Methanol → 7-(morpholine-4-carbonyl)-3-(thiazol-4-yl)-9H-carbazole-1-carboxamide

Participants

Reaction Conditions

Reaction Steps

3-Bromo-7-(morpholine-4-carbonyl)-9H-carbazole-1-carboxamide (50 mg, 0.112 mmol, Example 144A), Pd(Ph3P)4 (7 mg, 6.06 nmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazole (37 mg, 0.175 mmol), aqueous Na2CO3 (0.15 mL, 0.300 mmol), MeOH (1 mL) and Toluene (2 mL) were combined in a 5 ml microwave vial. The vial was sealed, flushed with nitrogen and heated to 105° C. for 4 hours in an oil bath. Additional Pd(Ph3P)4 (20 mg, 15 nmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazole (65 mg, 0.308 mmol) and aqueous Na2CO3 (0.30 mL, 0.60 mmol) were added, the vial flushed with nitrogen again and heat to 105° C. for 5 additional hours. The reaction mixture was evaporated to dryness, suspended in water and the crude product was collected by filtration through a medium porosity glass frit. The crude was washed with water, then dissolved off the frit with DMSO and purified by prep HPLC. Product containing fractions were combined and concentrated in vacuum to give 19.4 mg 7-(morpholine-4-carbonyl)-3-(thiazol-4-yl)-9H-carbazole-1-carboxamide. MS (ESI) m/e+=407, m/e−=405, consistent with [M−H]− and [M+H]+. 1H NMR (CD3OD+CDCl3) δ ppm 9.11 (d, 1H, J=2.1), 8.91 (d, 1H, J=1.5), 8.57 (d, 1H, J=1.5), 8.26 (d, 1H, J=8.0), 7.96 (d, 1H, J=1.8), 7.72 (s, 1H), 7.32 (dd, 1H, J=7.9, 1.2), 3.90-3.50 (b, 8H). HPLC retention time 8.02 min. (Sunfire C18 3.5 μm, 4.6×150 mm column, 15 min gradient, 10-100% B, 1 mL/min. Solvent A: 5% CH3CN—95% H2O—0.1% TFA; Solvent B: 95% CH3CN—5% H2O—0.1% TFA).

Provenance & Evidence