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【结 构 式】 
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【分子编号】25440 【品名】3-(4-morpholinyl)-1-propanamine 【CA登记号】123-00-2 |
【 分 子 式 】C7H16N2O 【 分 子 量 】144.21692 【元素组成】C 58.3% H 11.18% N 19.42% O 11.09% |
合成路线1
该中间体在本合成路线中的序号：(IX)Condensation of pyruvic aldehyde dimethyl acetal (I) with dimethylformamide dimehylacetal provided ketoenamine (II). This was cyclized with guanidine to afford aminopyrimidine (III). Then, hydrolysis of the dimethyl acetal of (III) with 3 M HCl yielded aldehyde (IV). 4-Fluorobenzaldehyde (V) was condensed with thiocresol (VI) and formamide in refluxing toluene to give 4-fluorophenyl-tolylthiomethyl formamide (VII), which was dehydrated to isocyanide (VIII) with POCl3 and Et3N at -30 C. Finally, imine (X), (obtained from pyrimidine aldehyde (IV) and 4-(3-aminopropyl)morpholine (IX)), was condensed with isocyanide (VIII) in the presence of 1,5,7-triazabicyclo[4.4.0]dec-5-ene to furnish the title imidazole.
| 【1】 Adams, J.L.; Boehm, J.C.; Kassis, S.; Gorycki, P.D.; Webb, E.F.; Hall, R.; Sorenson, M.; Lee, J.C.; Ayrton, A.; Griswold, D.E.; Gallagher, T.F.; Pyrimidinylimidazole inhibitors of CSBP/p38 kinase demonstrating decreased inhibition of hepatic cytochrome P450 enzymes. Bioorg Med Chem Lett 1998, 8, 22, 3111. |
| 【2】 Adams, J.L.; Sheldrake, P.W.; Gallagher, T.F.; Garigipati, R.S.; Bender, P.E.; Boehm, J.C. (SmithKline Beecham plc); Tri-substd. imidazoles having multiple therapeutic properties. EP 0708768; WO 9502591 . |
| 【3】 Garigipati, R.S.; Adams, J.L.; Boehm, J.C. (SmithKline Beecham Corp.); Pyridyl imidazole cpds. and compsns.. US 5670527 . |
| 【4】 Adams, J.L.; Boehm, J.C.; Imidazole cpds., use and process of making. US 5593991 . |
| 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) | 25433 | 1,1-dimethoxyacetone | 6342-56-9 | C5H10O3 | 详情 | 详情 |
| (II) | 25434 | (E)-4-(dimethylamino)-1,1-dimethoxy-3-buten-2-one | C8H15NO3 | 详情 | 详情 | |
| (III) | 25435 | 4-(dimethoxymethyl)-2-pyrimidinylamine | C7H11N3O2 | 详情 | 详情 | |
| (IV) | 25436 | 2-amino-4-pyrimidinecarbaldehyde | C5H5N3O | 详情 | 详情 | |
| (V) | 12337 | 4-fluorobenzaldehyde | 459-57-4 | C7H5FO | 详情 | 详情 |
| (VI) | 25437 | 4-methylphenylhydrosulfide | 106-45-6 | C7H8S | 详情 | 详情 |
| (VII) | 25438 | (4-fluorophenyl)[(4-methylphenyl)sulfanyl]methylformamide | C15H14FNOS | 详情 | 详情 | |
| (VIII) | 25439 | 4-Fluoro-alpha-(4-methylphenylsulfanyl)benzyl isocyanide | C15H12FNS | 详情 | 详情 | |
| (IX) | 25440 | 3-(4-morpholinyl)-1-propanamine | 123-00-2 | C7H16N2O | 详情 | 详情 |
| (X) | 25441 | 4-([[3-(4-morpholinyl)propyl]imino]methyl)-2-pyrimidinamine | C12H19N5O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)N-(3-Aminopropyl)morpholine (I) was protected as the N-Boc derivative (II) and then quaternized with iodomethane to produce the ammonium salt (III). Subsequent acid deprotection of (III) gave amine (IV). Treatment of 2,6-dimethyl-4-pyrone (V) with Lawesson’s reagent in toluene yielded the thiono derivative (VI), which was coupled with amine (IV) to afford the pyridine thione (VII).
| 【1】 Singh, J.; et al.; A practical synthesis of an anti-methicillin resistant Staphylococcus aureus cephalosporin BMS-247243. Org Process Res Dev 2000, 4, 6, 488. |
| 【2】 Kim, O.; et al.; Discovery, synthesis and SAR of BMS-247243, a novel cephalosporin active against methicillin-resistant Staphylococcus aureus (MRSA) and susceptible Staphylococcus aureus (MSSA). 40th Intersci Conf Antimicrob Agents Chemother (Sept 17 2000, Toronto) 2000, Abst F-1062. |
| 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) | 25440 | 3-(4-morpholinyl)-1-propanamine | 123-00-2 | C7H16N2O | 详情 | 详情 |
| (II) | 46007 | tert-butyl 3-(4-morpholinyl)propylcarbamate | C12H24N2O3 | 详情 | 详情 | |
| (III) | 46008 | 4-[3-[(tert-butoxycarbonyl)amino]propyl]-4-methylmorpholin-4-ium iodide | C13H27IN2O3 | 详情 | 详情 | |
| (IV) | 46009 | 4-(3-aminopropyl)-4-methylmorpholin-4-ium iodide | C8H19IN2O | 详情 | 详情 | |
| (V) | 46010 | 2,6-dimethyl-4H-pyran-4-one | 1004-36-0 | C7H8O2 | 详情 | 详情 |
| (VI) | 46011 | 2,6-dimethyl-4H-pyran-4-thione | C7H8OS | 详情 | 详情 | |
| (VII) | 46012 | 4-[3-[2,6-dimethyl-4-thioxo-1(4H)-pyridinyl]propyl]-4-methylmorpholin-4-ium iodide | C15H25IN2OS | 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 bis-imide was synthesized by condensation of 3,4,9,10-perylenetetracarboxylic acid dianhydride (I) with N-(3-aminopropyl)morpholine (II) in hot n-butanol.
| 【1】 Kerwin, S.M.; et al.; G-quadruplex DNA binding selectivity of perylenetetracarboxylic acid diimides is PH dependent and mediated by ligand aggregation. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 142. |
| 【2】 Salazar, M.; Kerwin, S.M.; Hurley, L.H.; Fedoroff, O.Y. (University of Texas System); Inhibition of human telomerase by a G-quadruplex-interaction cpd.. US 6156763; WO 9940087 . |