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【结 构 式】 
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【分子编号】59823 【品名】(2S)-2-methylpiperazine 【CA登记号】 |
【 分 子 式 】C5H12N2 【 分 子 量 】100.16376 【元素组成】C 59.96% H 12.08% N 27.97% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)The chiral piperazine building block (XVIII) was prepared as follows. L-Alanine ethyl ester (XV) was condensed with formaldehyde and NaCN to give the amino nitrile (XVI). Catalytic hydrogenation of the cyano group of (XVI) with simultaneous intramolecular cyclization furnished the piperazinone (XVII). This was reduced to the target (S)-2-methylpiperazine (XVIII) by means of LiAlH4 (1).
| 【1】 Iwata, M.; Kimura, T.; Inoue, T.; Fujihara, Y.; Katsube, T. (Sankyo Co., Ltd.; Ube Industries, Ltd.); 4-Oxoquinoline-3-carboxylic acid derivs., their preparation and their use. AU 8938218; EP 0352123; EP 0610958; JP 1990124873; JP 1990231476; JP 1993255183; US 5002947; US 5073556; US 5348961 . |
合成路线2
该中间体在本合成路线中的序号：(XVIII)Condensation of fluoroquinolone (XIV) with piperazine (XVIII) afforded the piperazinyl quinolone adduct (XIX). Then, boron chelate cleavage in (XIX) by refluxing in the presence of Et3N, followed by treatment with HCl provided the title compound
| 【1】 Iwata, M.; Kimura, T.; Inoue, T.; Fujihara, Y.; Katsube, T. (Sankyo Co., Ltd.; Ube Industries, Ltd.); 4-Oxoquinoline-3-carboxylic acid derivs., their preparation and their use. AU 8938218; EP 0352123; EP 0610958; JP 1990124873; JP 1990231476; JP 1993255183; US 5002947; US 5073556; US 5348961 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIV) | 59818 | 1-cyclopropyl-3-{[(difluoroboryl)oxy]carbonyl}-8-(difluoromethoxy)-6,7-difluoro-4(1H)-quinolinone | C14H8BF6NO4 | 详情 | 详情 | |
| (XVIII) | 59823 | (2S)-2-methylpiperazine | C5H12N2 | 详情 | 详情 | |
| (XIX) | 59824 | 1-cyclopropyl-3-{[(difluoroboryl)oxy]carbonyl}-8-(difluoromethoxy)-6-fluoro-7-[(3S)-3-methylpiperazinyl]-4(1H)-quinolinone | C19H19BF5N3O4 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)Alkylation of (R)-2-methylpiperazine (I) with 4-fluorobenzyl bromide (II) provides 1-(4-fluorobenzyl)-3-methylpiperazine (III). Subsequent acylation of piperazine (III) with (4-chlorophenoxy)acetyl chloride (IV) furnishes the title amide.
| 【1】 Monahan, S.D.; Xu, W.; Morissey, M.M.; Bauman, J.G.; Ng, H.P.; Hesselgesser, J.E.; Liang, M.; Zheng, W.; Islam, I.; May, K.B.; Ghannam, A.F.; Buckman, B.O.; Horuk, R.; Wei, G.P. (Schering AG); Piperazine derivs. and their use as anti-inflammatory agents. US 6207665; WO 9856771 . |