2,7-dichloroquinoxaline -Drug Synthesis Database

【结构式】

【分子编号】56725

【品名】2,7-dichloroquinoxaline

【CA登记号】59489-31-5

【分子式】C₈H₄Cl₂N₂

【分子量】199.03864

【元素组成】C 48.28% H 2.03% Cl 35.62% N 14.07%

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：(VI)

The reaction of (S)(-)-lactic acid methyl ester (I) with Ts-Cl and TEA in dichloromethane gives the corresponding tosylate (II), which is condensed with 4-(benzyloxy)phenol (III) by means of NaH in DMF to yield (R)(+)-2-[4-(benzyloxy)phenoxy]propionic acid methyl ester (IV). The hydrogenolysis of the benzyl group of (IV) with H2 over Pd/C in ethyl acetate affords the 4-hydroxyphenoxy compound (V), which is condensed with 2,7-dichloroquinoxaline (VI) by means of K2CO3 in refluxing acetone, provides the ester precursor (VII). The hydrolysis of (VII) with KOH in THF/water, followed by acidification with HCl, gives the chiral propionic acid (VIII), which is finally converted into its sodium salt with NaOH in water.

参考文献中间体

合成目标

【1】 Behrens, C.H.; Dusak, B.A.; Harrison, B.A.; Orwat, M.J. (Bristol-Myers Squibb Co.); (2-Quinoxalinyloxy)phenoxypropanoic acids and related derivs. as anticancer agents. WO 9413647 .

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)	17075	propionic acid, 2-hydroxy-, methyl ester, (S)-; methyl (2S)-2-hydroxypropanoate	27871-49-4	C₄H₈O₃	详情	详情
(II)	56722	methyl (2S)-2-{[(4-methylphenyl)sulfonyl]oxy}propanoate		C₁₁H₁₄O₅S	详情	详情
(III)	18956	4-(Benzyloxy)phenol; 4-Benzyloxyphenol	103-16-2	C₁₃H₁₂O₂	详情	详情
(IV)	56723	methyl (2R)-2-[4-(benzyloxy)phenoxy]propanoate		C₁₇H₁₈O₄	详情	详情
(V)	56724	methyl (2R)-2-(4-hydroxyphenoxy)propanoate		C₁₀H₁₂O₄	详情	详情
(VI)	56725	2,7-dichloroquinoxaline	59489-31-5	C₈H₄Cl₂N₂	详情	详情
(VII)	56726	methyl (2R)-2-{4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy}propanoate		C₁₈H₁₅ClN₂O₄	详情	详情
(VIII)	56727	(2R)-2-{4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy}propanoic acid		C₁₇H₁₃ClN₂O₄	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 cyclization of 4-chlorophenylene-1,2-diamine (I) with glyoxylic acid (II) in isopropanol gives a mixture of 7-chloroquinoxalin-2-ol (III) and 6-chloroquinoxalin-2-ol (IV), which, without isolation is treated with refluxing POCl3, and the resulting mixture of dichloro compounds is submitted to flash chromatography to obtain the desired 2,7-dichloroquinoxaline (V). The condensation of (V) with 2-(4-hydroxyphenoxy)propionic acid methyl ester (VI) by means of K2CO3 in refluxing acetone affords the ester precursor (VII), which is hydrolyzed with KOH in THF/water and acidified with HCl to provide the racemic 2-[4-(7-chloroquinoxalin-2-yloxy)phenoxy]propionic acid (VIII). Finally, this compound is converted into its sodium salt with NaOH in water.

参考文献中间体

合成目标

【1】 Behrens, C.H.; Dusak, B.A.; Harrison, B.A.; Orwat, M.J. (Bristol-Myers Squibb Co.); (2-Quinoxalinyloxy)phenoxypropanoic acids and related derivs. as anticancer agents. WO 9413647 .

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)	55570	2-Amino-5-chlorobenzamide; 3,4-Diaminochlorobenzene; 4-Chloro-1,2-diaminobenzene; 4-Chloro-1,2-phenylenediamine; 4-Chloro-o-phenylenediamine	95-83-0	C₆H₇ClN₂	详情	详情
(II)	15618	2-Oxoacetic acid; Glyoxylic Acid	298-12-4	C₂H₂O₃	详情	详情
(III)	56728	7-chloro-2-quinoxalinol		C₈H₅ClN₂O	详情	详情
(IV)	56729	6-chloro-2-quinoxalinol		C₈H₅ClN₂O	详情	详情
(V)	56725	2,7-dichloroquinoxaline	59489-31-5	C₈H₄Cl₂N₂	详情	详情
(VI)	56730	Methyl D-2-(4-hydroxyphenoxy)propionate	96562-58-2	C₁₀H₁₂O₄	详情	详情
(VII)	56731	methyl 2-{4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy}propanoate		C₁₈H₁₅ClN₂O₄	详情	详情
(VIII)	56732	2-{4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy}propanoic acid		C₁₇H₁₃ClN₂O₄	详情	详情

Extended Information