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【结 构 式】 
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【分子编号】39104 【品名】diethyl 3-[(benzyloxy)[(4-methylphenyl)sulfonyl]amino]propylphosphonate 【CA登记号】 |
【 分 子 式 】C21H30NO6PS 【 分 子 量 】455.512102 【元素组成】C 55.37% H 6.64% N 3.07% O 21.07% P 6.8% S 7.04% |
合成路线1
该中间体在本合成路线中的序号：(XXVII)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：(VI)The title compound was originally isolated from the fermentation broths of Streptomyces rubellomurinus. The chemical synthesis of this compound was further described. Treatment of O-benzyl hydroxylamine (I) with TsCl in pyridine afforded N-(benzyloxy)-p-toluenesulfonamide (II). A closely related procedure used O-(p-methoxy-benzyl)hydroxylamine. Diethyl (3-bromopropyl)phosphonate (V) was obtained by alkylation of the sodium salt of diethyl phosphonate (III) with 1,3-dibromopropane (IV). Related procedures used dibutyl phosphonate or 1-bromo-3-chloropropane instead of (III) or (IV). The condensation of protected hydroxylamine (II) with bromide (V) in the presence of NaH furnished adduct (VI). Alternatively, intermediate (VI) was prepared by first alkylation of N-(benzyloxy)-p-toluenesulfonamide (II) with 1,3-dibromopropane (IV) to give (VII), and then condensation of bromide (VII) with the sodium salt of diethyl phosphonate (III). Hydrolysis of (VI) with HCl in HOAc gave rise to 3-(N-hydroxyamino)propylphosphonic acid (VIII). This was finally acetylated with Ac2O in NaOH.
| 【1】 Takashi, K.; et al.; Studies on phosphonic acid antibiotics. I. Structure and synthesis 3-(N-acetyl-N-hydroxyamino) propylphosphonic acid (FR-900098) and its N-formyl analog (FR-31564). Tetrahedron Lett 1980, 21, 1, 95. |
| 【2】 Iguchi, E.; et al.; Studies on new phosphonic acid antibiotics II. Taxonomic studies on producing organisms of the phosphonic acid and related compounds. J Antibiot 1980, 33, 1, 18. |
| 【3】 Takeno, H.; Hemmi, K.; Hashimoto, M.; Kamiya, T. (Fujisawa Pharmaceutical Co., Ltd.); Hydroxyaminohydrocarbonphosphonic acids. DE 2733658; US 4182758; US 4206156 . |
| 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) | 14640 | O-benzylhydroxylamine; 1-[(aminooxy)methyl]benzene | 622-33-3 | C7H9NO | 详情 | 详情 |
| (II) | 39517 | N-(benzyloxy)-4-methylbenzenesulfonamide | C14H15NO3S | 详情 | 详情 | |
| (III) | 12714 | diethyl phosphonate; diethyl phosphite | 762-04-9 | C4H11O3P | 详情 | 详情 |
| (IV) | 12581 | 1,3-Dibromopropane | 109-64-8 | C3H6Br2 | 详情 | 详情 |
| (V) | 39080 | diethyl 3-bromopropylphosphonate | C7H16BrO3P | 详情 | 详情 | |
| (VI) | 39104 | diethyl 3-[(benzyloxy)[(4-methylphenyl)sulfonyl]amino]propylphosphonate | C21H30NO6PS | 详情 | 详情 | |
| (VII) | 39517 | N-(benzyloxy)-4-methylbenzenesulfonamide | C14H15NO3S | 详情 | 详情 | |
| (VIII) | 39088 | 3-(hydroxyamino)propylphosphonic acid | C3H10NO4P | 详情 | 详情 |