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【结 构 式】 
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【分子编号】62867 【品名】5-ethyl-2-[2-(4-nitrophenoxy)ethyl]pyridine; 2-(5-ethyl-2-pyridinyl)ethyl 4-nitrophenyl ether 【CA登记号】 |
【 分 子 式 】C15H16N2O3 【 分 子 量 】272.30372 【元素组成】C 66.16% H 5.92% N 10.29% O 17.63% |
合成路线1
该中间体在本合成路线中的序号：(III)The condensation of 2-(5-ethyl-2-pyridyl)ethanol (I) with 4-fluoronitrobenzene (II) by means of NaH in DMF gives 4-[2-(5-ethyl-2-pyridyl)ethoxy]nitrobenzene (III), which is reduced with H2 over Pd/C in methanol to yield the corresponding aniline (IV). The reaction of (IV) with NaNO2/HBr and methyl acrylate (V) in acetone/methanol affords the 2-bromopropionate derivative (VI), which is cyclized with thiourea (VII) by means of NaOAc in refluxing ethanol to provide the 2-imino-4-thiazolidinone (VIII). Finally, this compound is hydrolyzed with refluxing 2N HCl.
| 【1】 Meguro, K.; Fujita, T. (Takeda Chemical Industries, Ltd.); Thiazolidinedione derivs., their production and use. EP 0193256; ES 8705886; JP 1986267580; US 4687777 . |
| 【2】 Sohda, T.; Momose, Y.; Meguro, K.; Kawamatsu, Y.; Sugiyama, Y.; Ikeda, H.; Studies on antidiabetic agents. Synthesis and hypoglycemic activity of 5-[4-(pyridylalkoxy)benzyl]-2,4-thiazolidinediones. Arzneim-Forsch Drug Res 1990, 40, 1, 37. |
| 【3】 Prous, J.; Castaner, J.; PIOGLITAZONE HYDROCHLORIDE < Prop INNM; USAN >. Drugs Fut 1990, 15, 11, 1080. |
| 【4】 Meguro, K.; Momose, Y.; Sohda, T.; Oi, S.; Ikeda, H.; Hatanaka, C.; Studies on antidiabetic agents. X. Synthesis and biological activities of pioglitazone and related compounds. Chem Pharm Bull 1991, 39, 6, 1440-5. |
| 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) | 14139 | 2-(5-Ethyl-2-pyridinyl)-1-ethanol | 5223-06-3 | C9H13NO | 详情 | 详情 |
| (II) | 14153 | 4-Fluoronitrobenzene; 1-Fluoro-4-nitrobenzene | 350-46-9 | C6H4FNO2 | 详情 | 详情 |
| (III) | 62867 | 5-ethyl-2-[2-(4-nitrophenoxy)ethyl]pyridine; 2-(5-ethyl-2-pyridinyl)ethyl 4-nitrophenyl ether | C15H16N2O3 | 详情 | 详情 | |
| (IV) | 62868 | 4-[2-(5-ethyl-2-pyridinyl)ethoxy]aniline; 4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenylamine | C15H18N2O | 详情 | 详情 | |
| (V) | 14156 | methyl acrylate | 96-33-3 | C4H6O2 | 详情 | 详情 |
| (VI) | 62869 | methyl 2-bromo-3-{4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl}propanoate | C19H22BrNO3 | 详情 | 详情 | |
| (VII) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |
| (VIII) | 62870 | 5-{4-[2-(5-ethyl-2-pyridinyl)ethoxy]benzyl}-2-imino-1,3-thiazolidin-4-one | C19H21N3O2S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)
| 【1】 R4jendra GL, Pang NG, Maya JS, et al. 2004. Improved process for preparation of thiazolidinedione derivatives. W0 2004024059 |
| 【2】 Sohda T, Momose Y, Meguro K, et al. 1990. Studies on antidiabetic agents Synthesis and hypoglycemic activity of 5-[4-(pyridylaIkoxy) benzyl]-2,4-thiazolidinediones. Arzneim-Forsch, 40: 37～42 |
| 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) | 62866 | 2-(5-ethyl-2-pyridinyl)ethyl methanesulfonate | C10H15NO3S | 详情 | 详情 | |
| (II) | 11236 | 4-Nitrophenol; p-Nitrophenol | 100-02-7 | C6H5NO3 | 详情 | 详情 |
| (III) | 62867 | 5-ethyl-2-[2-(4-nitrophenoxy)ethyl]pyridine; 2-(5-ethyl-2-pyridinyl)ethyl 4-nitrophenyl ether | C15H16N2O3 | 详情 | 详情 | |
| (IV) | 62868 | 4-[2-(5-ethyl-2-pyridinyl)ethoxy]aniline; 4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenylamine | C15H18N2O | 详情 | 详情 | |
| (V) | 66597 | 4-(2-(5-ethylpyridin-2-yl)ethoxy)benzenediazonium | C15H16N3O | 详情 | 详情 | |
| (VI) | 14156 | methyl acrylate | 96-33-3 | C4H6O2 | 详情 | 详情 |
| (VII) | 66598 | methyl 3-(4-(2-(5-ethylpyridin-2-yl)ethoxy)phenyl)propanoate | C19H23NO3 | 详情 | 详情 |