Potassium Carbonate → HCID 59375153, compound

Participants

Reaction Steps

A mixture of 7-hydroxy-4-(2-methyl-3-(6-methyl-1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide (Example 40-2, 30 mg, 0.065 mmol) and potassium carbonate (36 mg, 0.260 mmol) in DMF (1.0 mL) was stirred at rt for 30 min, then was treated with 2-(bromomethyl)oxirane (27 mg, 0.195 mmol). The resulting mixture was heated at 90° C. for 3.5 h, cooled to rt and filtered. The filtrate was treated with methanol, stirred at rt for 2 h, then was then heated at 90° C. for 1 h. The mixture was concentrated under vacuum and purified by preparative HPLC to provide 7-(2-hydroxy-3-methoxypropoxy)-4-(2-methyl-3-(6-methyl-1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide (Example 44-5, 4.7 mg, 13%). 1H NMR (400 MHz, methanol-d4) δ 7.83 (1H, d, J=7.9 Hz), 7.72 (1H, d, J=0.7 Hz), 7.46-7.52 (4H, m), 7.38-7.45 (1H, m), 7.04-7.12 (2H, m), 6.99 (1H, d, J=8.8 Hz), 6.70 (1H, dd, J=8.7, 2.3 Hz), 4.86 (2H, d, J=1.8 Hz), 4.03-4.22 (3H, m), 3.53-3.65 (2H, m), 3.42 (3H, s), 2.50 (3H, s), 1.93 (3H, s). Mass spectrum m/z 550.1 (M+H)+. Also isolated was 7-(3-(dimethylamino)-2-hydroxypropoxy)-4-(2-methyl-3-(6-methyl-1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide (Example 44-6, 2.0 mg, 5%). Mass spectrum m/z 563.1 (M+H)+.

Provenance & Evidence