Trifluoroacetic acid → 3-(1-methyl-1H-indazol-5-yl)-7-(piperazin-1-yl)-9H-carbazole-1-carboxamide

Participants

Reaction Steps

The crude product from Example 413B [168 mg, contains ˜0.16 mmol tert-butyl 4-(8-carbamoyl-6-(1-methyl-1H-indazol-5-yl)-9H-carbazol-2-yl)piperazine-1-carboxylate was suspended in ClCH2CH2Cl (20 ml). Addition of TFA (2 ml, 26.0 mmol) resulted in complete dissolution. The reaction mixture was stirred at room temperature for 2.5 hours, then evaporated to dryness. The product was purified by prep HPLC to give 62.6 mg 3-(1-methyl-1H-indazol-5-yl)-7-(piperazin-1-yl)-9H-carbazole-1-carboxamide. The “free base product” was suspended in MeOH. Addition of 1.0 equiv. HCl (147 ul of a 1.00 M aq. solution) resulted in complete dissolution. Evaporate to dryness gave 67.8 mg 3-(1-methyl-1H-indazol-5-yl)-7-(piperazin-1-yl)-9H-carbazole-1-carboxamide as its mono-HCl salt. MS (ESI) m/e+=425. HPLC retention time 5.82 min. (Sunfire C18 3.5 μm, 3.0×150 mm column, 15 min gradient, 10-100% B, 0.5 mL/min. Solvent A: 5% CH3CN—95% H2O—0.1% TFA; Solvent B: 95% CH3CN—5% H2O—0.1% TFA), then isocratic at 100% B. 1H NMR (CD3OD) δ ppm 8.46 (d, 1H, J=1.5), 8.17 (d, 1H, J=1.7), 8.13 (b, 1H), 8.11-8.07 (m, 2H), 7.91 (dd, 1H, J=1.8, 8.8), 7.67 (d, 1H, J=8.8), 7.23 (d, 1H, J=2.0), 7.03 (dd, 1H, J=8.5, 2.0), 4.12 (s, 3H), 3.56-3.52 (m, 4H), 3.47-3.43 (m, 4H).

Provenance & Evidence