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【结 构 式】

【分子编号】13449

【品名】4-(5,6,7,8-Tetrahydroimidazo[1,5-a]pyridin-5-yl)benzamide

【CA登记号】

【 分 子 式 】C14H15N3O

【 分 子 量 】241.29272

【元素组成】C 69.69% H 6.27% N 17.41% O 6.63%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(X)

A new synthesis of fadrozole hydrochloride has been published: The oxidation of 4-(2-pyridyl)benzoic acid ethyl ester (I) with peracetic acid at 90 C gives the corresponding N-oxide (II), which by reaction with dimethyl sulfate and potassium cyanide yields 4-(6-cyano-2-pyridyl)benzoic acid ethyl ester (III). The hydrogenation of (III) with H2 over Pd/C in methanol affords 4-[6-(aminomethyl)-2-pyridyl]benzoic acid ethyl ester (IV), which is formylated with formic acid at 90 C, giving the formamido derivative (V). The cyclization of (V) by means of POCl3 in toluene at 90 C yields 4-(imidazo[1,5-a]pyridin-5-yl)benzoic acid ethyl ester (VI), which is hydrogenated with H2 over Pd/C in anhydrous ethanol containing HCl to afford 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzoic acid ethyl ester (VII). The hydrolysis of (VI) with NaOH in ethanol gives the corresponding acid (VIII), which by reaction with refluxing SOCl2 yields the acyl chloride (IX). The reaction of (IX) with dry ammonia in dichloromethane affords the 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzamide (X), which is finally treated with POCl3 in refluxing chloroform. The final product is obtained by treatment with dry HCl in ethylether.

1 Gude, C.; Rodriguez, H.; Steele, R.E.; Browne, L.J.; Fadrozole hydrochloride: A potent, selective, nonsteroidal inhibitor of aromatase for the treatment of estrogen-dependent disease. J Med Chem 1991, 34, 2, 725-36.
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) 13440 ethyl 4-(2-pyridinyl)benzoate C14H13NO2 详情 详情
(II) 13441 2-[4-(ethoxycarbonyl)phenyl]-1-pyridiniumolate C14H13NO3 详情 详情
(III) 13442 ethyl 4-(6-cyano-2-pyridinyl)benzoate C15H12N2O2 详情 详情
(IV) 13443 ethyl 4-[6-(aminomethyl)-2-pyridinyl]benzoate C15H16N2O2 详情 详情
(V) 13444 ethyl 4-[6-[(formylamino)methyl]-2-pyridinyl]benzoate C16H16N2O3 详情 详情
(VI) 13445 ethyl 4-imidazo[1,5-a]pyridin-5-ylbenzoate C16H14N2O2 详情 详情
(VII) 13446 ethyl 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzoate C16H18N2O2 详情 详情
(VIII) 13447 4-(5,6,7,8-Tetrahydroimidazo[1,5-a]pyridin-5-yl)benzoic acid C14H14N2O2 详情 详情
(IX) 13448 4-(5,6,7,8-Tetrahydroimidazo[1,5-a]pyridin-5-yl)benzoyl chloride C14H13ClN2O 详情 详情
(X) 13449 4-(5,6,7,8-Tetrahydroimidazo[1,5-a]pyridin-5-yl)benzamide C14H15N3O 详情 详情
Extended Information