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【结 构 式】 
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【药物名称】 【化学名称】(Z)-5-[4-[1-(6-Benzyloxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-1-benzopyran-2-ylmethyl)pyrrolidin-2(S)-ylmethoxy]benzylidene]thiazolidine-2,4-dione maleate 【CA登记号】199108-11-7, 199108-10-6 (free base), 199108-13-9 (HCl), 199108-12-8 (sodium salt) 【 分 子 式 】C40H44N2O9S 【 分 子 量 】728.86868 |
【开发单位】Dr. Reddy's Research Foundation (Originator) 【药理作用】Antidiabetic Drugs, ENDOCRINE DRUGS, Insulin Sensitizers |
合成路线1
Mesylate (I) is heated with L-prolinol (II) to furnish pyrrolidine derivative (III), which can be converted into (VII) by different ways: 1) Treatment of (III) with t-BuOK and reaction with 4-fluorobenzaldehyde (IV) in DMF. 2) Conversion of (III) into chloropiperidine derivative (V) by means of SOCl2 in benzene, followed by reaction with 4-hydroxyaldehyde (VI) and K2CO3 in DMF in and chromatographic separation. 3) Mitsunobu reaction between (III) and 4-hydroxyaldehyde (VI) by treatment with PPh3 and DEAD in THF, followed by chromatographic separation. Derivative (VII) is condensed with 2,4-thiazolidinedione (VIII) in toluene in the presence of piperidine and benzoic acid to afford (IX), which is finally converted into its maleate form by treatment with maleic acid in Et2O.
| 【1】 Lohray, B.B.; Anji Reddy, K.; Bhushan, V.; et al.; Novel antidiabetic and hypolipidemic agents. 5. Hydroxyl versus benzyloxy containing chroman derivatives. J Med Chem 1999, 42, 17, 3265. |
| 【2】 Alla, S.R.; Ramanujam, R.; Bajji, A.C.; Lohray, B.B.; Lohray, V.B.; Chakrabarti, R. (Dr. Reddy's Research Foundation; Reddy-Cheminor Inc.); Novel heterocyclic cpds. having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compsns. containing them. WO 9741121 . |
| 【3】 Ramanujam, R.; Chakrabarti, R.; Lohray, B.B.; Bajji, A.C.; Lohray, V.B.; Alla, S.R. (Dr. Reddy's Research Foundation); Heterocyclic cpds. having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compsns. containing them. US 5889032 . |
| 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) | 21347 | (2S)pyrrolidinylmethanol | 23356-96-9 | C5H11NO | 详情 | 详情 |
| (III) | 42275 | ((2S)-1-[[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl]pyrrolidinyl)methanol | C26H35NO3 | 详情 | 详情 | |
| (IV) | 12337 | 4-fluorobenzaldehyde | 459-57-4 | C7H5FO | 详情 | 详情 |
| (V) | 42276 | (3R)-1-[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]-3-chloropiperidine; benzyl 2-[(3R)-3-chloropiperidinyl]-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-6-yl ether | C25H32ClNO2 | 详情 | 详情 | |
| (VI) | 13433 | 4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde | 123-08-0 | C7H6O2 | 详情 | 详情 |
| (VII) | 42277 | 4-[((2S)-1-[[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl]pyrrolidinyl)methoxy]benzaldehyde | C33H39NO4 | 详情 | 详情 | |
| (VIII) | 10883 | 1,3-Thiazolane-2,4-dione; 2,4-Thiazolidinedione | 2295-31-0 | C3H3NO2S | 详情 | 详情 |
| (IX) | 42278 | 5-((Z)-[4-[((2S)-1-[[6-(benzyloxy)-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methyl]pyrrolidinyl)methoxy]phenyl]methylidene)-1,3-thiazolidine-2,4-dione | C36H40N2O5S | 详情 | 详情 |