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【结 构 式】 
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【药物名称】DIBRT 【化学名称】3,5-Dibromo-4-(4-hydroxy-3,5-diisopropylphenoxy)benzoic acid 【CA登记号】192766-84-0 【 分 子 式 】C19H20Br2O4 【 分 子 量 】472.17685 |
【开发单位】Karo Bio (Originator), University of California, San Francisco (Originator) 【药理作用】ENDOCRINE DRUGS, Thyroid Disease Therapy, Antithyroid Drugs |
合成路线1
Methylation of 2,6-diisopropylphenol (I) with iodomethane and K2CO3 provides ether (II). Subsequent treatment with iodine and nitric acid gives rise to the diaryl iodonium compound (III), isolated as the corresponding tetrafluoroborate salt. 3,5-Dibromo-4-hydroxybenzoic acid (IV) is esterified with methanol and thionyl chloride to produce (V). Copper-promoted coupling between hydroxybenzoate (V) and the diaryl iodonium salt (III) leads to diaryl ether (VI). Finally, simultaneous cleavage of the methyl ether and ester groups of (VI) is achieved by means of boron tribromide in cold CH2Cl2
| 【1】 Baxter, J.D.; Goede, P.; Apriletti, J.W.; et al.; Structure-based design and synthesis of a thyroid hormone receptor (TR) antagonist. Endocrinology 2002, 143, 2, 517. |
| 【2】 Baxter, J.D.; Scanlan, T.S.; Fletterick, R.J.; Wagner, R.L.; Kushner, P.J.; West, B.L.; Shiau, A.K.; Apriletti, J.W. (University of California, Oakland); Nuclear receptor ligands and ligand binding domains. CA 2314096; EP 1034184; US 6266622; WO 9926966 . |
| 【3】 Brenneisen,P.; et al. (Ciba Geigy Corp.); Nuclear receptor ligands and ligand binding domains. DE 1932690; DE 1935338; US 3839582 . |
| 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) | 20249 | 2,6-Diisopropylphenol | 2078-54-8 | C12H18O | 详情 | 详情 |
| (II) | 60874 | 2,6-diisopropylphenyl methyl ether; 1,3-diisopropyl-2-methoxybenzene | C13H20O | 详情 | 详情 | |
| (III) | 60875 | bis(3,5-diisopropyl-4-methoxyphenyl)iodonium | C26H38IO2 | 详情 | 详情 | |
| (IV) | 10115 | 3,5-Dibromo-4-hydroxybenzoic acid | 3337-62-0 | C7H4Br2O3 | 详情 | 详情 |
| (V) | 10116 | methyl 3,5-dibromo-4-hydroxybenzoate | 41727-47-3 | C8H6Br2O3 | 详情 | 详情 |
| (VI) | 60876 | methyl 3,5-dibromo-4-(3,5-diisopropyl-4-methoxyphenoxy)benzoate | C21H24Br2O4 | 详情 | 详情 |