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【结 构 式】 
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【分子编号】29569 【品名】methyl (2S)-2-[[(benzyloxy)carbonyl]amino]-3-(3,4-dihydroxyphenyl)propanoate 【CA登记号】 |
【 分 子 式 】C18H19NO6 【 分 子 量 】345.352 【元素组成】C 62.6% H 5.55% N 4.06% O 27.8% |
合成路线1
该中间体在本合成路线中的序号：(III)L-DOPA (I) was esterified by means of MeOH and SOCl2, and the resulting aminoester (II) was protected with benzyloxycarbonyloxy succinimide to give carbamate (III). Further reaction of (III) with 1,2-dibromoethane produced the cyclic diether derivative (IV). Chlorsulfonylation of (IV), followed by basic treatment with DMAP and Et3N gave rise to the benzothiazine (V). After N-alkylation of (V) with iodoethane and K2CO3, basic hydrolysis of the resulting methyl ester (VI) provided carboxylic acid (VII). This was coupled to L-phenylalaninol (VIII) using benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and 1-hydroxybenzotriazole (HOBt) to afford the corresponding amide as a diastereomeric mixture, which was separated by flash chromatography. The required (S,S)-diastereoisomer (IX) was then oxidized to the title aldehyde using Dess-Martin periodinane reagent.
| 【1】 Wells, G.J.; et al.; 1,2-Benzothiazine 1,1-dioxide P2-P3 peptide mimetic aldehyde calpain I inhibitors. J Med Chem 2001, 44, 21, 3488. |
| 【2】 Bihovsky, R.; Wells, G.J.; Tao, M. (Cephalon, Inc.); Benzothiazo and related heterocyclic group-containing cysteine and serine protease. WO 9821186 . |
| 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) | 15272 | (2S)-2-amino-3-(3,4-dihydroxyphenyl)propionic acid; 3-hydroxy-L-tyrosine; Levodopa | 59-92-7 | C9H11NO4 | 详情 | 详情 |
| (II) | 29568 | methyl (2S)-2-amino-3-(3,4-dihydroxyphenyl)propanoate | C10H13NO4 | 详情 | 详情 | |
| (III) | 29569 | methyl (2S)-2-[[(benzyloxy)carbonyl]amino]-3-(3,4-dihydroxyphenyl)propanoate | C18H19NO6 | 详情 | 详情 | |
| (IV) | 29570 | methyl (2S)-2-[[(benzyloxy)carbonyl]amino]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)propanoate | C20H21NO6 | 详情 | 详情 | |
| (V) | 29571 | methyl 1,1-dioxo-1,2,3,4,7,8-hexahydro-2H-[1,4]dioxino[2,3-g][1,2]benzothiazine-3-carboxylate | C12H13NO6S | 详情 | 详情 | |
| (VI) | 29572 | methyl 2-ethyl-1,1-dioxo-1,2,3,4,7,8-hexahydro-2H-[1,4]dioxino[2,3-g][1,2]benzothiazine-3-carboxylate | C14H17NO6S | 详情 | 详情 | |
| (VII) | 29573 | 2-ethyl-1,1-dioxo-1,2,3,4,7,8-hexahydro-2H-[1,4]dioxino[2,3-g][1,2]benzothiazine-3-carboxylic acid | C13H15NO6S | 详情 | 详情 | |
| (VIII) | 28523 | (2S)-2-amino-3-phenyl-1-propanol; L-phenylalanilol; (S)-2-amino-3-phenyl-1-propanol | 5267-64-1 | C9H13NO | 详情 | 详情 |
| (IX) | 29574 | (3S)-N-[(1S)-1-benzyl-2-hydroxyethyl]-2-ethyl-1,1-dioxo-1,2,3,4,7,8-hexahydro-2H-[1,4]dioxino[2,3-g][1,2]benzothiazine-3-carboxamide | C22H26N2O6S | 详情 | 详情 | |
| (X) | 18845 | Dess-Martin periodinane; 1,1,1-Triacetoxy-1,2-benziodoxol-3(1H)-one | 87413-09-0 | C13H13IO8 | 详情 | 详情 |