogen bromide is passed until the calculated weight increase is reached. After standing at 0-2 C for 20 hours, the solvent is removed under reduced pressure. 4-Bromo-4-deoxy-4'-demethylepipodophyllotoxin (II) is recrystallized from acetone. A solution of (II) and 4-amino-2,2,6,6-tetramethylpiperidin-1-oxyl (III) with a trace of anhydrous pyridine in THF is refluxed under nitrogen atmosphere for 4 hours. The insoluble solid is removed by filtration and the solvent is distilled off under reduced pressure. The crude product is chromatographed twice through silica gel, using methylene chloride-acetone-diethylamine (40:1:1, by volume) as eluent. GP-7 is recrystallized from acetone-hexane.
| 【1】 Zhang, C.; Chen, Y.; Tian, X.; Spin-labeled antitumor derivatives of podophyllotoxin. Scientia Sin 1987, 30-B, 1070-9. |
| 【2】 Zhang, P.; Tian, X.; Li, J.; Wang, Y.; Chen, Y.; Jia, Z.; Anticancer drugs II. Synthesis and biological evaluation of spin labeled derivatives of podophyllotoxin. Life Sci 1989, 45, 26, 2569-75. |
| 【3】 Ruyun, J.; GP-7. Drugs Fut 1992, 17, 3, 191. |
| 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) | 14608 | (5R,5aR,8aR,9R)-9-hydroxy-5-(3,4,5-trimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one; Podophyllotoxin | 518-28-5 | C22H22O8 | 详情 | 详情 |
| (II) | 14609 | (5R,5aR,8aR,9S)-9-bromo-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one | C21H19BrO7 | 详情 | 详情 | |
| (III) | 14610 | 4-Amino-TEMPO; 4-amino-2,2,6,6-tetramethyltetrahydro-1(2H)-pyridinol | 14691-88-4 | C9H19N2O | 详情 | 详情 |