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【结 构 式】 
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【分子编号】25915 【品名】4-methoxy-3-(4-methyl-1-piperazinyl)phenylamine; 4-methoxy-3-(4-methyl-1-piperazinyl)aniline 【CA登记号】 |
【 分 子 式 】C12H19N3O 【 分 子 量 】221.30248 【元素组成】C 65.13% H 8.65% N 18.99% O 7.23% |
合成路线1
该中间体在本合成路线中的序号：(II)By condensation of 1-(2-phenylethyl)piperazine (I) with 4-methoxy-3-(4-methyl-1-piperazinyl)aniline (II) and triphosgene by means of triethylamine in dichloromethane.
| 【1】 Jorand-Lebrun, C.; et al.; Synthesis and pharmacological studies of a new 5HT1B/1D receptors inverse agonist. 15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998, Edinburgh) 1998, Abst P.162. |
| 【2】 Jorand-Lebrun, C.; Pauwels, P.; Chopin, P.; Marien, M.; Halazy, S. (Pierre Fabre Médicament); Novel aromatic piperazines derived from substd. cycloazanes, method for preparing same, pharmaceutical compsns., and use thereof as drugs. JP 2000505795; WO 9728141 . |
合成路线2
该中间体在本合成路线中的序号：(I)Treatment of 4-methoxy-3-(4-methylpiperazin-1-yl)aniline dihydrochloride (I) with 1,1'-carbonyldiimidazole (II) gave the intermediate imidazolide (III) which, upon treatment with 4-(5-fluoro-1H-indol-3-yl)piperidine (IV) afforded the unsymmetrical urea. Finally, treatment with HCl in acetone yielded the title hydrochloride salt.
| 【1】 Seyfried, C.AS.; van Amsterdam, C.; Rautenberg, W.; Matzen, L.; Harting, J.; Greiner, H.E.; Bottcher, H.; 5-HT reuptake inhibitors with 5-HT1B/1D antagonistic activity: A new approach toward efficient antidepressants. J Med Chem 2000, 43, 6, 1149. |
| 【2】 Bottcher, H.; Harting, J.; van Amsterdam, C.; Bartoszyk, G.; Greiner, H.; Rautenberg, W.; Matzen, L. (Merck Patent GmbH); Amide and urea derivs.. DE 19756036 . |
| 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) | 25915 | 4-methoxy-3-(4-methyl-1-piperazinyl)phenylamine; 4-methoxy-3-(4-methyl-1-piperazinyl)aniline | C12H19N3O | 详情 | 详情 | |
| (II) | 11353 | 1,1'-Carbonyldiimidazole; Di(1H-imidazol-1-yl)methanone; N,N-Carbonyldiimidazole; 1,1'-Carbonylbis(1H-imidazole) | 530-62-1 | C7H6N4O | 详情 | 详情 |
| (III) | 40360 | N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-1H-imidazole-1-carboxamide | C16H21N5O2 | 详情 | 详情 | |
| (IV) | 40361 | 5-fluoro-3-(4-piperidinyl)-1H-indole | C13H15FN2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)The title sulfonamide was prepared by coupling 4-methoxy-3-(4-methylpiperazin-1-yl)aniline (II) with 4-iodobenzenesulfonyl chloride (I) in acetone.
| 【1】 Bromidge, S.M.; Brown, A.M.; Clarke, S.E.; Dodgson, K.; Gager, T.; Grassam, H.L.; Jeffrey, P.M.; Joiner, G.F.; King, F.D.; Middlemiss, D.N.; Moss, S.F.; Newman, H.; Riley, G.; Routledge, C.; Wyman, P.; 5-Chloro-N-(4-methoxy-3-piperazin-1-ylphenyl)-3-methyl-2-benzothiophenesulfonamide (SB-271046): A potent, selective, and orally bioavailable 5-HT6 receptor antagonist. J Med Chem 1999, 42, 2, 202. |
| 【2】 King, F.D.; Bromidge, S.M.; Wyman, P.A. (SmithKline Beecham plc); Sulphonamide derivs., process for their preparation, and their use as medicaments. WO 9827081 . |
合成路线4
该中间体在本合成路线中的序号：(II)Coupling of 4-bromobenzoyl chloride (I) with amine (II) by means of Et3N in CH2Cl2 or THF yields bromo derivative (III), which is then converted into boronic acid derivative (IV) by treatment with triisopropyloxyboron and n-BuLi in THF/hexane. Suzuki reaction between (IV) and oxadiazole (V) by means of Pd(PPd3)4 and Na2CO3 in dimethoxyethane (DME)/H2O affords compound (VI), which is finally hydrogenated over Raney-Ni in H2O/MeOH/AcOH to furnish the desired product.
| 【1】 März, J.; Cremers, T.; Harting, J.; Liao, Y.; Wikstrom, H.; Rautenberg, W.; Greiner, H.; Sundell, S.; Böttcher, H.; van Amsterdam, C.; New selective and potent 5-HT1B/1D antagonists: Chemistry and pharmacological evaluation of N-piperazinylphenyl biphenylcarboxamides and biphenylsulfonamides. J Med Chem 2000, 43, 3, 517. |
| 【2】 Van Amsterdam, C.; Harting, J.; Wikstrom, H.V.; Liao, Y.; Bottcher, H. (Merck Patent GmbH); Biphenyl derivs.. WO 0005225 . |
| 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) | 45960 | 4-bromobenzoyl chloride | 586-75-4 | C7H4BrClO | 详情 | 详情 |
| (II) | 25915 | 4-methoxy-3-(4-methyl-1-piperazinyl)phenylamine; 4-methoxy-3-(4-methyl-1-piperazinyl)aniline | C12H19N3O | 详情 | 详情 | |
| (III) | 45961 | 4-bromo-N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]benzamide | C19H22BrN3O2 | 详情 | 详情 | |
| (IV) | 45964 | 4-[[4-methoxy-3-(4-methyl-1-piperazinyl)anilino]carbonyl]phenylboronic acid | C19H24BN3O4 | 详情 | 详情 | |
| (V) | 45962 | 3-(4-bromo-3-methylphenyl)-5-methyl-1,2,4-oxadiazole | C10H9BrN2O | 详情 | 详情 | |
| (VI) | 45963 | C28H32BrN5O3 | 详情 | 详情 |