|
【结 构 式】 
|
【药物名称】 【化学名称】2-[3-[4-(3-Chlorophenyl)-2(S)-methylpiperazinyl]propyl]-1,2,4-triazolo[4,3-a]pyridin-3(2H)-one L-(+)-tartrate 【CA登记号】161968-03-2, 161905-64-2 (free base), 161968-06-5 (maleate salt (1:1)), 161968-05-4 (sulfate(1:1)) 【 分 子 式 】C24H30ClN5O7 【 分 子 量 】535.989 |
【开发单位】Angelini (Originator) 【药理作用】Antidepressants, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, 5-HT2A Antagonists |
合成路线1
The reaction of 3-chloroaniline (I) with ethanolamine (II) by means of 47% HBr by heating at 170 C gives N-(3-chlorophenyl)ethylenediamine (III), which is condensed with ethyl 2-bromopropionate (IV) by means of triethylamine in refluxing toluene yielding the alanine derivative (V). The cyclization of (V) with refluxing 2N HCl affords the piperazinone (VI), which is reduced with LiAlH4 in ethyl ether providing 1-(3-chlorophenyl)-3-methylpiperazine (VII). The alkylation of (VII) with 1-bromo-3-chloropropane (VIII) by means of NaOH in acetone/water gives 4-(3-chlorophenyl)-1-(3-chloropropyl)-2-methylpiperazine (IX), which is condensed with the sodium salt of 1,2,4-triazolo[4,3-a]pyridin-3(2H)-one (X) in refluxing xylene/isobutanol yielding the target compound as a racemic mixture (XI). Finally, this compound is submitted to optical resolution with L-(+)-tartaric acid (XII).
| 【1】 Giannangeli, M.; Gazzolla, N.; Luparini, M.R.; Magnani, M.; Mabilia, M.; Picconi, G.; Tomaselli, M.; Baiocchi, L.; Effect of modifications of the alkylpiperazine moiety of trazodone on 5HT2A and alpha1 receptor binding affinity. J Med Chem 1999, 42, 3, 336. |
| 【2】 Baiocchi, L.; Cioli, V. (Angelini Group); Pharmacologically active enantiomers. EP 0707587; JP 1996512036; WO 9501354 . |
| 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) | 25239 | 3-chloroaniline; 3-chlorophenylamine | 108-42-9 | C6H6ClN | 详情 | 详情 |
| (II) | 10259 | Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol | 141-43-5 | C2H7NO | 详情 | 详情 |
| (III) | 34091 | N(1)-(3-chlorophenyl)-1,2-ethanediamine; N-(2-aminoethyl)-N-(3-chlorophenyl)amine | C8H11ClN2 | 详情 | 详情 | |
| (IV) | 19460 | ethyl 2-bromopropanoate; 2-Bromopropionic acid ethyl ester | 535-11-5 | C5H9BrO2 | 详情 | 详情 |
| (V) | 28373 | ethyl 2-[[2-(3-chloroanilino)ethyl]amino]propanoate | C13H19ClN2O2 | 详情 | 详情 | |
| (VI) | 28374 | 1-(3-chlorophenyl)-3-methyl-2-piperazinone | C11H13ClN2O | 详情 | 详情 | |
| (VII) | 28375 | 1-(3-chlorophenyl)-3-methylpiperazine | C11H15ClN2 | 详情 | 详情 | |
| (VIII) | 10358 | 1-Bromo-3-chloropropane | 109-70-6 | C3H6BrCl | 详情 | 详情 |
| (IX) | 28376 | 4-(3-chlorophenyl)-1-(3-chloropropyl)-2-methylpiperazine | C14H20Cl2N2 | 详情 | 详情 | |
| (X) | 28377 | [3-oxo[1,2,4]triazolo[4,3-a]pyridin-2(3H)-yl]sodium | C6H4N3NaO | 详情 | 详情 | |
| (XI) | 28378 | 2-[3-[4-(3-chlorophenyl)-2-methyl-1-piperazinyl]propyl][1,2,4]triazolo[4,3-a]pyridin-3(2H)-one | C20H24ClN5O | 详情 | 详情 | |
| (XII) | 28379 | (2R,3R)-2,3-dihydroxybutanedioic acid; L-Tartaric acid; (2R,3R)-2,3-dihydroxysuccinic acid | 87-69-4 | C4H6O6 | 详情 | 详情 |