2-Chloro-4-(chloromethyl)quinoline -Drug Synthesis Database

【结构式】

【分子编号】10290

【品名】2-Chloro-4-(chloromethyl)quinoline

【CA登记号】

【分子式】C₁₀H₇Cl₂N

【分子量】212.07772

【元素组成】C 56.63% H 3.33% Cl 33.43% N 6.6%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(III)

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.

参考文献中间体

合成目标

【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：(III)

2) The same reaction sequence of (I) and (IVr) yields intermediates (Vs), (VIs) and (VIIs), and finally (S)-OPC-12759.

参考文献中间体

合成目标

【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

Extended Information