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【结 构 式】 
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【分子编号】10289 【品名】4-(Bromomethyl)-2-chloroquinoline 【CA登记号】 |
【 分 子 式 】C10H7BrClN 【 分 子 量 】256.52902 【元素组成】C 46.82% H 2.75% Br 31.15% Cl 13.82% N 5.46% |
合成路线1
该中间体在本合成路线中的序号：(II)The synthesis of (R)- and (S)-isomers of OPC-12759 has been described: These optical isomers can be obtained in three different ways: 1) The reaction of 4-(bromomethyl)quinolin-2(1H)-one (I) with hot phosphorus oxychloride gives a mixture of 4-(bromomethyl)-2-chloroquinoline (II) and 2-chloro-4-(chloromethyl)quinoline (III), which, without separation, is condensed with 2(S)-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (IVs) by means of butyllithium in hexane, yielding (-)-2-chloro-4-[6(S)-isopropyl-2,5-dimethoxy-3,6-dihydropyrazin-3(R)-yl methyl]quinoline (Vr). The hydrolysis of (Vr) with HCl affords 3-(2-chloroquinolin-4-yl)-(R)-alanine methyl ester (VIr), which is treated with HCl and propylene oxide to give 3-(2-oxo-2,3-dihydroquinolin-4-yl)-(R)-alanine (VIIr). Finally, this compound is acylated with 4-chlorobenzoyl chloride (VIII) by means of K2CO3 in acetone, affording (R)-OPC-12759.
| 【1】 Morita, S.; Yamasaki, K.; Shimizu, T.; Uchida, M.; Otsubo, K.; Kanbe, T.; Synthesis and antiulcer activity of optical isomers of 2-(4-chlorobenzoy lamino)-3-[2(1H)-quinolinon-4-yl]propionic acid (rebamipide). Chem Pharm Bull 1991, 39, 11, 2906. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IVS) | 10291 | (S)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine; (2S)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine; (3S)-3-Isopropyl-5-methoxy-3,6-dihydro-2-pyrazinyl methyl ether | 78342-42-4 | C9H16N2O2 | 详情 | 详情 |
| (VR) | 10292 | (3R,6S)-3-[(2-Chloro-4-quinolinyl)methyl]-6-isopropyl-5-methoxy-3,6-dihydro-2-pyrazinyl methyl ether; 2-Chloro-4-[[(2R,5S)-5-isopropyl-3,6-dimethoxy-2,5-dihydro-2-pyrazinyl]methyl]quinoline | C19H22ClN3O2 | 详情 | 详情 | |
| (VIR) | 10293 | methyl (2R)-2-amino-3-(2-chloro-4-quinolinyl)propanoate | C13H13ClN2O2 | 详情 | 详情 | |
| (VIIR) | 10294 | (2R)-2-Amino-3-(2-oxo-1,2-dihydro-4-quinolinyl)propionic acid | C12H12N2O3 | 详情 | 详情 | |
| (I) | 10288 | 4-(Bromomethyl)-2(1H)-quinolinone | C10H8BrNO | 详情 | 详情 | |
| (II) | 10289 | 4-(Bromomethyl)-2-chloroquinoline | C10H7BrClN | 详情 | 详情 | |
| (III) | 10290 | 2-Chloro-4-(chloromethyl)quinoline | C10H7Cl2N | 详情 | 详情 | |
| (VIII) | 10295 | p-Chlorobenzoyl chloride; 4-Chlorobenzoyl chloride | 122-01-0 | C7H4Cl2O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)2) The same reaction sequence of (I) and (IVr) yields intermediates (Vs), (VIs) and (VIIs), and finally (S)-OPC-12759.
| 【1】 Morita, S.; Yamasaki, K.; Shimizu, T.; Uchida, M.; Otsubo, K.; Kanbe, T.; Synthesis and antiulcer activity of optical isomers of 2-(4-chlorobenzoy lamino)-3-[2(1H)-quinolinon-4-yl]propionic acid (rebamipide). Chem Pharm Bull 1991, 39, 11, 2906. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IVR) | 10296 | (R)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine; (3R)-3-Isopropyl-5-methoxy-3,6-dihydro-2-pyrazinyl methyl ether; (2R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine | 109838-85-9 | C9H16N2O2 | 详情 | 详情 |
| (VS) | 10297 | 2-Chloro-4-[[(2S,5R)-5-isopropyl-3,6-dimethoxy-2,5-dihydro-2-pyrazinyl]methyl]quinoline; (3R,6S)-6-[(2-Chloro-4-quinolinyl)methyl]-3-isopropyl-5-methoxy-3,6-dihydro-2-pyrazinyl methyl ether | C19H22ClN3O2 | 详情 | 详情 | |
| (VIS) | 10298 | methyl (2S)-2-amino-3-(2-chloro-4-quinolinyl)propanoate | C13H13ClN2O2 | 详情 | 详情 | |
| (VIIS) | 10299 | (2S)-2-Amino-3-(2-oxo-1,2-dihydro-4-quinolinyl)propionic acid | C12H12N2O3 | 详情 | 详情 | |
| (II) | 10289 | 4-(Bromomethyl)-2-chloroquinoline | C10H7BrClN | 详情 | 详情 | |
| (III) | 10290 | 2-Chloro-4-(chloromethyl)quinoline | C10H7Cl2N | 详情 | 详情 | |
| (VIII) | 10295 | p-Chlorobenzoyl chloride; 4-Chlorobenzoyl chloride | 122-01-0 | C7H4Cl2O | 详情 | 详情 |