4-Piperidinoaniline

• Amino acid arylamides
• Selective interleukin-2 inducible T-cell inhibitors
• Antimalarial drugs
• Aglycoristocetin derivatives for anti-influenza virus activity
• IRAK-4 inhibitors
• 9-Aminoacridines with antiprion activity

6574-15-8

2359-60-6

The general procedure for the synthesis of 1-(4-nitrophenyl)piperidine was as follows: first, 4-fluoronitrobenzene (323 mg, 2.3 mmol) was dissolved in DMSO (5 mL), followed by the addition of potassium carbonate (475 mg, 3.5 mmol) and piperidine (460 μL, 4.6 mmol). The reaction mixture was stirred at 90 °C for 9 hours. After completion of the reaction, water was added to the reaction solution and extracted twice with ethyl acetate. The organic layers were combined and washed twice with saturated aqueous NaCl followed by drying with anhydrous Na2CO3. The solvent was evaporated under reduced pressure to give 1-(4-nitrophenyl)piperidine (Y197, yield: 472 mg, 100%). Next, Y197 (472 mg) was dissolved in ethyl acetate (20 mL), Pd/C (186 mg) was added, and the reaction was stirred for 3 h at room temperature under hydrogen atmosphere. Upon completion of the reaction, the reaction mixture was filtered through diatomaceous earth and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: chloroform:methanol = 40:1) to afford 1-(4-aminophenyl)piperidine (Y222, yield: 394 mg, quantitative). Finally, Y491 (80 mg, 0.18 mmol) was dissolved in dichloromethane (2 mL), Y222 (100 mg, 0.58 mmol) was added and stirred at room temperature for 5 hours. After the reaction was completed, the solvent was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (eluent: chloroform:methanol = 35:1) to afford the target product 1-(p-aminophenyl)piperidine (yield: 68 mg, 64%). The structure of the product was confirmed by 1H NMR, 13C NMR and HRMS.1H NMR (500 MHz, CDCl3) δ 8.40 (s, 1H), 8.0 (d, 1H, J = 8.0 Hz), 7.70 (d, 1H, J = 8.5 Hz), 7.52 (dd, 1H, J = 8.0, 7.5 Hz), 6.92 (dd, 2H, J = 9.0, 3.5 Hz), 6.92 (dd, 2H, J = 9.0, 3.5 Hz). = 9.0, 3.5 Hz), 6.77 (dd, 2H, J = 9.0, 6.5 Hz), 5.33 (t, 1H, J = 6.0 Hz), 4.07 (bs, 2H), 3.11-3.09 (m, 4H), 2.79-2.64 (m, 4H), 1.69-1.53 (m, 10H), 1.43 (s, 9H), 1.09-1.01 (m, 9H) 1.09-1.01 (m, 2H).13C NMR (125 MHz, CDCl3) δ 154.9, 141.6, 140.8, 131.4, 130.9, 129.8, 125.8, 125.7, 79.7, 77.4, 48.7, 36.6, 29.6, 28.6, 25.7, 24.2.HRMS ( FAB-) m/z: [M-H]- calculated value C28H39N4O6S2, 591.2311; measured value, 591.2324.