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【结 构 式】 
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【分子编号】31437 【品名】ethyl 4-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-5-methylphenoxy]butanoate 【CA登记号】 |
【 分 子 式 】C21H21NO5 【 分 子 量 】367.40148 【元素组成】C 68.65% H 5.76% N 3.81% O 21.77% |
合成路线1
该中间体在本合成路线中的序号：(V)Protection of 3-amino-5-methylphenol (I) with phthalic anhydride (II) provided the phthalimido derivative (III), which was alkylated with ethyl 4-bromobutyrate (IV) in the presence of K2CO3 to give the corresponding ether (V). Hydrazinolysis of the phthalimido group of (V) afforded the primary amine (VI), which was condensed with benzenesulfonyl chloride (VII), yielding sulfonamide (VIII). Saponification of the ethyl ester of (VIII) gave carboxylic acid (IX). After conversion to the mixed anhydride with isobutyl chloroformate and N-methylmorpholine, treatment with methanolic ammonia furnished amide (X). This was reduced to amine (XI) using LiAlH4 in THF. Finally, reaction of (XI) with S-methylisothiouronium sulfate (XII) in refluxing EtOH provided the target guanidine.
| 【1】 Weber, I.R.; Neidlein, R.; von der Saal, W.; Grams, F.; Leinert, H.; Strein, K.; Engh, R.A.; Kucznierz, R.; Diarylsulfonamides as selective, non-peptidic thrombin inhibitors. Bioorg Med Chem Lett 1998, 8, 13, 1613. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II)) | 11900 | 2-Benzofuran-1,3-dione;1,2-Benzenedicarboxylic Anhydride;1,2-BENZENE DICARBOXYLIC ACID ANHYDRIDE;1,2-BENZENEDICARBONIC ACID, ANHYDRIDE;1,3-DIOXOPHTHALAN;1,3-ISOBENZOFURANDIONE;o-phthalic anhydride; Phthalic anhydride | 85-44-9 | C8H4O3 | 详情 | 详情 |
| (I) | 31435 | 3-amino-5-methylphenol | C7H9NO | 详情 | 详情 | |
| (III) | 31436 | 2-(3-hydroxy-5-methylphenyl)-1H-isoindole-1,3(2H)-dione | C15H11NO3 | 详情 | 详情 | |
| (IV) | 11263 | ethyl 4-bromobutanoate; Ethyl 4-bromobutyrate | 2969-81-5 | C6H11BrO2 | 详情 | 详情 |
| (V) | 31437 | ethyl 4-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-5-methylphenoxy]butanoate | C21H21NO5 | 详情 | 详情 | |
| (VI) | 31438 | ethyl 4-(3-amino-5-methylphenoxy)butanoate | C13H19NO3 | 详情 | 详情 | |
| (VII) | 14713 | benzenesulfonyl chloride | 98-09-9 | C6H5ClO2S | 详情 | 详情 |
| (VIII) | 31439 | ethyl 4-[3-methyl-5-[(phenylsulfonyl)amino]phenoxy]butanoate | C19H23NO5S | 详情 | 详情 | |
| (IX) | 31441 | 4-[3-methyl-5-[(phenylsulfonyl)amino]phenoxy]butyric acid | C17H19NO5S | 详情 | 详情 | |
| (X) | 31440 | 4-[3-methyl-5-[(phenylsulfonyl)amino]phenoxy]butanamide | C17H20N2O4S | 详情 | 详情 | |
| (XI) | 31442 | N-[3-(4-aminobutoxy)-5-methylphenyl]benzenesulfonamide | C17H22N2O3S | 详情 | 详情 | |
| (XII) | 10272 | [[Amino(imino)methyl]sulfanyl]methane | 2986-19-8 | C2H6N2S | 详情 | 详情 |