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【结 构 式】

【药物名称】

【化学名称】N-[5-[2-[1-[4-(2,4-Dioxothiazolidin-5-ylmethyl)phenyl]piperidin-4-ylamino]-1(R)-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide

【CA登记号】

【 分 子 式 】C24H30N4O6S2

【 分 子 量 】534.6579

【开发单位】Wyeth Pharmaceuticals (Originator)

【药理作用】Antidiabetic Drugs, Antiobesity Drugs, ENDOCRINE DRUGS, METABOLIC DRUGS, Treatment of Nutritional Disorders, Type 2 Diabetes Mellitus, Agents for, beta3-Adrenoceptor Agonists

合成路线1

The condensation of benzaldehyde (I) with thiazolidine-2,4-dione (II) by means of piperidine in ethanol gives the benzylidene-thiazolidinedione (III), which is reduced with H2 over Pd/C in methanol to yield the benzyl derivative (IV). The cleavage of the cyclic ketal group of (IV) with HCl affords the piperidone (V), which is finally reductocondensed with the chiral ethanolamine (VI) by means of sodium triacetoxyborohydride in DMF to provide the target compound. The intermediate ethanolamine (VI) has been obtained as follows: The reaction of 3-amino-4-(benzyloxy)acetophenone (VII) with Ms-Cl and pyridine in dichloromethane gives the expected sulfonamide (VIII), which is brominated with CuBr2 in chloroform to yield the phenacyl bromide (IX). Enantioselective reduction with the Corey's chiral oxazaborolidine catalyst affords the (R)-bromoethanol derivative (X), which is treated with NaN3 in DMSO to provide the azido compound (XI). Finally, this compound is reduced and debenzylated by hydrogenation with H2 over Pd/C in methanol to furnish the desired ethanolamine intermediate (VI).

1 Gunawan, I.; Ellingboe, J.; Hu, B.; et al.; 2,4-Thiazolidinediones as potent and selective human beta3 agonists. Bioorg Med Chem Lett 2001, 11, 6, 757.
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) 49400 4-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)benzaldehyde C14H17NO3 详情 详情
(II) 10883 1,3-Thiazolane-2,4-dione; 2,4-Thiazolidinedione 2295-31-0 C3H3NO2S 详情 详情
(III) 49401 5-[(E)-[4-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione C17H18N2O4S 详情 详情
(IV) 49402 5-[4-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)benzyl]-1,3-thiazolidine-2,4-dione C17H20N2O4S 详情 详情
(V) 49403 5-[4-(4-oxo-1-piperidinyl)benzyl]-1,3-thiazolidine-2,4-dione C15H16N2O3S 详情 详情
(VI) 49404 N-[5-[(1R)-2-amino-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide C9H14N2O4S 详情 详情
(VII) 20628 1-[3-amino-4-(benzyloxy)phenyl]-1-ethanone C15H15NO2 详情 详情
(VIII) 20629 N-[5-acetyl-2-(benzyloxy)phenyl]methanesulfonamide C16H17NO4S 详情 详情
(IX) 20630 N-[2-(benzyloxy)-5-(2-bromoacetyl)phenyl]methanesulfonamide C16H16BrNO4S 详情 详情
(X) 20634 N-[2-(benzyloxy)-5-[(1R)-2-bromo-1-hydroxyethyl]phenyl]methanesulfonamide C16H18BrNO4S 详情 详情
(XI) 49405 N-[5-[(1R)-2-azido-1-hydroxyethyl]-2-(benzyloxy)phenyl]methanesulfonamide C16H18N4O4S 详情 详情
Extended Information