CDB-4124, Progenta

Chemical Name: 17alpha-Acetoxy-11beta-[4-(dimethylamino)phenyl]-21-methoxy-19-norpregna-4,9-diene- 3,20-dione
CAS No. 198414-31-2
项目整合开发状态: Phase II
项目研究机构: National Cancer Institute (Originator), Zonagen (Licensee)
合成路线:Protection of cyanohydrin ketal (I) with bromomethyldimethylsilyl chloride (A) in presence of DMAP and Et3N affords derivative (II),which is converted into (III) by means of LDA in cyclohexane and aqueous HBr.Treatment of (III) with KOAc in acetone yields acetoxy derivative (IV),which is then hydrolyzed to provide (V) by means of KHCO3 in refluxing MeOH.Protection of (V) as its acetal form by treatment with ethylene glycol in p-TsOH affords (VI),which is converted into methyl ether (VII) by treatment with Me3O+BF4- in presence of 1,8-bis(dimethylamino)-naphthalene.Oxidation of (VII) by means of H2O2,Na2HPO4 and (CF3)2CO in CH2Cl2 yields epoxide (VIII),which is converted into (X) by a Grignard reaction with (IX) in THF followed by treatment with CuCl.Diketal (X) is then deprotected by means of TFA in THF to provide derivative (XI),which is finally acetylated with (CF3CO)2O in a mixture of HOAc,p-TsOH and CH2Cl2.