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【结 构 式】 
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【分子编号】39105 【品名】3-bromopropylphosphonic acid 【CA登记号】1190-09-6 |
【 分 子 式 】C3H8BrO3P 【 分 子 量 】202.972482 【元素组成】C 17.75% H 3.97% Br 39.37% O 23.65% P 15.26% |
合成路线1
该中间体在本合成路线中的序号：(XXVIII)10) The condensation of diethyl phosphonate (III) with N-(p-methoxybenzyloxy)-N-(3-chloropropyl)-p-toluenesulfonamide (XXV) by means of NaH in refluxing benzene gives (VIII), which is hydrolyzed with HCl in acetic acid to obtain compound (I). 11) The condensation of (III) with N-(3-chloropropyl)-N-(benzyloxy)-p-toluenesulfonamide (XXVI) by means of NaH in refluxing benzene gives diethyl 3-(N-benzyloxy-N-tosylamino)propylphosphonate (XXVII), which is hydrolyzed with HCl in acetic acid to obtain compound (I). 12) By reaction of 3-bromopropylphosphonic acid (XXVIII) with hydroxylamine by means of sodium methoxide in MeOH to obtain compound (I).
| 【1】 Kuroda, Y.; et al.; US 4143135 . |
| 【2】 Prous, J.R.; Castaner, J.; FR-31564. Drugs Fut 1980, 5, 5, 239. |
| 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) | 39088 | 3-(hydroxyamino)propylphosphonic acid | C3H10NO4P | 详情 | 详情 | |
| (III) | 12714 | diethyl phosphonate; diethyl phosphite | 762-04-9 | C4H11O3P | 详情 | 详情 |
| (VIII) | 39087 | diethyl 3-[[(4-methoxybenzyl)oxy][(4-methylphenyl)sulfonyl]amino]propylphosphonate | C22H32NO7PS | 详情 | 详情 | |
| (XXV) | 39102 | N-(3-chloropropyl)-N-[(4-methoxybenzyl)oxy]-4-methylbenzenesulfonamide | C18H22ClNO4S | 详情 | 详情 | |
| (XXVI) | 39103 | N-(benzyloxy)-N-(3-chloropropyl)-4-methylbenzenesulfonamide | C17H20ClNO3S | 详情 | 详情 | |
| (XXVII) | 39104 | diethyl 3-[(benzyloxy)[(4-methylphenyl)sulfonyl]amino]propylphosphonate | C21H30NO6PS | 详情 | 详情 | |
| (XXVIII) | 39105 | 3-bromopropylphosphonic acid | 1190-09-6 | C3H8BrO3P | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)The reaction of 1,3-dibromopropane (I) with triethyl phosphite (II) at 160 C gives triethyl 3-bromopropylphosphonate (III), which is treated with Tms-Br and water to yield the corresponding phosphonic acid (IV). The reaction of (IV) with PCl3 in refluxing chloroform affords the acyl chloride (V), which is treated with 4-methoxyphenol (VI) and pyridine to provide the expected 4-methoxyphenyl diester (VII). The reaction of (VII) with N,O-bis(tert-butoxycarbonyl)hydroxylamine (VIII) by means of NaH in DMF gives the fully protected hydroxyamino derivative (IX), which by treatment with TFA in dichloromethane yields 3-(hydroxyamino)propylphosphonic acid 4-methoxyphenyl diester (X). Finally, this compound is acylated with Ac-Cl and TEA in ethyl ether to afford the target N-acetylhydroxyamino compound.
| 【1】 Reichenberg, A.; et al.; Diaryl ester prodrugs of FR900098 with improved in vivo antimalarial activity. Bioorg Med Chem Lett 2001, 11, 6, 833. |
| 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) | 12581 | 1,3-Dibromopropane | 109-64-8 | C3H6Br2 | 详情 | 详情 |
| (II) | 15487 | triethyl phosphite | 122-52-1 | C6H15O3P | 详情 | 详情 |
| (III) | 39080 | diethyl 3-bromopropylphosphonate | C7H16BrO3P | 详情 | 详情 | |
| (IV) | 39105 | 3-bromopropylphosphonic acid | 1190-09-6 | C3H8BrO3P | 详情 | 详情 |
| (V) | 49412 | 3-bromopropylphosphonic dichloride | C3H6BrCl2OP | 详情 | 详情 | |
| (VI) | 32744 | 4-methoxyphenol | 150-76-5 | C7H8O2 | 详情 | 详情 |
| (VII) | 49413 | bis(4-methoxyphenyl) 3-bromopropylphosphonate | C17H20BrO5P | 详情 | 详情 | |
| (VIII) | 34722 | 2-[([[(tert-butoxycarbonyl)amino]oxy]carbonyl)oxy]-2-methylpropane | C10H19NO5 | 详情 | 详情 | |
| (IX) | 49414 | 5-(tert-butoxycarbonyl)-1,1-bis(4-methoxyphenoxy)-9,9-dimethyl-1,7-dioxo-6,8-dioxa-5-aza-1lambda(5)-phosphadecane | C27H38NO10P | 详情 | 详情 | |
| (X) | 49415 | bis(4-methoxyphenyl) 3-(hydroxyamino)propylphosphonate | C17H22NO6P | 详情 | 详情 |