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【结 构 式】 
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【药物名称】L-Deprenyl hydrochloride, Selegiline hydrochloride, FPF-1100, E-250(free base), Zydis selegilline, Deprenyl, Vivapryl, Zelapar, FP, Plurimen, Seledat, Eldepryl, Jumex 【化学名称】(-)-(R)-N,alpha-Dimethyl-N-(2-propynyl)phenethylamine hydrochloride 【CA登记号】14611-52-0, 14611-51-9 (free base) 【 分 子 式 】C13H18ClN 【 分 子 量 】223.74811 |
【开发单位】Chiesi (Originator), Chinoin (Originator), Schering-Plough (Not Determined), Amarin (Licensee), Asta Medica (Licensee), Elan (Licensee), Fujimoto (Licensee), Orion Pharma (Licensee), Sarget (Licensee), Somerset (Licensee) 【药理作用】Antiparkinsonian Drugs, Extrapyramidal Disorders, Treatment of, NEUROLOGIC DRUGS, Treatment of Cocaine Dependency, TREATMENT OF POISONING, DRUG ABUSE & DEPENDENCY, Treatment of Substance Dependency, MAO-B Inhibitors |
合成路线1
Compound can be prepared in several related ways: 1) The condensation of N-(1-phenylisopropyl)methylamine (I) with 1,2-dibromopropene (A) by heating at 100 C gives N-(1-phenylisopropyl)-N-methyl-2-bromopropenylamine (II), which is then dehydrobrominated and isomerized by treating with KOH in refluxing ethanol water. 2) By heating a mixture of (I) and propargyl bromide (B) at 100 C. 3) By reductocondensation of (I) with propargyl aldehyde (C) by means of amalgamated Al in ethanol. 4) By condensation of (I) with formaldehyde and acetylene by means of CuCl in hot dioxane. 5) By condensation of 1-phenylisopropyl chloride (III) with N-methylpropargylamine (IV) by heating at 80 C in a sealed tube.
| 【1】 Ecsery, Z.; et al.; AT 252901 . |
| 【2】 Ecsery, Z.; et al.; AT 251560 . |
| 【3】 Ecsery, Z.; et al.; Verfahren zur Herstellung von Phenylisopropylaminen. DE 1568277; NL 6605956 . |
| 【4】 Ecsery, Z.; et al.; Verfahren zur Herstellung von Phenylisopropylaminen. CH 530953; DE 1227447 . |
| 【5】 Roberts, P.J.; Castaner, J.; Selegiline. Drugs Fut 1979, 4, 2, 128. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 23634 | acetylene | 74-86-2 | C2H2 | 详情 | 详情 | |
| (B) | 11176 | 3-Bromopropyne; 3-Bromo-1-propyne | 106-96-7 | C3H3Br | 详情 | 详情 |
| (A) | 33322 | (E)-1,2-dibromo-1-propene | 26391-16-2 | C3H4Br2 | 详情 | 详情 |
| (I) | 33321 | N-methyl-N-[(1R)-1-methyl-2-phenylethyl]amine; (2R)-N-methyl-1-phenyl-2-propanamine | 537-46-2 | C10H15N | 详情 | 详情 |
| (II) | 33323 | N-[(E)-3-bromo-2-butenyl]-N-methyl-N-[(1R)-1-methyl-2-phenylethyl]amine; (E)-3-bromo-N-methyl-N-[(1R)-1-methyl-2-phenylethyl]-2-buten-1-amine | C14H20BrN | 详情 | 详情 | |
| (III) | 33324 | 1-[(2R)-2-chloropropyl]benzene | C9H11Cl | 详情 | 详情 | |
| (IV) | 33325 | N-methyl-2-propyn-1-amine; N-methyl-N-(2-propynyl)amine | C4H7N | 详情 | 详情 | |
| (C) | 23544 | propiolaldehyde | C3H2O | 详情 | 详情 |
合成路线2
The reduction of 11C-CO2 (I) by means of LiAlH4 in THF gives 11C-methanol (II), which is treated with 57 % IH to yield 11C-methyl iodide (III). The reaction of (III) with silver triflate affords 11C-methyl triflate (IV). Finally, (R)(-)-nor-selegiline (nor-deprenil) (V) is methylated with the radiolabeled methyl triflate (IV) by means of NaOH in aqueous acetone to obtain the target radiolabeled compound.
| 【1】 Dolle, F.; et al.; Efficient synthesis and formulation of (R)-(-)-[11C]deprenyl, a selective radioligand for the quantification of MAO-B activity using PET. J Label Compd Radiopharm 2002, 45, 10, 803. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 58598 | methanol | CH4O | 详情 | 详情 | |
| (III) | 58599 | iodomethane | CH3I | 详情 | 详情 | |
| (IV) | 17414 | methyl trifluoromethane sulfonate; methyl trifluoromethanesulfonate | 333-27-7 | C2H3F3O3S | 详情 | 详情 |
| (IV) | 45233 | methyl trifluoromethanesulfonate | C2H3F3O3S | 详情 | 详情 | |
| (V) | 58600 | N-[(1R)-1-methyl-2-phenylethyl]-2-propyn-1-amine; N-[(1R)-1-methyl-2-phenylethyl]-N-(2-propynyl)amine | C12H15N | 详情 | 详情 |