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【结 构 式】 
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【分子编号】28093 【品名】1,3-thiazolidine 【CA登记号】504-78-9 |
【 分 子 式 】C3H7NS 【 分 子 量 】89.16132 【元素组成】C 40.41% H 7.91% N 15.71% S 35.96% |
合成路线1
该中间体在本合成路线中的序号：(II)By reaction of phthalic anhydride (I) with thiazolidine (II) in CH2Cl2.
| 【1】 Mora Camillo C. (Camillo Corvi SpA); Thiazolidine derivatives and their mucolytic compositions and methods. BE 0892516; DE 3215610; FR 2505834; GB 2098215; JP 57162375; US 4477458 . |
| 【2】 Serradell, M.N.; Castaner, R.M.; Castaner, J.; Braga, P.; Nesosteine Sodium. Drugs Fut 1987, 12, 8, 760. |
| 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) | 11900 | 2-Benzofuran-1,3-dione;1,2-Benzenedicarboxylic Anhydride;1,2-BENZENE DICARBOXYLIC ACID ANHYDRIDE;1,2-BENZENEDICARBONIC ACID, ANHYDRIDE;1,3-DIOXOPHTHALAN;1,3-ISOBENZOFURANDIONE;o-phthalic anhydride; Phthalic anhydride | 85-44-9 | C8H4O3 | 详情 | 详情 |
| (II) | 28093 | 1,3-thiazolidine | 504-78-9 | C3H7NS | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)Protection of beta-alanine derivative (I) with di-tert-butyl dicarbonate afforded the tert-butyl carbamate (II). This was condensed with ethyl piperidine-4-acetate (III) using O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyuronium hexafluorophosphate (HATU) and diisopropyl ethylamine to give amide (IV). Subsequent Boc deprotection of (IV) with trifluoroacetic acid provided amine (V), which was coupled with 2-fluoro-4-cyanobenzoic acid (VI) in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 1-hydroxybenzotriazole yielding (VII). Treatment of the resulting cyanobenzamide (VII) with SH2 and Et3N produced the corresponding thioamide, which was S-alkylated with MeI to give (VIII). Finally, displacement of the methylthio group of (VIII) with thiazolidine (IX) furnished the corresponding amidine.
| 【1】 Hayashi, Y.; Harada, T.; Katada, J.; et al.; GPIIb/IIIa integrin antagonists with the new conformational restriction unit, trisubstituted beta-amino acid derivatives, and substituted benzamidine structure. J Med Chem 1998, 41, 12, 2345. |
| 【2】 Hayashi, Y.; Harada, T.; Tachiki, A.; Katada, J. (Nippon Steel Corp.); Fibrinogen receptor antagonists and medicinal preparations containing the same as the active ingredient. EP 0852225; JP 1998017550; WO 9749682 . |
| 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) | 28085 | 3-amino-2,2-dimethylpentanoic acid | C7H15NO2 | 详情 | 详情 | |
| (II) | 28086 | 3-[(tert-butoxycarbonyl)amino]-2,2-dimethylpentanoic acid | C12H23NO4 | 详情 | 详情 | |
| (III) | 28087 | 4-Piperidineacetic acid ethyl ester; ethyl 2-(4-piperidinyl)acetate | C9H17NO2 | 详情 | 详情 | |
| (IV) | 28088 | ethyl 2-(1-[3-[(tert-butoxycarbonyl)amino]-2,2-dimethylpentanoyl]-4-piperidinyl)acetate | C21H38N2O5 | 详情 | 详情 | |
| (V) | 28089 | ethyl 2-[1-(3-amino-2,2-dimethylpentanoyl)-4-piperidinyl]acetate | C16H30N2O3 | 详情 | 详情 | |
| (VI) | 28090 | 4-cyano-2-fluorobenzoic acid | C8H4FNO2 | 详情 | 详情 | |
| (VII) | 28091 | ethyl 2-(1-[3-[(4-cyano-2-fluorobenzoyl)amino]-2,2-dimethylpentanoyl]-4-piperidinyl)acetate | C24H32FN3O4 | 详情 | 详情 | |
| (VIII) | 28092 | ethyl 2-[1-[3-([2-fluoro-4-[imino(methylsulfanyl)methyl]benzoyl]amino)-2,2-dimethylpentanoyl]-4-piperidinyl]acetate | C25H36FN3O4S | 详情 | 详情 | |
| (IX) | 28093 | 1,3-thiazolidine | 504-78-9 | C3H7NS | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)The condensation of N-(tert-butoxycarbonyl)-L-isoleucine (I) with thiazolidine (II) by means of isobutyl chloroformate and N-ethylmorpholine (NEM) in THF gives 3-[N-(tert-butoxycarbonyl)-L-isoleucyl]thiazolidine (III), which is deprotected with HCl and thioanisole in acetic acid.
| 【1】 Sorbera, L.A.; Revel, L.; Castañer, J.; P32/98. Drugs Fut 2001, 26, 9, 859. |
| 【2】 Born, I.; Barth, A.; Ansorge, S.; faust, J.; Neubert, K.; Schön, E.; Steinmetzer, T.; Demuth, H.-U.; Dipeptidyl peptidase IV in the immune system. Effects of specific enzyme inhibitors on activity of dipeptidyl peptidase IV and proliferation of human lymphocytes. Biol Chem Hoppe Seyler 1991, 372, 5, 305. |
| 【3】 Faust, J.; Heins, J.; Rahfeld, J.U.; Demuth, H.-U.; Steinmetzer, T.; Born, I.; Barth, A.; Neubert, K. (Martin Luther Universitat Halle-Wittenberg); Process for the preparation of new dipeptidyl peptidase IV inhibitors. DD 296075 . |