Hydrochloric Acid → 4-(3-(isoquinolin-1-ylamino)-2-methylphenyl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide

Participants

Reaction Conditions

Reaction Steps

A suspension of 4-(3-amino-2-methylphenyl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide (Example 3-2, 35 mg, 0.079 mmol) and 1-chloroisoquinoline (19.45 mg, 0.119 mmol) in isopropanol (0.5 mL) was treated with 4M hydrogen chloride in 1,4-dioxane (3 drops) and the mixture was heated in a sealed tube by microwave irradiation at 140° C. for 45 min. Additional 4 M hydrogen chloride in 1,4-dioxane (1 drop) was added and the mixture was again heated in a sealed tube by microwave irradiation at 140° C. for 60 min. The mixture was concentrated and the residue was purified by preparative HPLC. The appropriate effluent fractions were concentrated and the residue was partitioned between NaHCO3 (aq) and EtOAc, and the aqueous phase was extracted twice more with EtOAc. The combined organic phases were dried and concentrated to provide 4-(3-(isoquinolin-1-ylamino)-2-methylphenyl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide as a white solid (16 mg, 32%). 1H NMR (400 MHz, methanol-d4) δ 8.28 (1H, d, J=8.3 Hz), 7.91 (1H, d, J=7.8 Hz), 7.72 (1H, d, J=6.1 Hz), 7.66 (1H, d, J=8.3 Hz), 7.56-7.61 (2H, m), 7.48 (1H, ddd, J=8.0, 7.2, 0.8 Hz), 7.44 (1H, d, J=7.5 Hz), 7.34 (1H, t, J=7.8 Hz), 7.22 (1H, d, J=8.0 Hz), 7.14 (1H, d, J=6.7 Hz), 7.06 (1H, d, J=7.8 Hz), 6.97 (1H, d, J=6.1 Hz), 6.94 (1H, dd, J=8.2, 1.5 Hz), 3.71 (2H, br. s.), 3.42 (2H, br. s.), 2.45 (2H, br. s.), 2.32 (2H, br. s.), 2.23 (3H, s), 1.81 (3H, s). Mass spectrum m/z 569.4 (M+H)+.

Provenance & Evidence