(R)-(+)-XK-469, NSC-698215(free acid), XB-947

Chemical Name: (+)-2(R)-[4-(7-Chloroquinoxalin-2-yloxy)phenoxy]propionic acid sodium salt
项目整合开发状态: Phase I
项目研究机构: Bristol-Myers Squibb (Originator), National Cancer Institute (Not Determined)
合成路线: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.

合成路线: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.