|
【结 构 式】 
|
【分子编号】36909 【品名】2-(2-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]ethoxy)-1H-isoindole-1,3(2H)-dione 【CA登记号】 |
【 分 子 式 】C20H16N2O6S 【 分 子 量 】412.42292 【元素组成】C 58.25% H 3.91% N 6.79% O 23.28% S 7.78% |
合成路线1
该中间体在本合成路线中的序号：(IX)This compound has been obtained by two related ways: 1) The condensation of 4-acetylbiphenyl oxime (I) with 2-(2-bromoethoxy)tetrahydropyran (II) by means of K2CO3 in hot dimethylacetamide gives the oxime derivative (III), which is treated with TsOH in methanol yielding 4-acetylbiphenyl O-(2-hydroxyethyl)oxime (IV). The condensation of (IV) with 5-(4-hydroxybenzyl)-3-tritylthiazolidine-2,4-dione (V) by means of diethyl azodicarboxylate (DEAD) and PPh3 in THF affords (VI), the trityl derivative of the target compound, which is finally treated with hot aqueous ethanol to eliminate the trityl group. 2) The condensation of 5-(4-hydroxybenzyl)thiazolidine-2,4-dione (VIII) with N-(2-hydroxyethoxy)phthalimide (VII) by means DEAD gives the adduct (IX), which is treated with hydrazine to eliminate the phthalimido group yielding the substituted hydroxylamine (X). Finally, this compound is condensed with 4-acetylbiphenyl (XI) by means of TEA.
| 【1】 Yanagisawa, H.; Fujita, T.; Fujimoto, K.; Yoshioka, T.; Wada, K.; Oguchi, M.; Fujiwara, T.; Horikoshi, H. (Sankyo Co., Ltd.); Oxime derivs., their preparation and their therapeutic use. CA 2159938; EP 0708098; JP 1997048779; US 5703096; US 5780490; US 5972959 . |
| 【2】 Isobe, A.; Fujita, S.; Fujiwara, T.; Yanagisawa, H.; Takamura, M.; Yamada, E.; Hagisawa, Y.; Yachi, M.; Novel oximes having 5-benzyl-2,4-thiazolidinedione as antihyperglycemic agents: Synthesis and structure-activity relationship. Bioorg Med Chem Lett 2000, 10, 4, 373. |
| 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) | 36912 | 1-[1,1'-biphenyl]-4-yl-1-ethanone oxime | C14H13NO | 详情 | 详情 | |
| (II) | 26934 | 2-bromoethyl tetrahydro-2H-pyran-2-yl ether | C7H13BrO2 | 详情 | 详情 | |
| (III) | 36913 | 1-[1,1'-biphenyl]-4-yl-1-ethanone O-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]oxime | C21H25NO3 | 详情 | 详情 | |
| (IV) | 36914 | 1-[1,1'-biphenyl]-4-yl-1-ethanone O-(2-hydroxyethyl)oxime | C16H17NO2 | 详情 | 详情 | |
| (V) | 18803 | 5-(4-hydroxybenzyl)-3-trityl-1,3-thiazolidine-2,4-dione | C29H23NO3S | 详情 | 详情 | |
| (VI) | 36915 | 5-[4-[2-([[(E)-1-[1,1'-biphenyl]-4-ylethylidene]amino]oxy)ethoxy]benzyl]-3-trityl-1,3-thiazolidine-2,4-dione | C45H38N2O4S | 详情 | 详情 | |
| (VII) | 36908 | 2-(2-hydroxyethoxy)-1H-isoindole-1,3(2H)-dione | C10H9NO4 | 详情 | 详情 | |
| (VIII) | 26462 | 5-(4-hydroxybenzyl)-1,3-thiazolidine-2,4-dione | 74772-78-4 | C10H9NO3S | 详情 | 详情 |
| (IX) | 36909 | 2-(2-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]ethoxy)-1H-isoindole-1,3(2H)-dione | C20H16N2O6S | 详情 | 详情 | |
| (X) | 36910 | 5-[4-[2-(aminooxy)ethoxy]benzyl]-1,3-thiazolidine-2,4-dione | C12H14N2O4S | 详情 | 详情 | |
| (XI) | 36916 | 1-[1,1'-biphenyl]-4-yl-1-ethanone | 92-91-1 | C14H12O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)This compound has been obtained by two related ways: 1) The condensation of 3-acetyl-6-phenylpyridine oxime (I) with 2-(2-bromoethoxy)tetrahydropyran (II) by means of K2CO3 in hot dimethylacetamide gives the oxime derivative (III), which is treated with TsOH in methanol yielding 3-acetyl-6-phenylpyridine O-(2-hydroxyethyl)oxime (IV). The condensation of (IV) with 5-(4-hydroxybenzyl)-3-tritylthiazolidine-2,4-dione (V) by means of diethyl azodicarboxylate (DEAD) and PPh3 in THF affords (VI), the trityl derivative of the target compound, which is finally treated with hot aqueous ethanol to eliminate the trityl group. 2) The condensation of 5-(4-hydroxybenzyl)thiazolidine-2,4-dione (VIII) with N-(2-hydroxyethoxy)phthalimide (VII) by means DEAD gives the adduct (IX), which is treated with hydrazine to eliminate the phthalimido group yielding the substituted hydroxylamine (X). Finally, this compound is condensed with 3-acetyl-6-phenylpyridine (XI) by means of TEA.
| 【1】 Yanagisawa, H.; Fujita, T.; Fujimoto, K.; Yoshioka, T.; Wada, K.; Oguchi, M.; Fujiwara, T.; Horikoshi, H. (Sankyo Co., Ltd.); Oxime derivs., their preparation and their therapeutic use. CA 2159938; EP 0708098; JP 1997048779; US 5703096; US 5780490; US 5972959 . |
| 【2】 Isobe, A.; Fujita, S.; Fujiwara, T.; Yanagisawa, H.; Takamura, M.; Yamada, E.; Hagisawa, Y.; Yachi, M.; Novel oximes having 5-benzyl-2,4-thiazolidinedione as antihyperglycemic agents: Synthesis and structure-activity relationship. Bioorg Med Chem Lett 2000, 10, 4, 373. |
| 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) | 36904 | 1-(6-phenyl-3-pyridinyl)-1-ethanone oxime | C13H12N2O | 详情 | 详情 | |
| (II) | 26934 | 2-bromoethyl tetrahydro-2H-pyran-2-yl ether | C7H13BrO2 | 详情 | 详情 | |
| (III) | 36905 | 1-(6-phenyl-3-pyridinyl)-1-ethanone O-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]oxime | C20H24N2O3 | 详情 | 详情 | |
| (IV) | 36906 | 1-(6-phenyl-3-pyridinyl)-1-ethanone O-(2-hydroxyethyl)oxime | C15H16N2O2 | 详情 | 详情 | |
| (V) | 18803 | 5-(4-hydroxybenzyl)-3-trityl-1,3-thiazolidine-2,4-dione | C29H23NO3S | 详情 | 详情 | |
| (VI) | 36907 | 5-[4-[2-([[(E)-1-(6-phenyl-3-pyridinyl)ethylidene]amino]oxy)ethoxy]benzyl]-3-trityl-1,3-thiazolidine-2,4-dione | C44H37N3O4S | 详情 | 详情 | |
| (VII) | 36908 | 2-(2-hydroxyethoxy)-1H-isoindole-1,3(2H)-dione | C10H9NO4 | 详情 | 详情 | |
| (VIII) | 26462 | 5-(4-hydroxybenzyl)-1,3-thiazolidine-2,4-dione | 74772-78-4 | C10H9NO3S | 详情 | 详情 |
| (IX) | 36909 | 2-(2-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]ethoxy)-1H-isoindole-1,3(2H)-dione | C20H16N2O6S | 详情 | 详情 | |
| (X) | 36910 | 5-[4-[2-(aminooxy)ethoxy]benzyl]-1,3-thiazolidine-2,4-dione | C12H14N2O4S | 详情 | 详情 | |
| (XI) | 36911 | 1-(6-phenyl-3-pyridinyl)-1-ethanone | C13H11NO | 详情 | 详情 |