GS-7904, OSI-7904, GW-1843U89, GW-1843, BW-1843U89, 1843U89

(S)-2-(5-((3-甲基-1-氧基-1,2-二氢苯并喹啷-9-基)甲基)氨基)-1-氧异吹哆啰-2-基)戊二酸Chemical Name: 2(S)-[5-[3-Methyl-1-oxo-1,2-dihydrobenzo[f]quinazolin-9-ylmethylamino]-1-oxo-2,3-dihydro-1H-isoindol-2-yl]pentanedioic acid
CAS No. 139987-54-5
项目整合开发状态: Phase I
项目研究机构: GlaxoSmithKline (Originator), Gilead (Licensee), OSI (Licensee)
合成路线:The condensation of L-glutamic acid diethyl ester (I) with 4-nitrophthalic anhydride (II) by means of DIEA in refluxing toluene gives the 4-nitrophthalimide (III),which is reduced with H2 over Pd/C to yield the 4-aminophthalimide (IV).The reduction of (IV) with Zn/HCl in ethanol affords a 3:1 mixture of the 5-aminoisoindolinone (V) and 6-aminoisoindolinone (VI) that is separated by chromatography.The desired isomer (V) is condensed with 9-(bromomethyl)-3-methylbenzo[f]quinazolin-1(2H)-one (VII) (obtained by bromination of 3,9-dimethylbenzo[f]quinazolin-1(2H)-one (VIII) with NBS) in DMF at 110?C to provide the precursor (IX).Finally,the ester groups of (IX) are hydrolyzed with NaOH in methanol.