【结 构 式】 |
【分子编号】26413 【品名】N-(5-formyl-2-pyridinyl)acetamide 【CA登记号】 |
【 分 子 式 】C8H8N2O2 【 分 子 量 】164.1638 【元素组成】C 58.53% H 4.91% N 17.06% O 19.49% |
合成路线1
该中间体在本合成路线中的序号:(X)The condensation of 2-methylquinolin-8-ol (I) with 2,6-dichloro-3-nitrobenzyl chloride (II) by means of NaH in DMF gives the corresponding benzyl ether (III), which is reduced with Fe and HCl in methanol/water to the aniline (IV). The acylation of (IV) with 2-phthalimidoacetyl chloride (V) by means of DMAP and pyridine yields the amide (VI), which is methylated at the amidic nitrogen with NaH and methyl iodide in DMF to the N-methylanilide (VII). Elimination of the phthalimido group of (VII) with hydrazine in refluxing ethanol affords the glycine anilide (VIII), which is acylated with the acrylic acid (IX) by means of 1-[3-dimethylamino)propyl]-3-ethylcarbodiimide (DECD) and HOBT in DMF. The intermediate substituted acrylic acid (IX) has been obtained by reaction of 6-acetamidopyridine-3-carbaldehyde (X) with malonic acid and pyridine in refluxing ethanol.
【1】 Oku, T.; Kayakiri, H.; Satoh, S.; Abe, Y.; Sawada, Y.; Inoue, T.; Tanaka, H. (Fujisawa Pharmaceutical Co., Ltd.); Pyridopyrimidones, quinolines and fused N-heterocycles as bradykinin antagonists. EP 0807105; JP 1998507764; WO 9613485 . |
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) | 18598 | 2-methyl-8-quinolinol | 826-81-3 | C10H9NO | 详情 | 详情 |
(II) | 18928 | 1,3-dichloro-2-(chloromethyl)-4-nitrobenzene | C7H4Cl3NO2 | 详情 | 详情 | |
(III) | 18929 | 2,6-dichloro-3-nitrobenzyl 2-methyl-8-quinolinyl ether; 8-[(2,6-dichloro-3-nitrobenzyl)oxy]-2-methylquinoline | C17H12Cl2N2O3 | 详情 | 详情 | |
(IV) | 18930 | 2,4-dichloro-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenylamine; 2,4-dichloro-3-[[(2-methyl-8-quinolinyl)oxy]methyl]aniline | C17H14Cl2N2O | 详情 | 详情 | |
(V) | 10278 | 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | 6780-38-7 | C10H6ClNO3 | 详情 | 详情 |
(VI) | 18932 | N-(2,4-dichloro-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenyl)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetamide | C27H19Cl2N3O4 | 详情 | 详情 | |
(VII) | 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 | |
(VIII) | 18600 | 2-amino-N-(2,4-dichloro-3-[[(2-methyl-8-quinolinyl)oxy]methyl]phenyl)-N-methylacetamide | C20H19Cl2N3O2 | 详情 | 详情 | |
(IX) | 19304 | (E)-3-[6-(acetamido)-3-pyridinyl]-2-propenoic acid | C10H10N2O3 | 详情 | 详情 | |
(X) | 26413 | N-(5-formyl-2-pyridinyl)acetamide | C8H8N2O2 | 详情 | 详情 | |
(XI) | 12963 | Malonic acid | 141-82-2 | C3H4O4 | 详情 | 详情 |