Asoprisnil, J-867

(8S,11R,13S,14S,17S)-11-[4-[(E)-羟基亚氨甲基]苯基]-17-甲氧基-17-(甲氧基甲基)-13-甲基-1,2,6,7,8,11,12,14,15,16-十氢环戊烯并[a]菲-3-酮 Chemical Name: 11beta-[4-[(E)-Hydroxyiminomethyl]phenyl]-17beta-methoxy-17alpha-(methoxymethyl)estra-4,9-dien-3-one
CAS No. 163883-84-9, 199396-76-4
项目整合开发状态: Phase III
项目研究机构: Jenapharm (Originator), Schering AG (Originator), TAP (Licensee)
合成路线:After protection of 4-bromobenzaldehyde (I) with triethyl orthoformate in MeOH,the resultant bromo ketal (II) was converted to the corresponding Grignard reagent (III) with magnesium in THF.Conjugate addition of (III) to the steroid epoxide (IV) in the presence of CuCl gave rise to the 11-beta-aryl steroid (V).Introduction of a 17-spiro oxirane moiety into ketone (V) to yield (VI) was accomplished by reaction with the sulfur ylide generated from trimethylsulfonium iodide and potassium tert-butoxide.Subsequent epoxide opening in (VI) with NaOMe gave rise to the methoxy alcohol (VII),which was further alkylated with iodomethane under Williamson's ether synthesis conditions to provide the dimethoxy derivative (VIII).Acid hydrolysis of both ketal groups of (VIII) with concomitant alcohol dehydration led to the dienone (IX).The aldehyde function of (IX) was finally converted to the target oxime by treatment with hydroxylamine hydrochloride in pyridine.