【结 构 式】 |
【分子编号】26784 【品名】tert-butyl (1S)-1-[[(butylsulfonyl)amino]carbonyl]-2-methylpropylcarbamate 【CA登记号】 |
【 分 子 式 】C14H28N2O5S 【 分 子 量 】336.4528 【元素组成】C 49.98% H 8.39% N 8.33% O 23.78% S 9.53% |
合成路线1
该中间体在本合成路线中的序号:(XVIII)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 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). Finally, coupling of this chiral intermediate with the previously obtained racemic acid (XI) furnished the title compound as a 7:3 mixture of diastereoisomers.
【1】 Sakaki, J.; Murata, T.; Yuumoto, Y.; Nakamura, I.; Frueh, T.; Pitterna, T.; Iwasaki, G.; Oda, K.; Yamamura, T.; Hayakawa, K.; Discovery of IRL 3461: A novel and potent endothelin antagonist with balanced ETA/ETB affinity. Bioorg Med Chem Lett 1998, 8, 16, 2241. |
【2】 Fruh, T.; Pitterna, T.; Murata, T.; Svensson, L.D.; Yuumoto, Y.; Sakaki, J. (Novartis Japan KK); Antagonists of endothelin receptors. EP 0753004; JP 1997510720; US 5703106; WO 9526360 . |
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 |
合成路线2
该中间体在本合成路线中的序号:(XVIII)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 |