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【结 构 式】 
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【分子编号】53613 【品名】(2S,4S)-4-(acetylsulfanyl)-1-methyl-2-pyrrolidinecarboxylic 1,1-dimethylpropanoic anhydride 【CA登记号】n/a |
【 分 子 式 】C13H21NO4S 【 分 子 量 】287.38008 【元素组成】C 54.33% H 7.37% N 4.87% O 22.27% S 11.16% |
合成路线1
该中间体在本合成路线中的序号：(XII)The reaction of the hydroxyproline 4-methoxybenzyl ester (VIII) with Ms-Cl and DIEA in THF gives the mesylate (IX), which is treated with thioacetic acid and Cs2CO3 in DMA to yield the acetylsulfanyl derivative (X). The Boc deprotection of (X) with 4N HCl in ethyl acetate, followed by methylation with HCHO/HCOOH and simultaneous ester hydrolysis, affords the methylated proline (XI), which is activated with pivaloyl chloride and DIEA in acetonitrile to the mixed anhydride (XII). The condensation of (XII) with the intermediate pyrrolidine (VII) by means of DIEA in acetonitrile provides the adduct (XIII), which is further condensed with the carbapenem (XIV) by means of NaOMe in methanol to give the intermediate (XV). Finally, this compound is deprotected by hydrogenation with H2 over Pd/C in THF/water to furnish the target 1-beta-methyl carbapenem.
| 【1】 Kanno, O.; Shibayama, T.; Ohya, S.; Shimoji, Y.; Kuwahara, S.; Ishikawa, K.; Kojima, K.; Kawamoto, I.; R-115685, a novel parenteral carbapenem: Synthesis and structure-activity relationships. 40th Intersci Conf Antimicrob Agents Chemother (Sept 17 2000, Toronto) 2000, Abst F-1229. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 53608 | 2-({imino[(4-nitrobenzoyl)amino]methyl}amino)-N-[(3S)pyrrolidinyl]acetamide | n/a | C14H18N6O4 | 详情 | 详情 |
| (VIII) | 53609 | 1-(tert-butyl) 2-(4-methoxybenzyl) (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate | n/a | C18H25NO6 | 详情 | 详情 |
| (IX) | 53610 | 1-(tert-butyl) 2-(4-methoxybenzyl) (2S,4R)-4-[(methylsulfonyl)oxy]-1,2-pyrrolidinedicarboxylate | n/a | C19H27NO8S | 详情 | 详情 |
| (X) | 53611 | 1-(tert-butyl) 2-(4-methoxybenzyl) (2S,4S)-4-(acetylsulfanyl)-1,2-pyrrolidinedicarboxylate | n/a | C20H27NO6S | 详情 | 详情 |
| (XI) | 53612 | (2S,4S)-4-(acetylsulfanyl)-1-methyl-2-pyrrolidinecarboxylic acid | n/a | C8H13NO3S | 详情 | 详情 |
| (XII) | 53613 | (2S,4S)-4-(acetylsulfanyl)-1-methyl-2-pyrrolidinecarboxylic 1,1-dimethylpropanoic anhydride | n/a | C13H21NO4S | 详情 | 详情 |
| (XIII) | 13224 | 4-nitrobenzyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | 90776-59-3 | C29H27N2O10P | 详情 | 详情 |
| (XIV) | 53614 | S-{(3S,5S)-5-[((3S)-3-{[2-({imino[(4-nitrobenzoyl)amino]methyl}amino)acetyl]amino}pyrrolidinyl)carbonyl]-1-methylpyrrolidinyl} ethanethioate | n/a | C22H29N7O6S | 详情 | 详情 |
| (XV) | 53615 | 4-nitrobenzyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-3-({(3S,5S)-5-[((3S)-3-{[2-({imino[(4-nitrobenzoyl)amino]methyl}amino)acetyl]amino}pyrrolidinyl)carbonyl]-1-methylpyrrolidinyl}sulfanyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | n/a | C37H43N9O11S | 详情 | 详情 |