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【结 构 式】 
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【分子编号】34459 【品名】(3-chlorophenyl)methanamine; 3-chlorobenzylamine 【CA登记号】4152-90-3 |
【 分 子 式 】C7H8ClN 【 分 子 量 】141.59996 【元素组成】C 59.38% H 5.69% Cl 25.04% N 9.89% |
合成路线1
该中间体在本合成路线中的序号：(VII)Salicylaldehyde (I) was alkylated with 1,3-dibromopropane (II) to provide bromopropyl ether (III). Furter displacement of the bromine of (III) with the potassium salt of 2-mercaptoimidazole (IV) gave thioether (V). Condensation of methyl cyanoacetate (VI) with 3-chlorobenzylamine (VII) at 120 C afforded cyanoacetamide (VIII). Finally, Knoevenagel reaction of (VIII) with benzaldehyde (V) in the presence of beta-alanine furnished the title compound.
| 【1】 Gazit, A.; Levitzki, A.; Reuveni, H.; Poradosu, E.; alpha-Cyanocinnamide derivatives: A new family of non-peptide, non-sulfhydryl inhibitors of Ras farnesylation. Bioorg Med Chem 1999, 7, 8, 1727. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 17022 | beta-Alanine; 3-aminopropionic acid | 107-95-9 | C3H7NO2 | 详情 | 详情 | |
| (I) | 21351 | 2-Hydroxybenzaldehyde;Salicylic aldehyde；2-Formylphenol;salicylaldehyde | 90-02-8 | C7H6O2 | 详情 | 详情 |
| (II) | 12581 | 1,3-Dibromopropane | 109-64-8 | C3H6Br2 | 详情 | 详情 |
| (III) | 34455 | 2-(3-bromopropoxy)benzaldehyde | C10H11BrO2 | 详情 | 详情 | |
| (IV) | 34456 | 1H-imidazole-2-thiol; 1H-imidazol-2-ylhydrosulfide | 872-35-5 | C3H4N2S | 详情 | 详情 |
| (V) | 34457 | 2-[3-(1H-imidazol-2-ylsulfanyl)propoxy]benzaldehyde | C13H14N2O2S | 详情 | 详情 | |
| (VI) | 34458 | Cyanoacetic acid methyl ester; methyl 2-cyanoacetate | 105-34-0 | C4H5NO2 | 详情 | 详情 |
| (VII) | 34459 | (3-chlorophenyl)methanamine; 3-chlorobenzylamine | 4152-90-3 | C7H8ClN | 详情 | 详情 |
| (VIII) | 34460 | N-(3-chlorobenzyl)-2-cyanoacetamide | C10H9ClN2O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VIII)Coupling of N-Boc-L-methionine (VIII) with 3-chlorobenzylamine (IX) using PyBOP provided amide (X). Methylation of the sulfide group of (X) with iodomethane gave rise to the sulfonium salt (XI), which was further cyclized to pyrrolidinone (XII) by treatment with lithium bis(trimethylsilyl)amide in cold THF. Acid deprotection of the Boc group of (XII) furnished amine (XIII). This was finally subjected to reductive alkylation with aldehyde (VII) in the presence of sodium cyanoborohydride to provide the corresponding (imidazolylmethyl)amine.
| 【1】 Bell, I.M.; et al.; Design and biological activity of (S)-4-(5-{[1-(3-chlorobenzyl)-2-oxopyrrolidin-3-ylamino]methyl}imidazol-1-ylmethyl)benzonitrile, a 3-aminopyrrolidinone farnesyltransferase inhibitor with excellent cell potency. J Med Chem 2001, 44, 18, 2933. |
| 【2】 Beshore, D.C.; Bell, I.M.; Gallicchio, S.N.; Sisko, J.T.; Zartman, C.B.; Lumma, W.C. Jr. (Merck & Co., Inc.); Inhibitors of prenyl-protein transferase. WO 0117992 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 38388 | 4-[(5-formyl-1H-imidazol-1-yl)methyl]benzonitrile | C12H9N3O | 详情 | 详情 | |
| (VIII) | 34459 | (3-chlorophenyl)methanamine; 3-chlorobenzylamine | 4152-90-3 | C7H8ClN | 详情 | 详情 |
| (IX) | 17634 | (2S)-2-[(tert-butoxycarbonyl)amino]-4-(methylsulfanyl)butyric acid; N-alpha-t-BOC-L-methionine | 2488-15-5 | C10H19NO4S | 详情 | 详情 |
| (X) | 49995 | tert-butyl (1S)-1-[[(3-chlorobenzyl)amino]carbonyl]-3-(methylsulfanyl)propylcarbamate | C17H25ClN2O3S | 详情 | 详情 | |
| (XI) | 49996 | [(3S)-3-[(tert-butoxycarbonyl)amino]-4-[(3-chlorobenzyl)amino]-4-oxobutyl](dimethyl)sulfonium iodide | C18H28ClIN2O3S | 详情 | 详情 | |
| (XII) | 49997 | tert-butyl (3S)-1-(3-chlorobenzyl)-2-oxopyrrolidinylcarbamate | C16H21ClN2O3 | 详情 | 详情 | |
| (XIII) | 49998 | (3S)-3-amino-1-(3-chlorobenzyl)-2-pyrrolidinone | C11H13ClN2O | 详情 | 详情 |