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【结 构 式】 
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【分子编号】46249 【品名】diethyl 1,7-bis[(2-nitrophenyl)sulfonyl]-1,4,7-triazacyclotetradecan-4-ylphosphonate 【CA登记号】 |
【 分 子 式 】C27H40N5O11PS2 【 分 子 量 】705.747462 【元素组成】C 45.95% H 5.71% N 9.92% O 24.94% P 4.39% S 9.09% |
合成路线1
该中间体在本合成路线中的序号：(V)The acylation of 1,7-heptanediamine (I) with 2-nitrobenzenesulfonyl chloride (II) by means of TEA in dichloromethane gives the bis sulfamide (III), which is submitted to macrocyclization with the dimesylate (IV) by means of Cs2CO3 in hot DMF, yielding the protected 1,4,7-triazacyclotetradecane (V). The cleavage of the phosphoryl group of (IV) with HBr in acetic acid affords the secondary amine (VI), which is alkylated with he benzyl chloride (VII) by means of K2CO3 in refluxing acetonitrile, providing the adduct (VIII). This compound is deprotected with K2CO3 in DMF and treated with HCl or HBr to furnish the corresponding target salts.
| 【2】 Bogucki, D.E.; Boehringer, E.M.; Wang, Z.; Bridger, G.J.; Schols, D.; Skerlj, R.T. (AnorMED Inc.); Antiviral macrocyclic cpds.. EP 1095031; WO 0002870 . |
| 【1】 De Clercq, E.; HEnson, G.; Schols, D.; Witvrouw, M.; Macfarland, R.T.; Bridger, G.J.; Skerli, R.T.; Yasuda, N.; An orally bioavailable CXCR4 antagonist for inhibition of HIV replication. 40th Intersci Conf Antimicrob Agents Chemother (Sept 17 2000, Toronto) 2000, Abst F-1845. |
| 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) | 12941 | 7-Aminoheptylamine; 1,7-Diaminoheptane; 1,7-Heptanediamine | 646-19-5 | C7H18N2 | 详情 | 详情 |
| (II) | 32624 | 2-Nitrobenzenesulfonyl chloride | 1694-92-4 | C6H4ClNO4S | 详情 | 详情 |
| (III) | 46248 | 2-nitro-N-(7-[[(2-nitrophenyl)sulfonyl]amino]heptyl)benzenesulfonamide | C19H24N4O8S2 | 详情 | 详情 | |
| (IV) | 34634 | 2-((diethoxyphosphoryl)[2-[(methylsulfonyl)oxy]ethyl]amino)ethyl methanesulfonate | C10H24NO9PS2 | 详情 | 详情 | |
| (V) | 46249 | diethyl 1,7-bis[(2-nitrophenyl)sulfonyl]-1,4,7-triazacyclotetradecan-4-ylphosphonate | C27H40N5O11PS2 | 详情 | 详情 | |
| (VI) | 46250 | 1,7-bis[(2-nitrophenyl)sulfonyl]-1,4,7-triazacyclotetradecane | C23H31N5O8S2 | 详情 | 详情 | |
| (VII) | 46251 | N-[4-(chloromethyl)benzyl]-2-nitro-N-(2-pyridinylmethyl)benzenesulfonamide | C20H18ClN3O4S | 详情 | 详情 | |
| (VIII) | 46252 | N-[4-([1,7-bis[(2-nitrophenyl)sulfonyl]-1,4,7-triazacyclotetradecan-4-yl]methyl)benzyl]-2-nitro-N-(2-pyridinylmethyl)benzenesulfonamide | C43H48N8O12S3 | 详情 | 详情 |