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【结 构 式】 
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【分子编号】25816 【品名】tert-butyl 2-bromo-3-oxo-3-(2-[[2-(trifluoromethyl)anilino]sulfonyl]phenyl)propanoate 【CA登记号】 |
【 分 子 式 】C20H19BrF3NO5S 【 分 子 量 】522.3398096 【元素组成】C 45.99% H 3.67% Br 15.3% F 10.91% N 2.68% O 15.32% S 6.14% |
合成路线1
该中间体在本合成路线中的序号：(VII)Condensation of methyl 2-(chlorosulfonyl)benzoate (I) with 2-(trifluoromethyl)aniline (II) in the presence of DMAP and pyridine yielded sulfonamide (III), which was then cyclized in refluxing xylene to provide the saccharin derivative (IV). Further condensation with tert-butyl acetate (V) using potassium bis(trimethylsilyl)amide as the base afforded ketoester (VI). Then, bromination with NBS in CCl4 gave (VII), which was cyclized to the benzothiazine (VIII) with K2CO3 in DMF. Treatment with trifluoromethanesulfonic anhydride and pyridine in CH2Cl2 furnished the vinyl triflate (IX), and this was then coupled with boronic acid (X) in the presence of Pd(PPh3)4 and K2CO3 to produce (XI). Finally, the tert-butyl ester was cleaved with trifluoroacetic acid in CH2Cl2.
| 【1】 Lee, C.; et al.; Synthetic studies toward a series of endothelin receptor antagonists. 1,1-Dioxo-2,4-diphenyl-2H-1,2-benzothiazine. 216th ACS Natl Meet (Aug. 23-27, Boston) 1998, Abst MEDI 058. |
| 【2】 Berryman, K.A.; Bunker, A.M.; Doherty, A.M.; Edmunds, J.J. (Pfizer Inc.); Benzothiazine dioxides as endothelin antagonists. EP 0811001; JP 1999501013; WO 9626195 . |
| 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) | 25811 | methyl 2-(chlorosulfonyl)benzoate | 26638-43-7 | C8H7ClO4S | 详情 | 详情 |
| (II) | 25812 | 2-(trifluoromethyl)phenylamine; 2-(trifluoromethyl)aniline | 88-17-5 | C7H6F3N | 详情 | 详情 |
| (III) | 25813 | methyl 2-[[2-(trifluoromethyl)anilino]sulfonyl]benzoate | C15H12F3NO4S | 详情 | 详情 | |
| (IV) | 25814 | 2-[2-(trifluoromethyl)phenyl]-1H-1,2-benzisothiazole-1,1,3(2H)-trione | C14H8F3NO3S | 详情 | 详情 | |
| (V) | 15397 | tert-butyl acetate | 540-88-5 | C6H12O2 | 详情 | 详情 |
| (VI) | 25815 | tert-butyl 3-oxo-3-(2-[[2-(trifluoromethyl)anilino]sulfonyl]phenyl)propanoate | C20H20F3NO5S | 详情 | 详情 | |
| (VII) | 25816 | tert-butyl 2-bromo-3-oxo-3-(2-[[2-(trifluoromethyl)anilino]sulfonyl]phenyl)propanoate | C20H19BrF3NO5S | 详情 | 详情 | |
| (VIII) | 25817 | tert-butyl 4-hydroxy-1,1-dioxo-2-[2-(trifluoromethyl)phenyl]-1,2-dihydro-1lambda(6),2-benzothiazine-3-carboxylate | C20H18F3NO5S | 详情 | 详情 | |
| (IX) | 25818 | tert-butyl 1,1-dioxo-2-[2-(trifluoromethyl)phenyl]-4-[[(trifluoromethyl)sulfonyl]oxy]-1,2-dihydro-1lambda(6),2-benzothiazine-3-carboxylate | C21H17F6NO7S2 | 详情 | 详情 | |
| (X) | 25819 | 7-ethyl-1,3-benzodioxol-5-ylboronic acid | C9H11BO4 | 详情 | 详情 | |
| (XI) | 25820 | tert-butyl 4-(7-ethyl-1,3-benzodioxol-5-yl)-1,1-dioxo-2-[2-(trifluoromethyl)phenyl]-1,2-dihydro-1lambda(6),2-benzothiazine-3-carboxylate | C29H26F3NO6S | 详情 | 详情 |