Hydrochloric Acid → N-(2-aminophenyl)-4-[3-[(4-chlorophenyl)amino]-2-(4-methylpiperazin-1-yl)-3-oxopropyl]benzamide

Participants

Reaction Steps

The compound from Step A above (68.9 mg, 0.166 mmol) was dissolved in THF (1 mL) and methanol (0.2 mL). To this solution, was added LiOH solution in water (22.3 mg, 0.931 mmol/0.4 mL H2O). The resulting solution was stirred at room temperature for 8 hours to give 100% conversion, then neutralized with HCl (conc., 77 μL). The solvent was evaporated to afford white solid, which included the acid and small amount of LiCl. The white solid (66.5 mg), benzene-1,2-diamine (26.9 mg, 0.249 mmol), EDCI (47.7 mg, 0.249 mmol) and HOBt (33.6 mg, 0.249 mmol) were dissolved in 0.6 mL DMF. The resulting solution was stirred at room temperature for 4 hours. The reaction mixture was diluted with 20 mL of CH2Cl2. The organic solution was washed with 10 mL of NaHCO3 (sat'd), 10 mL of H2O, and 10 mL of brine successively, dried over MgSO4. The filtrate was concentrated to give crude product which was purified by reversed phase HPLC to give the desired product. 1H NMR (600 MHz, (CD3)2CO) δ 9.37 (d, J=11.1 Hz, 1H), 8.93 (br s, 1H), 7.81 (dm, 2H, J=8.0 Hz, 2H), 7.50-7.56 (m, 2H), 7.28-7.36 (m, 2H), 7.12-7.20 (m, 3H), 6.86 (tm, J=7.3 Hz, 1H), 6.73 (dd, J=1.1 and 8.0 Hz, 1H), 6.54 (tm, J=7.3 Hz, 1H), 3.46-3.54 (m, 1H), 3.12-3.20 (m, 1H), 2.92 (dd, J=5.7 and 13.6 Hz, 1H), 2.62-2.84 (m, 4H), 2.14-2.36 (m, 4H), 1.92 (s, 3H). MS cal'd 492.2 (MH+), exp 492.2 (MH+).

Provenance & Evidence