5-(4-hydroxybenzyl)-1,3-thiazolidine-2,4-dione -Drug Synthesis Database

【结构式】

【分子编号】26462

【品名】5-(4-hydroxybenzyl)-1,3-thiazolidine-2,4-dione

【CA登记号】74772-78-4

【分子式】C₁₀H₉NO₃S

【分子量】223.2524

【元素组成】C 53.8% H 4.06% N 6.27% O 21.5% S 14.36%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(VIII)

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.

参考文献中间体

合成目标

【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：(VIII)

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.

参考文献中间体

合成目标

【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

合成路线3

该中间体在本合成路线中的序号：(XII)

The condensation of the chloromethylamino intermediate (IV) with 5-(4-hydroxybenzyl)thiazolidine-2,4-dione (XII) by means of NaH in in hot DMF gives the previously reported intermediate (XI), which is finally deprotected with HCl in acetic acid as before.

参考文献中间体

合成目标

【1】 Casturi, S.R.; Lohray, V.B.; Kallam, A.R.; Pingali, H.; Ramanujam, R.; Alla, S.R. (Dr. Reddy's Research Foundation); Cpds. having antidiabetic, hypolipidemic, antihypertensive properties, process for their preparation and pharmaceutical compsns. containing them. US 5925656 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	26457	N-[[5-(benzyloxy)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-yl]methyl]-2-chloro-N-methyl-1-ethanamine		C₂₄H₃₂ClNO₂	详情	详情
(XI)	26461	5-(4-[2-[[[5-(benzyloxy)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-yl]methyl](methyl)amino]ethoxy]benzyl)-1,3-thiazolidine-2,4-dione		C₃₄H₄₀N₂O₅S	详情	详情
(XII)	26462	5-(4-hydroxybenzyl)-1,3-thiazolidine-2,4-dione	74772-78-4	C₁₀H₉NO₃S	详情	详情

Extended Information