|
【结 构 式】 
|
【药物名称】 【化学名称】cis-4-[N-(1-Allyl-3-methylpiperidin-4-yl)-N-phenylamino]-N,N-diethylbenzamide 【CA登记号】229478-44-8, 244048-67-7 (hydrochloride) 【 分 子 式 】C26H35N3O 【 分 子 量 】405.58835 |
【开发单位】Ortho-McNeil (Originator), Research Triangle Institute (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Opioid Analgesics, delta-Opioid Agonists |
合成路线1
Condensation of 1,3-dimethyl-4-piperidone (I) with aniline in the presence of titanium tetraisopropoxide produced imine (II). This was reduced with NaBH4 to give the corresponding amine as a mixture of geometric isomers, from which the desired cis isomer (III) was isolated by column chromatography. Coupling of (III) with 4-fluorobenzoate ester (IV) in the presence of butyllithium yielded the diaryl amine (V). Removal of the 2,6-di-tert-butyl-4-methoxyphenyl ester of (V) was accomplished by transesterification with sodium methoxide, followed by saponification of the methyl ester. The resulting carboxylic acid (VI) was then converted into diethyl amide (VII) using diethylamine and BOP reagent. N-Demethylation of (VII) with phenyl chloroformate furnished the phenyl carbamate (VIII), that was further hydrolyzed and decarboxylated to give piperidine (IX). This was finally alkylated with allyl bromide in the presence of K2CO3.
| 【1】 Carroll, F.I.; Thomas, J.B.; Dersch, C.M.; Rothman, R.B.; Mascarella, S.W.; Burges, J.P.; Xu, H.; Herault, X.M.; Horel, R.B.; (±)-4-[(N-Allyl-cis-3-methyl-4-piperidinyl)phenylamino]-N,N-diethylbenzamide displays selective binding for the delta opioid receptor. Bioorg Med Chem Lett 1999, 9, 20, 3053. |
| 【2】 Carroll, F.I.; Novel opiate cpds., methods of making and methods of use. WO 9945925 . |
| 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) | 16614 | 1,3-dimethyltetrahydro-4(1H)-pyridinone; 1,3-Dimethyl-4-piperidone | 4629-80-5 | C7H13NO | 详情 | 详情 |
| (II) | 41966 | N-(1,3-dimethyl-4-piperidinylidene)-N-phenylamine; N-(1,3-dimethyl-4-piperidinylidene)aniline | C13H18N2 | 详情 | 详情 | |
| (III) | 41968 | N-[(3R,4S)-1,3-dimethylpiperidinyl]-N-phenylamine; (3R,4S)-1,3-dimethyl-N-phenyl-4-piperidinamine | C13H20N2 | 详情 | 详情 | |
| (IV) | 41458 | 2,6-di(tert-butyl)-4-methoxyphenyl 4-fluorobenzoate | C22H27FO3 | 详情 | 详情 | |
| (V) | 41969 | 2,6-di(tert-butyl)-4-methoxyphenyl 4-[[(3R,4S)-1,3-dimethylpiperidinyl]anilino]benzoate | C35H46N2O3 | 详情 | 详情 | |
| (VI) | 41970 | 4-[[(3R,4S)-1,3-dimethylpiperidinyl]anilino]benzoic acid | C20H24N2O2 | 详情 | 详情 | |
| (VII) | 41971 | 4-[[(3R,4S)-1,3-dimethylpiperidinyl]anilino]-N,N-diethylbenzamide | C24H33N3O | 详情 | 详情 | |
| (VIII) | 41967 | phenyl (3R,4S)-4-[4-[(diethylamino)carbonyl](phenyl)anilino]-3-methyl-1-piperidinecarboxylate | C30H35N3O3 | 详情 | 详情 | |
| (IX) | 41972 | N,N-diethyl-4-[[(3R,4S)-3-methylpiperidinyl]anilino]benzamide | C23H31N3O | 详情 | 详情 |