L-695256

Chemical Name: (5R,6S)-6-[1(R)-Hydroxyethyl]-2-[7-(1-methylimidazolium-3-ylmethyl)-9-oxofluoren-3-yl]-1-carba-2-penem-3-carboxylate
CAS No. 137323-79-6
项目整合开发状态: Preclinical
项目研究机构: Merck & Co. (Originator)
合成路线:The bromination of 6-bromo-2-methylfluoren-9-one (I) with NBS and AIBN in refluxing CCl4 gives the 2-bromomethyl compound (II),which is treated with potassium acetate in DMF to afford the acetoxymethyl derivative (III).The hydrolysis of (III) with NaOMe in methanol provides the hydroxymethyl compound (IV),which is treated with hexamethyldistannane and Pd(PPh3)4 in refluxing toluene to give the trimethylstannyl derivative (V).The condensation of (V) with the carbapenem triflate (VI) by means of a Pd catalyst in THF yields the adduct (VII),which is condensed with 1-methylimidazole by means of Tf2O in dichloromethane affording the imidazolium derivative (IX).The desilylation of (IX) with TBAF in THF gives the 1-hydroxyethyl derivative (X),which is finally treated with H2 over Pd/C in THF/ethanol/water to obtain the target compound as an inner salt.The intermediate carbapenem triflate (VI) has been obtained by reaction of 2-oxocarbapenam (XI) with Tf2O,followed by silylation with Tes-OTf.