【结 构 式】 |
【药物名称】 【化学名称】2,5-Dihydroxy-3-(1-methylindol-3-yl)-6-phenyl-2,5-cyclohexadiene-1,4-dione 【CA登记号】245737-50-2 【 分 子 式 】C21H15NO4 【 分 子 量 】345.358 |
【开发单位】Merck & Co. (Originator) 【药理作用】Antidiabetic Drugs, ENDOCRINE DRUGS, Insulin Receptor Agonists, Insulin Sensitizers |
合成路线1
Treatment of phenylacetyl chloride (I) with tris(trimethylsilyloxy)ethylene (A) in the presence of SnCl4 affords 1-hydroxy-3-phenylpropan-2-one (II), which is then condensed with ethyl oxalyl chloride (III) in THF in the presence of Et3N to yield (IV). Phenylhexanoate derivative (IV) is cyclized by means of DBU in DMF to provide valerolactone derivative (V), which is then condensed with 1-methylindole-3-carboxaldehyde (VI) in HOAc to furnish derivative (VII). Finally, the target compound is obtained by treatment of (VII) with NaOMe in MeOH.
【1】 Liu, K.; Szalkowski, D.; Xu, L.; et al.; Discovery of a potent, highly selective, and orally efficacious small-molecule activator of the insulin receptor. J Med Chem 2000, 43, 19, 3487. |
【2】 Wood, H.B.; Jones, A.B.; Zhang, B.; Liu, K. (Merck & Co., Inc.); Antidiabetic agents. EP 1067925; US 6077849; WO 9951225 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(A) | 14534 | 2,2,7,7-tetramethyl-4-[(trimethylsilyl)oxy]-3,6-dioxa-2,7-disila-4-octene; 1,2-bis[(trimethylsilyl)oxy]vinyl trimethylsilyl ether; TRIS(TRIMETHYLSILYLOXY)ETHYLENE | 69097-20-7 | C11H28O3Si3 | 详情 | 详情 |
(I) | 25890 | 2-phenylacetyl chloride;Phenylacetyl chloride;Phenacetyl chloride;Benzeneacetyl chloride | 103-80-0 | C8H7ClO | 详情 | 详情 |
(II) | 45469 | 2-phenylethaneperoxoic acid | C8H8O3 | 详情 | 详情 | |
(III) | 11043 | Ethyl 2-chloro-2-oxoacetate; Ethyl oxalyl chloride | 4755-77-5 | C4H5ClO3 | 详情 | 详情 |
(IV) | 45470 | ethyl 2-oxo-2-[(2-phenylacetyl)peroxy]acetate | C12H12O6 | 详情 | 详情 | |
(V) | 45471 | 3-hydroxy-4-phenyl-2H-pyran-2,5(6H)-dione | C11H8O4 | 详情 | 详情 | |
(VI) | 45472 | 1-Methylindole-3-carboxaldehyde; 1-Methyl-1H-indole-3-carbaldehyde; 1-Methylindole-3-carbaldehyde | 19012-03-4 | C10H9NO | 详情 | 详情 |
(VII) | 45473 | 3-hydroxy-6-[(Z)-(3-methyl-3H-benzimidazol-1-yl)methylidene]-4-phenyl-2H-pyran-2,5-dione | 455-15-2 | C20H16N2O4 | 详情 | 详情 |