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【结 构 式】 
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【分子编号】20616 【品名】(E)-3-ethoxy-2-propenoyl chloride 【CA登记号】99471-66-6 |
【 分 子 式 】C5H7ClO2 【 分 子 量 】134.56208 【元素组成】C 44.63% H 5.24% Cl 26.35% O 23.78% |
合成路线1
该中间体在本合成路线中的序号：(A)OPC-8212 is obtained through the piperazine ring formation method from bis(beta-bromoethyl)amine hydrobromide and 6-amino-3,4-dihydro-2(1H)-quinolinone (V) to give (VI). (V) is synthesized using the ring closure reaction of p-acetylamino-beta-ethoxyacryloanilide (II). p-Acetylaminoaniline (I) is converted to (II) by treatment with beta-ethoxyacryloyl chloride and afterwards cyclized in the presence of sulfuric acid to give 6-acetylamino-2-(1H)-quinolinone (III). Hydrogenation of (III) over 10% palladium on charcoal gives 6-acetylamino-3,4-dihydro-2(1H)-quinolinone (IV). Hydrolysis of (IV) gives 6-amino-3,4-dihydro-2(1H)-quinolinone (V). OPC-8212 is obtained by adding 3,4-dimethoxybenzyl chloride (VII) to (VI).
| 【1】 Nakagawa, K.; Osumi, T.; Shimizu, T.; Niimi, K.; Physicochemical properties and stabilities of a new positive inotropic agent, OPC 8212. Arzneim-Forsch Drug Res 1984, 34, 3A, 334-341. |
| 【2】 Yo, E.; Ogawa, H.; Yamashita, S.; Tominaga, M.; Nakagawa, K.; Yabuuchi, Y.; Studies on positive inotropic agents. I. Synthesis of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone and related compounds. Chem Pharm Bull 1984, 32, 6, 2100. |
| 【3】 Mannhold, R.; OPC-8212. Drugs Fut 1985, 10, 1, 28. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 20616 | (E)-3-ethoxy-2-propenoyl chloride | 99471-66-6 | C5H7ClO2 | 详情 | 详情 |
| (B) | 29020 | 2-bromo-N-(2-bromoethyl)-1-ethanamine | C4H9Br2N | 详情 | 详情 | |
| (I) | 29016 | N-(4-aminophenyl)acetamide | 122-80-5 | C8H10N2O | 详情 | 详情 |
| (II) | 29017 | (E)-N-[4-(acetamido)phenyl]-3-ethoxy-2-propenamide | C13H16N2O3 | 详情 | 详情 | |
| (III) | 29018 | N-(2-oxo-1,2-dihydro-6-quinolinyl)acetamide | C11H10N2O2 | 详情 | 详情 | |
| (IV) | 29019 | N-(2-oxo-1,2,3,4-tetrahydro-6-quinolinyl)acetamide | C11H12N2O2 | 详情 | 详情 | |
| (V) | 29022 | 6-amino-3,4-dihydro-2(1H)-quinolinone | C9H10N2O | 详情 | 详情 | |
| (VI) | 29021 | 6-(1-piperazinyl)-3,4-dihydro-2(1H)-quinolinone | C13H17N3O | 详情 | 详情 | |
| (VII) | 13438 | 3,4-Dimethoxybenzoyl chloride | 3535-37-3 | C9H9ClO3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)The condensation of 4-fluoro-2-methylnitrobenzene (I) with 2,4-dimethyl-1H-imidazole (II) by means of Na2CO3 in hot DMF gives 4-(2,4-dimethyl-1H-imidazol-1-yl)-2-methylnitrobenzene (III), which is reduced with SnCl2 in refluxing ethanol yielding the corresponding aniline (IV).The condensation of (IV) with trans-3-ethoxypropenoyl chloride in anhydrous pyridine affords the anilide (VI), which is finally cyclized by means of 98% H2SO4.
| 【1】 Roberts, D.A.; Campbell, S.F. (Pfizer Inc.); Quinolone inotropic agents. AU 8543032; EP 0166533; ES 8608874; ES 8801797; JP 1986000082; US 4728653 . |
| 【2】 Alabaster, C.T.; Bell, A.S.; Campbell, S.F.; Ellis, P.; Henderson, C.G.; Morris, D.S.; Roberts, D.A.; Ruddock, K.S.; Samuels, G.M.R.; Stefaniak, M.H.; 2(1H)-Quinolinones with cardiac stimulant activity. 2. Synthesis and biological activities of 6-(N-linked, five-membered heteroaryl) derivatives. J Med Chem 1989, 32, 3, 575-83. |
| 【3】 Prous, J.; Castaner, J.; NANTERINONE < Prop INN>. Drugs Fut 1989, 14, 4, 328. |
| 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) | 20612 | 4-Fluoro-2-methyl-1-nitrobenzene; 2-Nitro-5-fluorotoluene | 446-33-3 | C7H6FNO2 | 详情 | 详情 |
| (II) | 20613 | 2,4-dimethyl-1H-imidazole | 930-62-1 | C5H8N2 | 详情 | 详情 |
| (III) | 20614 | 2,4-dimethyl-1-(3-methyl-4-nitrophenyl)-1H-imidazole | C12H13N3O2 | 详情 | 详情 | |
| (IV) | 20615 | 4-(2,4-dimethyl-1H-imidazol-1-yl)-2-methylaniline; 4-(2,4-dimethyl-1H-imidazol-1-yl)-2-methylphenylamine | C12H15N3 | 详情 | 详情 | |
| (V) | 20616 | (E)-3-ethoxy-2-propenoyl chloride | 99471-66-6 | C5H7ClO2 | 详情 | 详情 |
| (VI) | 20617 | (E)-N-[4-(2,4-dimethyl-1H-imidazol-1-yl)-2-methylphenyl]-3-ethoxy-2-propenamide | C17H21N3O2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)
| 【1】 Chen B-C,DroghiniR,et aL 2006.Process for preparing 2-aminothiazole-5-carboxamides from thioureas and acrylamides and their use as anticancer drugs. US 2006004067 |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| （V) | 32323 | 4,6-dichloro-2-methylpyrimidine | 1780-26-3 | C5H4Cl2N2 | 详情 | 详情 |
| (I) | 29789 | 2-chloro-6-methylphenylamine; 2-chloro-6-methylaniline | 87-63-8 | C7H8ClN | 详情 | 详情 |
| (II) | 20616 | (E)-3-ethoxy-2-propenoyl chloride | 99471-66-6 | C5H7ClO2 | 详情 | 详情 |
| (III) | 66243 | (E)-N-(2-chloro-6-methylphenyl)-3-ethoxyacrylamide | 863127-76-8 | C12H14ClNO2 | 详情 | 详情 |
| (IV) | 66244 | 2-amino-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide | 302964-24-5 | C11H10ClN3OS | 详情 | 详情 |
| (VI) | 66245 | 2-((6-chloro-2-methylpyrimidin-4-yl)amino)-N-(2-chloro-6-methylphenyl)thiazolidine-5-carboxamide | C16H17Cl2N5OS | 详情 | 详情 | |
| (VII) | 21893 | 2-(1-piperazinyl)-1-ethanol; 1-piperazineethanol; 1-(2-Hydroxyethyl)piperazine | 103-76-4 | C6H14N2O | 详情 | 详情 |