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【结 构 式】 
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【分子编号】68520 【品名】(R)-2-(2-((3,3-dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-8-yl)oxy)acetamido)-2-phenylacetic acid 【CA登记号】 |
【 分 子 式 】C34H42N2O6S2 【 分 子 量 】638.849 【元素组成】C 663.92% H 6.63% N 4.38% O 15.03% S 10.04% |
合成路线1
该中间体在本合成路线中的序号：(VII)Condensation of the 1,5-benzothiazepin-8-ol derivative (I) with ethyl bromoacetate (II) in the presence of Bu4NBr and Na2CO3 in refluxing acetonitrile yields ethyl ester (III), which is then hydrolyzed with NaOH in EtOH to give the corresponding acid (IV). Subsequent coupling of carboxylic acid (IV) with (R)-2-phenylglycine methyl ester hydrochloride (V) using TBTU and DIEA in CH2Cl2 followed by hydrolysis of the resultant methyl ester (VI) with NaOH in MeOH produces the N-acyl amino acid (VII). After coupling of acid (VII) with tert-butyl glycinate (VIII), using the same procedure as above, the resulting tert-butyl ester (IX) is finally cleaved using TFA in CH2Cl2 .
| 【1】 Starke, I., Blomberg, D., Dahlstrom, M. (AstraZeneca AB; AstraZeneca plc). Chemical compounds. EP 1345918, JP 2004196815, JP 2004516285, US 2004067933, US 7192945, WO 2002050051. |
| 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) | 68515 | 3,3-dibutyl-8-hydroxy-7-(methylthio)-5-phenyl-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine 1,1-dioxide | C24H33NO3S2 | 详情 | 详情 | |
| (II) | 16640 | Ethyl 2-bromoacetate; Ethyl bromoacetate | 105-36-2 | C4H7BrO2 | 详情 | 详情 |
| (III) | 68516 | ethyl 2-((3,3-dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-8-yl)oxy)acetate | C28H39NO5S2 | 详情 | 详情 | |
| (IV) | 68517 | 2-((3,3-dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-8-yl)oxy)acetic acid | C26H35NO5S2 | 详情 | 详情 | |
| (V) | 68518 | (R)-2-phenylglycine methyl ester hydrochloride | C9H11NO2.HCl | 详情 | 详情 | |
| (VI) | 68519 | (R)-methyl 2-(2-((3,3-dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-8-yl)oxy)acetamido)-2-phenylacetate | C35H44N2O6S2 | 详情 | 详情 | |
| (VII) | 68520 | (R)-2-(2-((3,3-dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-8-yl)oxy)acetamido)-2-phenylacetic acid | C34H42N2O6S2 | 详情 | 详情 | |
| (VIII) | 27841 | tert-butyl 2-aminoacetate;tert-butyl glycinate;Glycine tert-butyl ester | 6456-74-2 | C6H13NO2 | 详情 | 详情 |
| (IX) | 68521 | (R)-tert-butyl 2-(2-(2-((3,3-dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-8-yl)oxy)acetamido)-2-phenylacetamido)acetate | C40H53N3O7S2 | 详情 | 详情 |