4-Chloro-6-nitroquinoline → N-[4-(2-Amino-6-methylpyrimidin-4-ylamino)phenyl]-4-(6-nitroquinolin-4-ylamino)benzamide hydrochloride

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Reaction Steps

To a solution of amine E5 (304 mg, 0.82 mmol) in dry MeOH (30 mL) were sequentially added 4-chloro-6-nitroquinoline (F1) (171 mg, 0.82 mmol) and c.HCl (1-2 drops), and the resulting mixture was refluxed for ˜12 h. MS and TLC analysis after this time showed some F1 was still present in the reaction mixture, so further aliquots of E5 (171 mg, 0.82 mmol) and c.HCl (1-2 drops) were added at 12 h and 24 h. Solvent was then removed from the reaction mixture, and the resulting residue dissolved in MeOH, and then re-concentrated under reduced pressure. The residue was subjected to a further MeOH azeotrope cycle, and the resulting residue was then reprecipitated from MeOH:Et2O to afford Cpd. H as an amorphous yellow solid (383 mg, 86%). 1H NMR (400 MHz, DMSO): 2.28 [s, 3H, ArCH3], 6.18 [br s, 1H, ArH], 7.11 [d, J=6.59 Hz, 1H, ArH], 7.65 Hz [d, J=8.52 Hz, 2H, ArH], 7.81 [m, 5H, ArH & ArNH2], 8.17 [d, J=8.52 Hz, 2H, ArH], 8.25 [d, J=9.30 Hz, 1H, ArH], 8.69 [m, 2H, ArH], 9.77 [s, 1H, ArH], 10.42 [s, 1H, ArH], 10.62 [br s, 1H, ArNHAr], 11.20 [v br s, 1H, ArNHAr], 12.63 [v br s, 1H, ArC(O)NH]. LCMS (APCI+): 508 (100%). HPLC: 98.5%.

Provenance & Evidence