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【结 构 式】 
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【分子编号】40655 【品名】4-Methyl-1-piperazinamine; 1-Amino-4-methylpiperazine; 4-Methyl-1-piperazinylamine 【CA登记号】6928-85-4 |
【 分 子 式 】C5H13N3 【 分 子 量 】115.17844 【元素组成】C 52.14% H 11.38% N 36.48% |
合成路线1
该中间体在本合成路线中的序号：(XIII)The piperazine (IX) was alkylated with benzyl bromoacetate (X) to give ester (XI), which was converted to carboxylic acid (XII) by catalytic hydrogenolysis of the benzyl ester group. Then, coupling of (XII) with 1-amino-4-methylpiperazine (XIII) produced the corresponding hydrazide. Finally, treatment with fumaric acid in EtOH generated the title fumarate salt.
| 【1】 Matsuo, M.; Hagiwara, D.; Manabe, T.; Konishi, N.; Shigenaga, S.; Murano, K.; Matsuda, H.; Miyake, H. (Fujisawa Pharmaceutical Co., Ltd.); 1-Benzoyl-2-(indolyl-3-alkyl)-piperazine derivs. as neurokinin receptor antagonists. EP 0846116; JP 1999505830; WO 9637489 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 44730 | [3,5-bis(trifluoromethyl)phenyl][(2R)-2-(1H-indol-3-ylmethyl)piperazinyl]methanone | C22H19F6N3O | 详情 | 详情 | |
| (X) | 12869 | benzyl 2-bromoacetate | 5437-45-6 | C9H9BrO2 | 详情 | 详情 |
| (XI) | 44732 | benzyl 2-[(3R)-4-[3,5-bis(trifluoromethyl)benzoyl]-3-(1H-indol-3-ylmethyl)piperazinyl]acetate | C31H27F6N3O3 | 详情 | 详情 | |
| (XII) | 44733 | 2-[(3R)-4-[3,5-bis(trifluoromethyl)benzoyl]-3-(1H-indol-3-ylmethyl)piperazinyl]acetic acid | C24H21F6N3O3 | 详情 | 详情 | |
| (XIII) | 40655 | 4-Methyl-1-piperazinamine; 1-Amino-4-methylpiperazine; 4-Methyl-1-piperazinylamine | 6928-85-4 | C5H13N3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)The oxidation of methyl O-methylpodocarpate (I) with chromium trioxide produced ketone (II). This was then condensed with 1-amino-4-methylpiperazine (III) to yield the title hydrazone.
| 【1】 Sachs, R.K.; Hornback, W.J.; Tang, J.; Munroe, J.E.; In vitro and in vivo activity of a series of influenza A inhibitors derived from podocarpic acid. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F950. |
| 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) | 26922 | methyl (1S,4aS,10aR)-6-methoxy-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydro-1-phenanthrenecarboxylate | C19H26O3 | 详情 | 详情 | |
| (II) | 40654 | methyl (1S,4aS)-6-methoxy-1,4a-dimethyl-9-oxo-1,2,3,4,4a,9,10,10a-octahydro-1-phenanthrenecarboxylate | C19H24O4 | 详情 | 详情 | |
| (III) | 40655 | 4-Methyl-1-piperazinamine; 1-Amino-4-methylpiperazine; 4-Methyl-1-piperazinylamine | 6928-85-4 | C5H13N3 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(X)The reductocondensation of 3-bromo-4-fluorobenzaldehyde (I) with morpholine (II) by means of NaBH(OAc)3 in dichloroethane gives 4-(3-bromo-4-fluorobenzyl)morpholine (III), which is condensed with N-methoxy-N-methylacetamide (IV) by means of BuLi in THF to yield 1-[2-fluoro-5-(4-morpholinylmethyl)phenyl]ethanone (V). The reaction of (V) with an excess diethyl carbonate (VI) by means of NaH affords the 3-oxopropanoate derivative (VII), which is treated with triethyl orthoformate (VIII) and Ac2O at 150 C to provide the ethoxymethylene compound (IX). The reaction of (IX) with piperazine-1-amine (X) in ethanol gives the aminomethylene derivative (XI), which is cyclized by means of NaH in hot THF to yield the quinolone-3-carboxylate (XII). Finally, this compound is condensed with 4-chlorobenzylamine (XIII) by heating at 190 C to afford the target quinolone-3-carboxamide.
| 【1】 Pargas, R.E.M.; Tucker, J.A.; Schnute, M.E.; et al.; 1-Amino-4-oxo-1,4-dihydroquinolines with broad-spectrum antiherpetic activity. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-1669. |
| 【2】 Thaisrivongs, S.; Strohbach, J.W.; Turner, S.R.; Vaillancourt, V.A.; Tucker, J.A.; Schnute, M.E. (Pharmacia Corp.); Quinolinecarboxamides as antiviral agents. EP 1140850; US 6248739; WO 0040561 . |
| 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) | 51550 | 3-Bromo-4-fluorobenzaldehyde | 77771-02-9 | C7H4BrFO | 详情 | 详情 |
| (II) | 10388 | Morpholine | 110-91-8 | C4H9NO | 详情 | 详情 |
| (III) | 53185 | 4-(3-bromo-4-fluorobenzyl)morpholine | n/a | C11H13BrFNO | 详情 | 详情 |
| (IV) | 17426 | N-methoxy-N-methylacetamide | 78191-00-1 | C4H9NO2 | 详情 | 详情 |
| (V) | 53186 | 1-[2-fluoro-5-(4-morpholinylmethyl)phenyl]-1-ethanone | n/a | C13H16FNO2 | 详情 | 详情 |
| (VI) | 17470 | diethyl carbonate; diethylcarbonate | 105-58-8 | C5H10O3 | 详情 | 详情 |
| (VII) | 53187 | ethyl 3-[2-fluoro-5-(4-morpholinylmethyl)phenyl]-3-oxopropanoate | n/a | C16H20FNO4 | 详情 | 详情 |
| (VIII) | 21304 | Triethyl orthoformate; 1-(Diethoxymethoxy)ethane; Diethoxymethyl ethyl ether | 122-51-0 | C7H16O3 | 详情 | 详情 |
| (IX) | 53188 | ethyl (Z)-3-ethoxy-2-[2-fluoro-5-(4-morpholinylmethyl)benzoyl]-2-propenoate | n/a | C19H24FNO5 | 详情 | 详情 |
| (X) | 40655 | 4-Methyl-1-piperazinamine; 1-Amino-4-methylpiperazine; 4-Methyl-1-piperazinylamine | 6928-85-4 | C5H13N3 | 详情 | 详情 |
| (XI) | 53189 | ethyl (Z)-2-[2-fluoro-5-(4-morpholinylmethyl)benzoyl]-3-[(4-methyl-1-piperazinyl)amino]-2-propenoate | n/a | C22H31FN4O4 | 详情 | 详情 |
| (XII) | 53190 | ethyl 1-(4-methyl-1-piperazinyl)-6-(4-morpholinylmethyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylate | n/a | C22H30N4O4 | 详情 | 详情 |
| (XIII) | 23378 | (4-chlorophenyl)methanamine; 4-chlorobenzylamine | 104-86-9 | C7H8ClN | 详情 | 详情 |