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【结 构 式】 
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【药物名称】O-1057 【化学名称】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 【CA登记号】216988-51-1, 216988-52-2 (free base) 【 分 子 式 】C32H47ClN2O4 【 分 子 量 】559.19539 |
【开发单位】Organix (Originator), Virginia Commonwealth University (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Non-Opioid Analgesics, Cannabinoid CB1 Agonists, Cannabinoid CB2 Agonists |
合成路线1
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.
| 【1】 Razdan, R.K.; Martin, B.R. (Virginia Commonwealth University); Water soluble derivs. of cannabinoids. US 5847128 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 47231 | 3,5-dimethoxybenzonitrile | 19179-31-8 | C9H9NO2 | 详情 | 详情 |
| (II) | 47232 | 4-bromobutyl phenyl ether; 1-(4-bromobutoxy)benzene | 1200-03-9 | C10H13BrO | 详情 | 详情 |
| (III) | 47233 | 1-(3,5-dimethoxyphenyl)-5-phenoxy-1-pentanone | C19H22O4 | 详情 | 详情 | |
| (IV) | 47234 | 1-(1,1-dimethyl-5-phenoxypentyl)-3,5-dimethoxybenzene; 5-(3,5-dimethoxyphenyl)-5-methylhexyl phenyl ether | C21H28O3 | 详情 | 详情 | |
| (V) | 47235 | 5-(5-bromo-1,1-dimethylpentyl)-1,3-benzenediol | C13H19BrO2 | 详情 | 详情 | |
| (VI) | 46586 | (1S,4R)-4-(1-hydroxy-1-methylethyl)-1-methyl-2-cyclohexen-1-ol | C10H18O2 | 详情 | 详情 | |
| (VII) | 47236 | (6aR,10aR)-3-(5-bromo-1,1-dimethylpentyl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-ol | C23H33BrO2 | 详情 | 详情 | |
| (VIII) | 47237 | 6-[(6aR,10aR)-1-hydroxy-6,6,9-trimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-3-yl]-6-methylheptanenitrile | C24H33NO2 | 详情 | 详情 | |
| (IX) | 47238 | 4-(3-carboxypropyl)morpholin-4-ium chloride | C8H16ClNO3 | 详情 | 详情 |