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【结 构 式】 
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【分子编号】28853 【品名】(2R)-3-(acetylsulfanyl)-2-methylpropionic acid;(R)-3-(acetylthio)-2-methylpropanoic acid 【CA登记号】74431-52-0 |
【 分 子 式 】C6H10O3S 【 分 子 量 】162.2096 【元素组成】C 44.43% H 6.21% O 29.59% S 19.77% |
合成路线1
该中间体在本合成路线中的序号：(V)The reaction of cyclopentylamine (I) with tertbutyl bromoacetate (II) by means of NH3 in acetonitrile gives N-cyclopentylglycine tert-butyl ester (III), which is condensed with 3-(acetylthio)-2-methylpropionyl chloride (IV) [prepared from the corresponding acid (V) with SOCl2] by means of triethylamine in dioxane to yield the acylated glycine (VI). Deacetylation of (VI) with dry ammonia in methanol affords the mercapto derivative (VII), which is acylated with pivaloyl chloride (VIII) in the usual way giving the corresponding thio ester (IX). Finally, this compound is hydrolyzed partially with trimethylsilyl iodide in methylene chloride.
| 【1】 Suh, J.T.; et al.; Angiotensin-converting enzyme inhibitors. New orraly active antihypertensive (mercaptoalkanoyl)- and [(acylthio)alkanoyl]glycine derivatives. J Med Chem 1985, 28, 1, 57-66. |
| 【2】 Castaner, J.; Serradell, M.N.; Pivopril. Drugs Fut 1986, 11, 2, 116. |
| 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) | 28850 | cyclopentanamine | 1003-03-8 | C5H11N | 详情 | 详情 |
| (II) | 17430 | 2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate | 5292-43-3 | C6H11BrO2 | 详情 | 详情 |
| (III) | 28851 | tert-butyl 2-(cyclopentylamino)acetate | C11H21NO2 | 详情 | 详情 | |
| (IV) | 28852 | (2R)-3-Acetylthio-2-methylpropionyl chloride;L-3-(Acetylthio)-2-methylpropanoyl chloride ;S-[(2R)-3-chloro-2-methyl-3-oxopropyl] ethanethioate | 74345-73-6 | C6H9ClO2S | 详情 | 详情 |
| (V) | 28853 | (2R)-3-(acetylsulfanyl)-2-methylpropionic acid;(R)-3-(acetylthio)-2-methylpropanoic acid | 74431-52-0 | C6H10O3S | 详情 | 详情 |
| (VI) | 28854 | tert-butyl 2-[[(2S)-3-(acetylsulfanyl)-2-methylpropanoyl](cyclopentyl)amino]acetate | C17H29NO4S | 详情 | 详情 | |
| (VII) | 28855 | tert-butyl 2-[cyclopentyl[(2S)-2-methyl-3-sulfanylpropanoyl]amino]acetate | C15H27NO3S | 详情 | 详情 | |
| (VIII) | 13597 | 2,2-Dimethylpropanoyl chloride; Pivaloyl chloride | 3282-30-2 | C5H9ClO | 详情 | 详情 |
| (IX) | 28856 | tert-butyl 2-(cyclopentyl[(2S)-3-[(2,2-dimethylpropanoyl)sulfanyl]-2-methylpropanoyl]amino)acetate | C20H35NO4S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)
| 【1】 Shimazaki M,Hasegawa J,Kan K.Synthesis of captopril starting from potically active β-hydroxy acid.Chem Pharm Bull,1982,30:3139. |
| 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) | 69585 | (R)-3-chloro-2-methylpropanoyl chloride | C4H6Cl2O | 详情 | 详情 | |
| (II) | 69586 | (R)-3-chloro-2-methylpropanoic acid | C4H7ClO2 | 详情 | 详情 | |
| (III) | 69587 | (R)-3-mercapto-2-methylpropanoic acid | C4H8O2S | 详情 | 详情 | |
| (IV) | 28853 | (2R)-3-(acetylsulfanyl)-2-methylpropionic acid;(R)-3-(acetylthio)-2-methylpropanoic acid | 74431-52-0 | C6H10O3S | 详情 | 详情 |
| (V) | 16731 | L-proline | 147-85-3 | C5H9NO2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)
| 【1】 Rudio Zurita P.N-[(2S)(-)-3-Mercapto-2-methylpropanoyl]-L-proline:ES,Patent 493,743,1980. |
| 【2】 Kim DK.Process for the preparation of pyrrolidine derivatives:DE,Patent 3,526,023,1986. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 69590 | (S)-trimethylsilyl pyrrolidine-2-carboxylate | C8H17NO2Si | 详情 | 详情 | |
| (I) | 28853 | (2R)-3-(acetylsulfanyl)-2-methylpropionic acid;(R)-3-(acetylthio)-2-methylpropanoic acid | 74431-52-0 | C6H10O3S | 详情 | 详情 |
| (II) | 69589 | (S)-3-(acetylthio)-2-methylpropanoic acid | C11H18O4S | 详情 | 详情 | |
| (IV) | 69591 | (S)-trimethylsilyl 1-((S)-3-(acetylthio)-2-methylpropanoyl)pyrrolidine-2-carboxylate | C14H25NO4SSi | 详情 | 详情 |