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【结 构 式】 
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【药物名称】SR-4895 【化学名称】3-Ethyl-1,2,4-benzotriazine-1,4-dioxide 【CA登记号】166182-17-8 【 分 子 式 】C9H9N3O2 【 分 子 量 】191.19098 |
【开发单位】SRI (Originator) 【药理作用】ONCOLYTIC DRUGS |
合成路线1
The reaction of phenylhydrazine (I) with propionaldehyde (II) gives the corresponding hydrazone (III), which is condensed with phenyldiazoninum chloride (IV) to yield the formazan (V). The cyclization of (V) by means of BF3 in hot acetic acid affords 3-ethyl-1,2,4-benzotriazine (VI), which is finally oxidized to the target dioxide by means of H2O2 and trifluoroacetic anhydride in dichloromethane.
| 【1】 Kelson, A.B.; et al.; 1,2,4-Benzotriazine 1,4-dioxides. An important class of hypoxic cytotoxins with antitumor activity. Anti-Cancer Drug Des 1998, 13, 6, 575. |
| 【2】 Brown, M.J. (Leland Stanford Junior University); Method of tumor treatment. EP 0649658 . |
| 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) | 11818 | Phenyl hydrazine; 1-Phenylhydrazine | 100-63-0 | C6H8N2 | 详情 | 详情 |
| (II) | 15966 | propionaldehyde | 123-38-6 | C3H6O | 详情 | 详情 |
| (III) | 25896 | propanal N-phenylhydrazone | C9H12N2 | 详情 | 详情 | |
| (IV) | 25897 | benzenediazonium chloride | C6H5ClN2 | 详情 | 详情 | |
| (V) | 25898 | 1-[(E)-2-phenyldiazenyl]-1-propanone N-phenylhydrazone | C15H16N4 | 详情 | 详情 | |
| (VI) | 25899 | 3-ethyl-1,2,4-benzotriazine | C9H9N3 | 详情 | 详情 |
合成路线2
The reaction of 2-nitroaniline (I) with cyanamide and HCl at 100 C, followed by a treatment with NaOH at the same temperature gives the benzotriazine N-oxide (II), which is diazotized with NaNO2 and HCl, followed by a treatment with POCl3 and dimethylaniline to yield the chloro derivative (III). The reaction of (III) with tetraethyltin and Pd(PPh3)4 in hot DME affords the ethyl derivative (IV), which is finally oxidized with trifluoroperacetic acid in dichloromethane to provide the target N1, N4-bis oxide compound.
| 【1】 Hay, M.P.; Denny, W.A.; New and versatile syntheses of 3-alkyl- and 3-aryl-1,2,4-benzotriazine 1,4-dioxides: Preparation of the bioreductive cytotoxins SR 4895 and SR 4941. Tetrahedron Lett 2002, 43, 52, 9569. |
| 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) | 11608 | o-Nitroaniline; 2-Nitroaniline; 2-Nitrophenylamine | 88-74-4 | C6H6N2O2 | 详情 | 详情 |
| (II) | 11609 | 3-amino-1,2,4-benzotriazin-1-ium-1-olate; 3-Amino-1,2,4-benzotriazine-1-oxide | 5424-06-6 | C7H6N4O | 详情 | 详情 |
| (III) | 11611 | 3-chloro-1,2,4-benzotriazin-1-ium-1-olate | C7H4ClN3O | 详情 | 详情 | |
| (IV) | 62231 | 3-ethyl-1,2,4-benzotriazin-1-ium-1-olate | C9H9N3O | 详情 | 详情 |