With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.115619-01-7,4-(4-Ethylpiperazin-1-yl)phenylamine,as a common compound, the synthetic route is as follows.
According to scheme I, to a 250-mL flash were added Compound Ia-1, i.e. 2,6-dichloro-3,5-dimethoxyaniline (10mmol) and AcOH (24ml), and added dropwisely under an ice-bath a solution of sodium nitrite (15mmol) in sulphuric acid (5.8ml) . The mixture was stirred at 25C until the solution became clear. The resulting dark yellow solution was poured into 150ml of an ice-water, and urea (6mmol) was added. The mixture was stirred and filtered. An aqueous solution of potassium iodide (15mmol) was added to the above dark-yellow solution. The mixture was heated at 85C for 2 hours, and cooled to room temperature. NaHSO3 (3.4 mmol) was added, and the mixture was stirred for 10 minutes. The resulting yellow solid was filtered, dried, and separated by column chromatography to produce Compound Ib-1 (8mmol). Compound Ib-1 (4 mmol), and Compound A-1, i.e. 4-piperidinone ethylene ketal (6 mmol) were dissolved in 50ml toluene, and palladium acetate (0.4 mmol), BINAP (0.48 mmol), and cesium carbonate (18 mmol) were added. The mixture was refluxed under the nitrogen protection for 3 days, and separated by column chromatography to produce Compound Ic-1. Compound Ic-1 (2.5 mmol) was dissolved in 10ml THF, and 10% aqueous H2SO4 solution (10ml) was added. The mixture was heated at 60C overnight, and separated by column chromatography to produce Compound Id-1. Compound Id-1 (1.0 mmol) was dissolved in 10ml dioxane, and DMF.DMA (6.0 mmol) and triethylamine (1.0 mmol) were added. The mixture was refluxed under the nitrogen protection for 2 days, and separated by thin layer chromatography to produce Compound Ie-1. Compound B-1, i.e., 1-fluoro-4-nitrobenzene (10 mmol) was dissolved in 20ml DMF, and C-1, i.e., N-ethylpiperazine (11 mmol), and potassium carbonate (30 mmol) were added. The mixture was reacted at 70C overnight. After cooling, the mixture was poured into ice-water, and filtered to produce Compound If-1. Compound If-1 (10 mmol) was dissolved in 20ml methanol or ethanol, and palladium/carbon (1mmol) was added. The mixture was hydrogenated at room temperature for 7 hours. The mixture was separated by column chromatography to produce Compound Ig-1. Compound Ig-1 (2.6 mmol) was dissolved in 10ml dioxane, and cyanoamine (2.73 mmol), and concentrated hydrochloric acid (3.9 mmol) were added. The mixture was stirred under reflux overnight to produce Compound Ih-1. Compound Ie-1 (1mmol) and Compound Ih-1 (1.05mmol) were dissolved in 8ml ethanol, and sodium acetate (2mmol) and triethylamine (1.05mmol) were added. The mixture was stirred under flux for 7 hours, ethanol concentrated, and water and dichloromethane were added. The organic phase was separated, dried over anhydrous sodium sulphate, and separated by thin layer chromatography to produce Compound I-1 (0.1mmol) in a yield of 10%.H1-NMR(deuterated MeOH) : delta8.11(s, 1H), delta7.56(d, 2H), delta6.99(d, 2H), delta6.72(s, 1H), delta4.25(s, 2H), delta3.93(s, 6H), delta3.56(t, 2H), delta3.23(m, 4H), delta2.92(t, 2H), delta2.8(m, 4H), delta2.64(m, 3H), delta1.2(t, 3H). ESI(+)m/z: 543, 115619-01-7
The synthetic route of 115619-01-7 has been constantly updated, and we look forward to future research findings.
Reference£º
Patent; Shanghai Allist Pharmaceutical and Medical Technology Corporations; KUANG, Rongren; (39 pag.)EP3466948; (2019); A1;,
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