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【结 构 式】 
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【分子编号】20796 【品名】N-(Benzhydryl)piperazine; 1-Benzhydrylpiperazine; 1-(dibenzyl)piperazine 【CA登记号】841-77-0 |
【 分 子 式 】C17H20N2 【 分 子 量 】252.35928 【元素组成】C 80.91% H 7.99% N 11.1% |
合成路线1
该中间体在本合成路线中的序号：(II)By condesation of 4-(2,3-epoxypropoxy)-1H-indole-2-carbonitrile (I) with 1-(diphenylmethyl)piperazine (II).
| 【1】 Belleau, B.; Nguyen-Ba, N. (BioChem Pharma Inc.); Use of 1,3-oxathiolane nucleoside analogues in the treatment of hepatitis B. EP 0494119; JP 1994507150; US 5532246; WO 9211852 . |
| 【2】 Koch, H.; DPI-201106. Drugs Fut 1985, 10, 12, 979. |
合成路线2
该中间体在本合成路线中的序号：(I)By condensation of 4-diphenylmethylpiperazine (I) with 1-(3-chloropropyl)-2-benzimidazolone (II) by means of Na2CO3 in refluxing 4-methyl-2-pentanone.
| 【1】 Yan, F.; et al.; Piperazine and piperidine derivative. BE 0852405; JP 61005068; ZA 7702000 . |
| 【2】 Church, M.K.; Castaner, J.; Oxatomide. Drugs Fut 1978, 3, 6, 465. |
| 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) | 20796 | N-(Benzhydryl)piperazine; 1-Benzhydrylpiperazine; 1-(dibenzyl)piperazine | 841-77-0 | C17H20N2 | 详情 | 详情 |
| (II) | 33440 | 1-(3-chloropropyl)-1,3-dihydro-2H-benzimidazol-2-one; 1-(3-Chloropropyl)benzimidazole-2-one; 1-(3-Chloropropyl)-2-benzimidazolidinone | 62780-89-6 | C10H11ClN2O | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)The reaction of 1-(diphenylmethyl)piperazine (I) with 3,4-dimethoxyphenacyl bromide (II) by means of triethylamine in isopropanol gives alpha-[4-(diphenylmethyl)-1-piperazinyl]-3,4-dimethoxyacetophenone (III), which is then reduced with NaBH4 in ethanol-CHCl3.
| 【1】 Mitsuo, M. (Nippon Chemiphar Co., Ltd.); New piperazine derivs., their salts and pharmaceuticals for improving cerebral circulation. DE 3326148; ES 8603449 . |
| 【2】 Prous, J.; Castaner, J.; NC-1100. Drugs Fut 1989, 14, 4, 334. |
| 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) | 20796 | N-(Benzhydryl)piperazine; 1-Benzhydrylpiperazine; 1-(dibenzyl)piperazine | 841-77-0 | C17H20N2 | 详情 | 详情 |
| (II) | 20797 | 2-bromo-1-(3,4-dimethoxyphenyl)-1-ethanone | C10H11BrO3 | 详情 | 详情 | |
| (III) | 20798 | 2-(4-benzhydryl-1-piperazinyl)-1-(3,4-dimethoxyphenyl)-1-ethanone | C27H30N2O3 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(I)The title compound was synthesized by alkylation of 1-benzhydrylpiperazine (I) with 2-(3-chloropropyl)-2-phenyl-1,3-dioxolan (II) in the presence of NaHCO3 in refluxing EtOH.
| 【1】 Foguet, R.; Gubert, S.; Raga, M.M.; Ortiz, J.A.; Sacristan, A. (Ferrer Internacional SA); Piperazine derivs., a process for preparing them and pharmaceutical compsns.. EP 0097340 . |
合成路线5
该中间体在本合成路线中的序号：(VI)The reaction of 3-acetyl-6-methyl-3,4-dihydro-2H-pyran-2,4-dione (I) with ammonia gives 2,6-dimethylpyridin-4-ol (II), which is nitrated with HNO3/H2SO4 and treated with SOCl2 to yield 4-chloro-2,6-dimethyl-3-nitropyridine (III). The condensation of (III) with ethanolamine (IV) affords N-(2,6-dimethyl-3-nitropyridin-4-yl)ethanolamine (V), which is finally condensed with 1-(diphenylmethyl)piperazine (VI) by means of SOCl2 and treated with HCl to furnish the target trihydrochloride.
| 【1】 (Aventis SA); Pyridine derivs.. DE 3541428; EP 0224159; JP 1987129271; US 4792554 . |
| 【2】 Elben, U.; SUBSTITUTED DIALKYLPYRIDINES AND THEIR N-OXIDES WITH AN ELECTRON-WITHDRAWING SUBSTITUENT. Drugs Fut 1989, 14, 10, 981. |
| 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) | 43660 | 3-acetyl-6-methyl-2H-pyran-2,4(3H)-dione | 520-45-6 | C8H8O4 | 详情 | 详情 |
| (II) | 43661 | 2,6-dimethyl-4-pyridinol | C7H9NO | 详情 | 详情 | |
| (III) | 43662 | 4-chloro-2,6-dimethyl-3-nitropyridine | C7H7ClN2O2 | 详情 | 详情 | |
| (IV) | 10259 | Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol | 141-43-5 | C2H7NO | 详情 | 详情 |
| (V) | 43663 | 2-[(2,6-dimethyl-3-nitro-4-pyridinyl)amino]-1-ethanol | C9H13N3O3 | 详情 | 详情 | |
| (VI) | 20796 | N-(Benzhydryl)piperazine; 1-Benzhydrylpiperazine; 1-(dibenzyl)piperazine | 841-77-0 | C17H20N2 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(II)Condensation of N-Boc-L-aspartic acid gamma-benzyl ester (I) with N-benzhydryl piperazine (II) using 1-ethyl-3-(3-dimethylaminopropyl)- carbodiimide hydrochloride (EDC) and 1-hydroxybenzotriazole (HOBT) as the condensig agents gave amide (III). Reduction of the ester group of (III) with NaBH4 in refluxing EtOH provided alcohol (IV), which was treated with methanesulfonyl chloride to afford mesylate (V). Subsequent reaction of (V) with sodium azide in N,N'-dimethylimidazolidinone gave azide (VI), and further cycloaddition of this azide with methyl propiolate (VII) in refluxing dichloroethane furnished triazole (VIII). The tert-butoxycarbonyl protecting group of (VIII) was then removed by treatment with trifluoroacetic acid at room temperature to yield amine (IX), which was condensed with indole-2-carboxylic acid (X) in the presence of EDC and HOBT to give amide (XI). Finally, hydrolysis of (XI) with LiOH provided the target carboxylic acid.
| 【1】 Ogawa, M.; Morita, T.; Matsuda, K.; Iibuchi, N.; Kidokoro, S. (Tobishi Pharmaceutical Co.); Amino acid deriv. having anti-CKK activity. EP 0710661; JP 1996119940; JP 1996176144; US 5716958 . |
| 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) | 25219 | (2S)-4-(benzyloxy)-2-[(tert-butoxycarbonyl)amino]-4-oxobutyric acid | 7536-58-5 | C16H21NO6 | 详情 | 详情 |
| (II) | 20796 | N-(Benzhydryl)piperazine; 1-Benzhydrylpiperazine; 1-(dibenzyl)piperazine | 841-77-0 | C17H20N2 | 详情 | 详情 |
| (III) | 25220 | benzyl (3S)-4-(4-benzhydryl-1-piperazinyl)-3-[(tert-butoxycarbonyl)amino]-4-oxobutanoate | C33H39N3O5 | 详情 | 详情 | |
| (IV) | 25221 | tert-butyl (1S)-1-[(4-benzhydryl-1-piperazinyl)carbonyl]-3-hydroxypropylcarbamate | C26H35N3O4 | 详情 | 详情 | |
| (V) | 25222 | (3S)-4-(4-benzhydryl-1-piperazinyl)-3-[(tert-butoxycarbonyl)amino]-4-oxobutyl methanesulfonate | C27H37N3O6S | 详情 | 详情 | |
| (V) | 25223 | tert-butyl (1S)-3-azido-1-[(4-benzhydryl-1-piperazinyl)carbonyl]propylcarbamate | C26H34N6O3 | 详情 | 详情 | |
| (VII) | 19588 | methyl propiolate | 922-67-8 | C4H4O2 | 详情 | 详情 |
| (VIII) | 25224 | methyl 1-[(3S)-4-(4-benzhydryl-1-piperazinyl)-3-[(tert-butoxycarbonyl)amino]-4-oxobutyl]-1H-1,2,3-triazole-5-carboxylate | C30H38N6O5 | 详情 | 详情 | |
| (IX) | 25225 | methyl 1-[(3S)-3-amino-4-(4-benzhydryl-1-piperazinyl)-4-oxobutyl]-1H-1,2,3-triazole-5-carboxylate | C25H30N6O3 | 详情 | 详情 | |
| (X) | 25226 | 1H-Indole-2-carboxylic acid; Indole-2-carboxylic acid | 1477-50-5 | C9H7NO2 | 详情 | 详情 |
| (XI) | 25227 | methyl 1-[(3S)-4-(4-benzhydryl-1-piperazinyl)-3-[(1H-indol-2-ylcarbonyl)amino]-4-oxobutyl]-1H-1,2,3-triazole-5-carboxylate | C34H35N7O4 | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(VI)Condensation of trimethylhydroquinone (I) with 4-chloro-1-butanol (II) in the presence of phosphomolybdic acid in refluxing toluene yielded the chlorobutyl ether (III). Benzhydrylpiperazine (VI), (prepared from chlorodiphenylmethane (IV) and piperazine (V)), was then condensed with chloride (III) to give the target compound, which was isolated as the dihydrochloride salt.
| 【1】 Kawasaki, N.; Satoh, T.; Nagai, H.; Nishiki, M.; Matsumoto, H.; Inagaki, N.; Miyataka, H.; Synthesis of trimethylhydroquinone derivatives as anti-allergic agents with anti-oxidative actions. Chem Pharm Bull 1999, 47, 2, 177. |
| 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) | 26357 | 2,3,5-trimethyl-1,4-benzenediol | 700-13-0 | C9H12O2 | 详情 | 详情 |
| (II) | 22336 | 4-chloro-1-butanol | 928-51-8 | C4H9ClO | 详情 | 详情 |
| (III) | 27973 | 4-(4-chlorobutoxy)-2,3,6-trimethylphenol | C13H19ClO2 | 详情 | 详情 | |
| (IV) | 27974 | Benzhydrylchloride; 1,1-Diphenylchloromethane; Dibenzyl chloride; Alpha-Chlorodiphenylmethane; Chlorodiphenylmethane; Diphenylchloromethane; 1-[chloro(phenyl)methyl]benzene | 90-99-3 | C13H11Cl | 详情 | 详情 |
| (V) | 10355 | Diethylenediamine; Piperazine | 110-85-0 | C4H10N2 | 详情 | 详情 |
| (VI) | 20796 | N-(Benzhydryl)piperazine; 1-Benzhydrylpiperazine; 1-(dibenzyl)piperazine | 841-77-0 | C17H20N2 | 详情 | 详情 |