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【结 构 式】 
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【药物名称】JJC-1-059 【化学名称】cis-N-[3-[3,5-Dimethyl-4-(3-phenylpropyl)-1-piperazinyl]propyl]-N,N-Bis(4-fluorophenyl)amine 【CA登记号】 【 分 子 式 】C30H37F2N3 【 分 子 量 】477.64629 |
【开发单位】National Institute on Drug Abuse (Originator) 【药理作用】Treatment of Cocaine Dependency, TREATMENT OF POISONING, DRUG ABUSE & DEPENDENCY, Treatment of Substance Dependency, Dopamine Transporter (DAT) Inhibitors |
合成路线1
The CuI-assisted coupling between methyl N-(4-fluorophenyl)carbamate (I) and 1-bromo-4-fluorobenzene (II) produced the N,N-bis(4-fluorophenyl)carbamate (III), which was subsequently hydrolyzed to bis(4-fluorophenyl)amine (IV) using ethanolic KOH. Acylation of diarylamine (IV) with 3-bromopropionyl chloride (V) gave bromopropionamide (VI). This was then condensed with cis-2,6-dimethylpiperazine (VII) to yield the 3-piperazinylpropionamide (VIII). Amide reduction with LiAlH4 provided the triamino compound (IX). Acid chloride (XI), prepared from hydrocinnamic acid (X), was then coupled with piperazine (IX) to furnish amide (XII). The amide function was finally reduced to the corresponding amine by using LiAlH4.
| 【1】 Cao, J.; Husbands, S.M.; Kopajtic, T.; Newman, A.H.; Katz, J.L.; [3-cis-3,5-Dimethyl-(1-piperazinyl)alkyl]-bis-(4'-fluorophenyl)amine analogues as novel for the dopamine transporter. Bioorg Med Chem Lett 2001, 11, 24, 3169. |
| 【2】 Ca, J.; Newman, A.H.; Kopajtic, T.; Katz, J.L.; Husbands, S.M.; [3-cis-3,5-Dimethyl-1-piperazinyl)alkyl]-bis-(4'-fluorophenyl)amines analogs as novel probes for the dopamine transporter. 221st ACS Natl Meet (April 1 2001, San Diego) 2001, Abst MEDI 96. |
| 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) | 49174 | methyl 4-fluorophenylcarbamate | C8H8FNO2 | 详情 | 详情 | |
| (II) | 29012 | 1-bromo-4-fluorobenzene | 460-00-4 | C6H4BrF | 详情 | 详情 |
| (III) | 49175 | methyl bis(4-fluorophenyl)carbamate | C14H11F2NO2 | 详情 | 详情 | |
| (IV) | 49176 | 4-fluoro-N-(4-fluorophenyl)aniline; N,N-bis(4-fluorophenyl)amine | C12H9F2N | 详情 | 详情 | |
| (V) | 49177 | 3-Bromopropionyl chloride; beta-Bromopropionyl chloride | 15486-96-1 | C3H4BrClO | 详情 | 详情 |
| (VI) | 49178 | 3-bromo-N,N-bis(4-fluorophenyl)propanamide | C15H12BrF2NO | 详情 | 详情 | |
| (VII) | 20848 | (2R,6S)-2,6-dimethylpiperazine | C6H14N2 | 详情 | 详情 | |
| (VIII) | 49179 | 3-[(3R,5S)-3,5-dimethylpiperazinyl]-N,N-bis(4-fluorophenyl)propanamide | C21H25F2N3O | 详情 | 详情 | |
| (IX) | 49180 | N-[3-[(3R,5S)-3,5-dimethylpiperazinyl]propyl]-N,N-bis(4-fluorophenyl)amine; N-[3-[(3R,5S)-3,5-dimethylpiperazinyl]propyl]-4-fluoro-N-(4-fluorophenyl)aniline | C21H27F2N3 | 详情 | 详情 | |
| (X) | 49181 | Hydrocinnamic acid; 3-Phenylpropionic acid; Benzylacetic acid | 501-52-0 | C9H10O2 | 详情 | 详情 |
| (XI) | 16240 | 3-phenylpropanoyl chloride; Hydrocinnamoylchloride | 645-45-4 | C9H9ClO | 详情 | 详情 |
| (XII) | 49182 | 1-((2R,6S)-4-[3-[bis(4-fluorophenyl)amino]propyl]-2,6-dimethylpiperazinyl)-3-phenyl-1-propanone | C30H35F2N3O | 详情 | 详情 |