-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】(Z)-5-[4-[2-[N-(6-Hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-1-benzopyran-2-ylmethyl)-N-methylamino]-ethoxy]benzylidene]-2,4-thiazolidinedione

【CA登记号】

【分子式】C₂₇H₃₂N₂O₅S

【分子量】496.63049

【开发单位】Dr. Reddy′s Res. Found., Hyderabad (IN)

【药理作用】ENDOCRINE DRUGS, ANTIDIABETIC DRUGS

合成路线1 合成路线2

合成路线1

Treatment of chromane (I) with metanesulfonyl chloride in pyridine at 0 C afforded mesylate (II), which was treated with 2-methylaminoethanol (III) to afford tertiary amine (IV). Reaction with SOCl2 gave chloride (V), and further reaction with p-hydroxybenzaldehyde (VI) provided (VII). Aldehyde (VII) was then condensed with 2,4-thiazolidinedione (VIII) in the presence of piperidine benzoate in toluene to furnish (IX). Finally, the benzyl protecting group was removed by treatment with acetic acid-hydrochloric acid at 60 C to give the title compound.

参考文献中间体

【1】 Reddy, K.A.; Lohray, B.B.; Bhushan, V.; Reddy, A.S.; Kishore, P.H.; Rao, VV.; Saibaba, V.; Bajji, A.C.; Rajesh, B.M.; Reddy, K.V.; Chakrabarti, R.; Rajagopalan, R.; Novel euglycemic and hypolipidemic agents: Part-2. Antioxidant moiety as structural motif. Bioorg Med Chem Lett 1998, 8, 9, 999-1002.

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)	18084	[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methanol		C₂₁H₂₆O₃	详情	详情
(II)	18085	[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl methanesulfonate		C₂₂H₂₈O₅S	详情	详情
(III)	13324	2-Methylaminoethanol; 2-(Methylamino)-1-ethanol	109-83-1	C₃H₉NO	详情	详情
(IV)	18086	2-[[[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl](methyl)amino]-1-ethanol		C₂₄H₃₃NO₃	详情	详情
(V)	18087	N-[[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl]-N-(2-chloroethyl)-N-methylamine; N-[[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl]-2-chloro-N-methyl-1-ethanamine		C₂₄H₃₂ClNO₂	详情	详情
(VI)	13433	4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde	123-08-0	C₇H₆O₂	详情	详情
(VII)	18088	4-[2-[[[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl](methyl)amino]ethoxy]benzaldehyde		C₃₁H₃₇NO₄	详情	详情
(VIII)	10883	1,3-Thiazolane-2,4-dione; 2,4-Thiazolidinedione	2295-31-0	C₃H₃NO₂S	详情	详情
(IX)	18089	5-[(Z)-(4-[2-[[[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl](methyl)amino]ethoxy]phenyl)methylidene]-1,3-thiazolidine-2,4-dione		C₃₄H₃₈N₂O₅S	详情	详情

合成路线2

A new synthesis of the title compound, very similar to that already published, is reported: The condensation of 6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-1-benzopyran-2-ylmethyl methanesulfonate (I) with 2-(methylamino)ethanol (II) by heating at 120 C gives the tertiary amine (III), which is condensed with 4-fluorobenzaldehyde (IV) by means of NaH in DMF yielding the 4-alkoxy benzaldehyde (V). A new condensation of (V) with thiazolidine-2,4-dione (VI) by means of piperidine in refluxing toluene affords the benzyloxy derivative of the target compound (VII). Finally, the target compound is obtained by treatment of (VII) with HCl in acetic acid.

参考文献中间体

【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
(I)	26454	6-(benzyloxy)-2,5,7,8-tetramethyl-2-([[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]methyl)chromane		C₂₄H₃₂O₃S	详情	详情
(II)	13324	2-Methylaminoethanol; 2-(Methylamino)-1-ethanol	109-83-1	C₃H₉NO	详情	详情
(III)	18086	2-[[[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl](methyl)amino]-1-ethanol		C₂₄H₃₃NO₃	详情	详情
(IV)	12337	4-fluorobenzaldehyde	459-57-4	C₇H₅FO	详情	详情
(V)	18088	4-[2-[[[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl](methyl)amino]ethoxy]benzaldehyde		C₃₁H₃₇NO₄	详情	详情
(VI)	10883	1,3-Thiazolane-2,4-dione; 2,4-Thiazolidinedione	2295-31-0	C₃H₃NO₂S	详情	详情
(VII)	18089	5-[(Z)-(4-[2-[[[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl](methyl)amino]ethoxy]phenyl)methylidene]-1,3-thiazolidine-2,4-dione		C₃₄H₃₈N₂O₅S	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)