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【结 构 式】 
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【分子编号】45695 【品名】tert-butyl (4R)-4-[(tert-butylamino)carbonyl]-5,5-dimethyl-1,3-thiazolidine-3-carboxylate 【CA登记号】 |
【 分 子 式 】C15H28N2O3S 【 分 子 量 】316.465 【元素组成】C 56.93% H 8.92% N 8.85% O 15.17% S 10.13% |
合成路线1
该中间体在本合成路线中的序号：(III)Coupling of carboxylic acid (I) with tert-butylamine (II) by means of EDC-HOBt in CH2Cl2 affords carboxamide (III), whose Boc group is removed by treatment with HCl/dioxane to provide compound (IV). Coupling of thiazolidine (IV) to Boc-protected allophenylnorstatine (V) by means of DCC and HOBt in EtOAc provides derivative (VI), whose is deprotected by treatment with HCl/dioxane to yield (VII), which is then coupled to Boc-Val-OH (VIII) with EDC-HOBt in DMF to furnish compound (IX). On the other hand, aminophenol derivative (XI) is condensed with benzyl chloroacetate (XII) in DMF in the presence of K2CO3 to furnish derivative (XIII), which is then debenzylated by hydrogenation over Pd/C in MeOH to yield acetic acid derivative (XIV). Finally, the Boc group of (IX) is removed with HCl/dioxane and the resulting amine (X) is coupled to carboxylic acid (XIV) by first treatment with N-hydroxy-5-norbornene-2,3-dicarboximide (HONB) and DCC in CH2Cl2 followed by treatment with Et3N in DMF. Alternatively, the coupling can be performed by means of EDC and HOBt in DMF.
| 【1】 Takaku, H.; Hattori, N.; Mimoto, T.; et al.; Structure-activity relationship of orally potent tripeptide-based HIV protease inhibitors containing hydroxymethylcarbonyl isostere. Chem Pharm Bull 2000, 48, 9, 1310. |
| 【2】 Terashima, K.; Mimoto, T.; Takaku, H.; Nojima, S.; Kiso, Y. (Japan Energy Corp.); Novel tripeptide cpds. and anti-AIDS drugs. EP 0900566; WO 9829118 . |
| 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) | 34777 | (4R)-3-(tert-butoxycarbonyl)-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid | C11H19NO4S | 详情 | 详情 | |
| (II) | 17895 | 2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine | 75-64-9 | C4H11N | 详情 | 详情 |
| (III) | 45695 | tert-butyl (4R)-4-[(tert-butylamino)carbonyl]-5,5-dimethyl-1,3-thiazolidine-3-carboxylate | C15H28N2O3S | 详情 | 详情 | |
| (IV) | 15836 | N-t-BOC-(2R,3R)-3-Amino-2-hydroxy-4-phenylbutyric acid; (2S,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyric acid | 116661-86-0 | C15H21NO5 | 详情 | 详情 |
| (V) | 45697 | tert-butyl (1S,2S)-1-benzyl-3-[(4R)-4-[(tert-butylamino)carbonyl]-5,5-dimethyl-1,3-thiazolidin-3-yl]-2-hydroxy-3-oxopropylcarbamate | C25H39N3O5S | 详情 | 详情 | |
| (VI) | 45698 | tert-butyl (1S)-1-[[((1S,2S)-1-benzyl-3-[(4R)-4-[(tert-butylamino)carbonyl]-5,5-dimethyl-1,3-thiazolidin-3-yl]-2-hydroxy-3-oxopropyl)amino]carbonyl]-2-methylpropylcarbamate | 1638-63-7 | C30H48N4O6S | 详情 | 详情 |
| (VII) | 29294 | (4R)-3-[(2S,3S)-3-amino-2-hydroxy-4-phenylbutanoyl]-N-(tert-butyl)-5,5-dimethyl-1,3-thiazolidine-4-carboxamide | C20H31N3O3S | 详情 | 详情 | |
| (VIII) | 19733 | (2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid | C10H19NO4 | 详情 | 详情 | |
| (IX) | 45698 | tert-butyl (1S)-1-[[((1S,2S)-1-benzyl-3-[(4R)-4-[(tert-butylamino)carbonyl]-5,5-dimethyl-1,3-thiazolidin-3-yl]-2-hydroxy-3-oxopropyl)amino]carbonyl]-2-methylpropylcarbamate | 1638-63-7 | C30H48N4O6S | 详情 | 详情 |
| (X) | 45699 | (4R)-3-((2S,3S)-3-[[(2S)-2-amino-3-methylbutanoyl]amino]-2-hydroxy-4-phenylbutanoyl)-N-(tert-butyl)-5,5-dimethyl-1,3-thiazolidine-4-carboxamide | C25H40N4O4S | 详情 | 详情 | |
| (XI) | 45700 | N,N-Dimethyl-3-aminophenol; 3-Dimethylaminophenol; m-Dimethylaminophenol | 99-07-0 | C8H11NO | 详情 | 详情 |
| (XII) | 45701 | benzyl 2-chloroacetate | 140-18-1 | C9H9ClO2 | 详情 | 详情 |
| (XIII) | 45702 | benzyl 2-[3-(dimethylamino)phenoxy]acetate | C17H19NO3 | 详情 | 详情 | |
| (XIV) | 45703 | 2-[3-(dimethylamino)phenoxy]acetic acid | C10H13NO3 | 详情 | 详情 |