O-1057

4-吗啡丁酸(6aR,10aR)-3-(5-氰基-1,1-二甲基戊基)-6,6,9-三甲基-6a,7,10,10a-四氢-6H-苯并[c]-1-苯并吡喃-1-基酯盐酸酯Chemical Name: 4-Morpholinebutanoic acid (6aR,10aR)-3-(5-cyano-1,1-dimethylpentyl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]-1-benzopyran-1-yl ester hydrochloride
CAS No. 216988-51-1, 216988-52-2 (free base)
项目整合开发状态: Preclinical
项目研究机构: Organix (Originator), Virginia Commonwealth University (Originator)
合成路线:Grignard reaction between 3,5-dimethyoxybenzonitrile (I) and 4-bromophenoxybutane (II) in the presence of Mg turnings in THF,followed by hydrolysis with HCl,affords ketone (III),which is then treated with TiCl4 in dichloromethane and dimethyl zinc (Me2Zn) in toluene to provide dimethylpentane derivative (IV).Bromination of (IV) is then accomplished by first azeotroping with benzene followed by treatment with BBr3 in dichloromethane,affording bromo derivative (V).Condensation of resorcinol derivative (V) with p-menth-2-ene-1,8-diol (VI) in refluxing benzene in the presence of p-toluensulfonic acid furnishes compound (VII),whose bromo group is substituted by a cyano group by treatment with NaCN in DMSO giving derivative (VIII).Finally,condensation of (VIII) with 4-morpholinobutyric acid hydrochloride (IX) by means of DCC in dichloromethane provides the target product.