【结 构 式】 |
【分子编号】10322 【品名】1-Methyl-3-phenylpiperazine 【CA登记号】5271-27-2 |
【 分 子 式 】C11H16N2 【 分 子 量 】176.26152 【元素组成】C 74.96% H 9.15% N 15.89% |
合成路线1
该中间体在本合成路线中的序号:(II)2) [14C]-Labeled: The condensation of 2-chloro-3-nitropyridine (I) with 1-methyl-3-phenylpiperazine (II) by means of KF at 140 C in DMF gives 4-methyl-1-(3-nitropyridin-2-yl)-2-phenylpiperazine (III), which is reduced with H2 over Pd/C in ethanol to the amine (IV). The reaction of (IV) with pentyl nitrite and bromoform at 100 C yields 1-(3-bromopyridin-2-yl)-4-methyl-2-phenylpiperazine (V), which by reaction with butyllithium and [14C]-labeled CO2 in ether is converted into 2-(4-methyl-2-phenylpiperazin-1-yl)pyridine-3-carboxylic acid (VI). The reduction of (VI) with LiAlH4 in hot THF affords the corresponding alcohol (VII), which is finally cyclized in hot H2SO4.
【1】 Wieringa, J.H.; Kaspersen, F.M.; van Rooij, F.A.M.; Sperling, E.G.M.; The synthesis of ORG 3770 labelled with 3H, 13C and 14C. J Label Compd Radiopharm 1989, 27, 9, 1055. |
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) | 10321 | 2-Chloro-3-nitropyridine | 5470-18-8 | C5H3ClN2O2 | 详情 | 详情 |
(II) | 10322 | 1-Methyl-3-phenylpiperazine | 5271-27-2 | C11H16N2 | 详情 | 详情 |
(III) | 10323 | 4-Methyl-1-(3-nitro-2-pyridinyl)-2-phenylpiperazine | C16H18N4O2 | 详情 | 详情 | |
(IV) | 10324 | 2-(4-Methyl-2-phenylpiperazino)-3-pyridinamine; 2-(4-Methyl-2-phenylpiperazino)-3-pyridinylamine | C16H20N4 | 详情 | 详情 | |
(V) | 10325 | 1-(3-Bromo-2-pyridinyl)-4-methyl-2-phenylpiperazine | C16H18BrN3 | 详情 | 详情 | |
(VI) | 10326 | 2-(4-Methyl-2-phenylpiperazino)nicotinic acid | C17H19N3O2 | 详情 | 详情 | |
(VI) | 44646 | 2-(4-methyl-2-phenyl-1-piperazinyl)nicotinic acid | C17H19N3O2 | 详情 | 详情 | |
(VII) | 10320 | [2-(4-Methyl-2-phenylpiperazino)-3-pyridinyl]methanol | 61337-89-1 | C17H21N3O | 详情 | 详情 |
(VII) | 44647 | [2-(4-methyl-2-phenyl-1-piperazinyl)-3-pyridinyl]methanol | C17H21N3O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(II)Reaction of 2-chloronicotinonitrile (I) with 1-methyl-3-phenylpiperazine (II) gives 2-(4-methyl-2-phenyl-1-piperazinyl)-3-pyridinecarbonitrile (III), which is hydrolyzed to the carboxylic acid, which is reducted to the hydroxymethyl derivative (IV). Cyclization of (IV) in concentrated sulfuric acid at 20-35 C gives the title compound after 2 h and treatment with ammonia.
【1】 Van der Burg, W.J. (Akzo Nobel N.V.); Tetracyclic compounds. BE 0840362; CH 622261; DE 2614406; DK 142498; ES 446634; FR 2305986; GB 1543171; JP 76122099; NL 754075 . |
【2】 Koch, H.; Azamianserin. Drugs Fut 1985, 10, 12, 965. |
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) | 10308 | 2-Chloronicotinonitrile; 2-Chloro-3-cyanopyridine | 6602-54-6 | C6H3ClN2 | 详情 | 详情 |
(II) | 10322 | 1-Methyl-3-phenylpiperazine | 5271-27-2 | C11H16N2 | 详情 | 详情 |
(III) | 29819 | 2-(4-methyl-2-phenyl-1-piperazinyl)nicotinonitrile | C17H18N4 | 详情 | 详情 | |
(IV) | 10320 | [2-(4-Methyl-2-phenylpiperazino)-3-pyridinyl]methanol | 61337-89-1 | C17H21N3O | 详情 | 详情 |