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【结 构 式】 
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【分子编号】18596 【品名】N-[2,4-dichloro-3-(hydroxymethyl)phenyl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-methylacetamide 【CA登记号】 |
【 分 子 式 】C18H14Cl2N2O4 【 分 子 量 】393.22564 【元素组成】C 54.98% H 3.59% Cl 18.03% N 7.12% O 16.28% |
合成路线1
该中间体在本合成路线中的序号：(VII)Protection of 2,4-dichloro-3-nitrobenzyl alcohol (I) with tert-butyldiphenylsilyl chloride (TBDPSCl) in the presence of imidazole in DMF provided silyl ether (II). Then, reduction of the nitro group with hydrazine, FeCl3, and carbon gave aniline (III), which was condensed with N-phthaloylglycyl chloride (IV) to afford glycinamide (V). Alkylation with iodomethane in the presence of NaH yielded N-methylaniline (VI) and, then, the silyl ether was deprotected with tetra-n-butylammonium fluoride to produce alcohol (VII). Treatment with methanesulfonyl chloride provided mesylate (VIII), which was coupled with quinolinol (IX) in the presence of NaH in DMF to give ether (X). Subsequent removal of the N-phthaloyl group with hydrazine hydrate yielded amine (XI).
| 【1】 Abe, Y.; Kayakiri, H.; Satoh, S.; Inoue, T.; Sawada, Y.; Inamura, N.; Asano, M.; Aramori, I.; Hatori, C.; Sawai, H.; Oku, T.; Tanaka, H.; A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 3. Discovering bioisosteres of the imidazo[1,2-a]pyridine moiety. J Med Chem 1998, 41, 21, 4062. |
| 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) | 18590 | (2,6-dichloro-3-nitrophenyl)methanol | C7H5Cl2NO3 | 详情 | 详情 | |
| (II) | 18591 | tert-butyl[(2,6-dichloro-3-nitrobenzyl)oxy]diphenylsilane; tert-butyl(diphenyl)silyl 2,6-dichloro-3-nitrobenzyl ether | C23H23Cl2NO3Si | 详情 | 详情 | |
| (III) | 18592 | 3-([[tert-butyl(diphenyl)silyl]oxy]methyl)-2,4-dichlorophenylamine; 3-([[tert-butyl(diphenyl)silyl]oxy]methyl)-2,4-dichloroaniline | C23H25Cl2NOSi | 详情 | 详情 | |
| (IV) | 10278 | 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | 6780-38-7 | C10H6ClNO3 | 详情 | 详情 |
| (V) | 18594 | N-[3-([[tert-butyl(diphenyl)silyl]oxy]methyl)-2,4-dichlorophenyl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetamide | C33H30Cl2N2O4Si | 详情 | 详情 | |
| (VI) | 18595 | N-[3-([[tert-butyl(diphenyl)silyl]oxy]methyl)-2,4-dichlorophenyl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-methylacetamide | C34H32Cl2N2O4Si | 详情 | 详情 | |
| (VII) | 18596 | N-[2,4-dichloro-3-(hydroxymethyl)phenyl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-methylacetamide | C18H14Cl2N2O4 | 详情 | 详情 | |
| (VIII) | 18597 | 2,6-dichloro-3-[[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl](methyl)amino]benzyl methanesulfonate | C19H16Cl2N2O6S | 详情 | 详情 | |
| (IX) | 18598 | 2-methyl-8-quinolinol | 826-81-3 | C10H9NO | 详情 | 详情 |
| (X) | 18599 | N-(2,4-dichloro-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenyl)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-methylacetamide | C28H21Cl2N3O4 | 详情 | 详情 | |
| (XI) | 18600 | 2-amino-N-(2,4-dichloro-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenyl)-N-methylacetamide | C20H19Cl2N3O2 | 详情 | 详情 |