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【结 构 式】

【分子编号】29573

【品名】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

【CA登记号】

【 分 子 式 】C13H15NO6S

【 分 子 量 】313.33124

【元素组成】C 49.83% H 4.83% N 4.47% O 30.64% S 10.23%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(VII)

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
Extended Information