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【结 构 式】 
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【分子编号】35066 【品名】isopropyl 2-(1-piperazinyl)phenyl ether; 1-(2-isopropoxyphenyl)piperazine 【CA登记号】 |
【 分 子 式 】C13H20N2O 【 分 子 量 】220.31468 【元素组成】C 70.87% H 9.15% N 12.72% O 7.26% |
合成路线1
该中间体在本合成路线中的序号：(I)The intermediate amine (IV) was prepared by alkylation of N-(2-isopropoxyphenyl)piperazine (I) with N-(2-bromoethyl)phthalimide (II), followed by removal of the phthaloyl group upon treatment with methylhydrazine.
| 【1】 Murray, W.V.; Jolliffe, L.; Pulito, V.; Li, X.; Novel arylpiperazines as selective alpha1-adrenergic receptor antagonists. Bioorg Med Chem Lett 2000, 10, 10, 1093. |
| 【2】 Mulcahy, L.; Pulito, V.; Villani, F.; Li, X.; Murray, W.; Maryanoff, C.; Jolliffe, L.; Reitz, A. (Ortho-McNeil Pharmaceutical, Inc.); Arylsubstd. piperazines useful in the treatment of benign prostatic hyperplasia. EP 0984777; US 6071915; WO 9851298 . |
| 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) | 35066 | isopropyl 2-(1-piperazinyl)phenyl ether; 1-(2-isopropoxyphenyl)piperazine | C13H20N2O | 详情 | 详情 | |
| (II) | 37025 | 2-(2-bromoethyl)-1H-isoindole-1,3(2H)-dione | 574-98-1 | C10H8BrNO2 | 详情 | 详情 |
| (III) | 43364 | 2-[2-[4-(2-isopropoxyphenyl)-1-piperazinyl]ethyl]-1H-isoindole-1,3(2H)-dione | C23H27N3O3 | 详情 | 详情 | |
| (IV) | 43365 | 2-[4-(2-isopropoxyphenyl)-1-piperazinyl]ethylamine; 2-[4-(2-isopropoxyphenyl)-1-piperazinyl]-1-ethanamine | C15H25N3O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)Alkylation of 1-(2-isopropoxyphenyl)piperazine (I) with 1-azido-3-(p-toluenesulfonyloxy)-2-propanol (II) in hot NMP gave (III). Subsequent hydrogenation of the azido group of (III) over Pd/C provided the intermediate amine (IV).
| 【1】 Prouty, C.; Wang, J.; Kuo, G.-H.; Pulito, V.; Murray, W.V.; Cheung, P.; Jolliffe, L.; Varga, S.; Evangelisto, M.; Design, synthesis, and structure-activity relationships of phthalimide-phenylpiperazines: A novel series of potent and selective alpha1a-adrenergic receptor antagonists. J Med Chem 2000, 43, 11, 2183. |
| 【2】 Murray, W.V.; Kuo, G.-H.; Prouty, C.P. (Ortho-McNeil Pharmaceutical, Inc.); Phthalimido arylpiperazines as alpha 1a receptor antagonists useful in the treatment of benign prostatic hyperplasia. US 6063785; WO 9942445 . |
| 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) | 35066 | isopropyl 2-(1-piperazinyl)phenyl ether; 1-(2-isopropoxyphenyl)piperazine | C13H20N2O | 详情 | 详情 | |
| (II) | 35067 | (2S)-3-azido-2-hydroxypropyl 4-methylbenzenesulfonate | C10H13N3O4S | 详情 | 详情 | |
| (III) | 35068 | (2R)-1-azido-3-[4-(2-isopropoxyphenyl)-1-piperazinyl]-2-propanol | C16H25N5O2 | 详情 | 详情 | |
| (IV) | 35069 | (2S)-1-amino-3-[4-(2-isopropoxyphenyl)-1-piperazinyl]-2-propanol | C16H27N3O2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)(S)-Epichlorhydrin (V) was treated with benzylamine to afford aminoalcohol (VI). After protection of the amino group of (VI) as the tert-butyl carbamate (VII) with Boc2O, displacement of the chlorine of (VII) with arylpiperazine (I) furnished (VIII). Deprotection of the N-Boc group of (VIII) by means of trifluoroacetic acid gave (IX). Then, the N-benzyl group of (IX) was removed by transfer hydrogenolysis employing ammonium formate and Pd/C to provide the intermediate amine (IV).
| 【1】 Prouty, C.; Wang, J.; Kuo, G.-H.; Pulito, V.; Murray, W.V.; Cheung, P.; Jolliffe, L.; Varga, S.; Evangelisto, M.; Design, synthesis, and structure-activity relationships of phthalimide-phenylpiperazines: A novel series of potent and selective alpha1a-adrenergic receptor antagonists. J Med Chem 2000, 43, 11, 2183. |
| 【2】 Murray, W.V.; Kuo, G.-H.; Prouty, C.P. (Ortho-McNeil Pharmaceutical, Inc.); Phthalimido arylpiperazines as alpha 1a receptor antagonists useful in the treatment of benign prostatic hyperplasia. US 6063785; WO 9942445 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 详情 | 详情 | |
| (I) | 35066 | isopropyl 2-(1-piperazinyl)phenyl ether; 1-(2-isopropoxyphenyl)piperazine | C13H20N2O | 详情 | 详情 | |
| (IV) | 35069 | (2S)-1-amino-3-[4-(2-isopropoxyphenyl)-1-piperazinyl]-2-propanol | C16H27N3O2 | 详情 | 详情 | |
| (V) | 13917 | (S)-Epichlorohydrin; (2S)-2-(Chloromethyl)oxirane;(S)-(+)-epichlorohydrin | 67843-74-7 | C3H5ClO | 详情 | 详情 |
| (VI) | 35070 | (2S)-1-(benzylamino)-3-chloro-2-propanol | C10H14ClNO | 详情 | 详情 | |
| (VII) | 35071 | tert-butyl benzyl[(2S)-3-chloro-2-hydroxypropyl]carbamate | C15H22ClNO3 | 详情 | 详情 | |
| (VIII) | 35072 | tert-butyl benzyl[(2R)-2-hydroxy-3-[4-(2-isopropoxyphenyl)-1-piperazinyl]propyl]carbamate | C28H41N3O4 | 详情 | 详情 | |
| (IX) | 35073 | (2S)-1-(benzylamino)-3-[4-(2-isopropoxyphenyl)-1-piperazinyl]-2-propanol | C23H33N3O2 | 详情 | 详情 |