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【结 构 式】 
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【分子编号】26786 【品名】N-[2-[((1S)-1-[[(butylsulfonyl)amino]carbonyl]-2-methylpropyl)amino]-1-[4-(5-isoxazolyl)benzyl]-2-oxoethyl]-N,3,5-trimethylbenzamide 【CA登记号】 |
【 分 子 式 】C31H40N4O6S 【 分 子 量 】596.74796 【元素组成】C 62.4% H 6.76% N 9.39% O 16.09% S 5.37% |
合成路线1
该中间体在本合成路线中的序号：(XX)1-Butanesulfonyl chloride (XII) was reacted with ammonia in acetonitrile, and the resulting sulfonamide (XIII) was then converted to the N-trimethylsilyl derivative (XIV). This compound was coupled with acid fluoride (XVII), (obtained from Boc-valine (XV) and cyanuric fluoride (XVI)), to provide Boc-valinesulfonamide (XVIII). The Boc group of (XVIII) was then removed by acid treatment to give (XIX). Coupling of this chiral intermediate (XIX) with racemic acid (XI) in a biphasic solvent system, with partial isomerization of acid (XI), furnished the amide (XX) as a 12:1 diastereomeric mixture. The major D,L diastereoisomer was then isolated either by preparative HPLC or by recrystallization from isopropanol.
| 【1】 Sakaki, J.; Murata, T.; Yuumoto, Y.; Nakamura, I.; Hayakawa, K.; Stereoselective synthesis of a novel and bifunctional endothelin antagonist, IRL 3630. Bioorg Med Chem Lett 1998, 8, 16, 2247. |
| 【2】 Sakaki, J.; Murata, T.; Yuumoto, Y.; Nakamura, I.; Okada, T. (Novartis Japan KK); Antagonists of endothelin receptors. JP 1999512702; WO 9711960 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 26778 | N-(3,5-dimethylbenzoyl)-4-(5-isoxazolyl)-N-methylphenylalanine | C22H22N2O4 | 详情 | 详情 | |
| (XII) | 26779 | 1-butanesulfonyl chloride | 2386-60-9 | C4H9ClO2S | 详情 | 详情 |
| (XIII) | 26780 | 1-butanesulfonamide | C4H11NO2S | 详情 | 详情 | |
| (XIV) | 26781 | N-(trimethylsilyl)-1-butanesulfonamide | C7H19NO2SSi | 详情 | 详情 | |
| (XV) | 19733 | (2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid | C10H19NO4 | 详情 | 详情 | |
| (XVI) | 26782 | Cyanuric fluoride; 2,4,6-trifluoro-1,3,5-triazine | 675-14-9 | C3F3N3 | 详情 | 详情 |
| (XVII) | 26783 | tert-butyl (1S)-1-(fluorocarbonyl)-2-methylpropylcarbamate | C10H18FNO3 | 详情 | 详情 | |
| (XVIII) | 26784 | tert-butyl (1S)-1-[[(butylsulfonyl)amino]carbonyl]-2-methylpropylcarbamate | C14H28N2O5S | 详情 | 详情 | |
| (XIX) | 26785 | N-[(2S)-2-amino-3-methylbutanoyl]-1-butanesulfonamide | C9H20N2O3S | 详情 | 详情 | |
| (XX) | 26786 | N-[2-[((1S)-1-[[(butylsulfonyl)amino]carbonyl]-2-methylpropyl)amino]-1-[4-(5-isoxazolyl)benzyl]-2-oxoethyl]-N,3,5-trimethylbenzamide | C31H40N4O6S | 详情 | 详情 |