HCID 67995196, compound → HCID 70651625, compound

Participants

Reaction Steps

To a solution of 7-acetyl-1-(3-(6-methoxy-1-oxoisoindolin-2-yl)-2-methylphenyl)-5H-pyridazino[4,5-b]indole-4-carboxamide (36.0 mg, 0.071 mmol) in tetrahydrofuran (8 mL) at 0° C. was added methylmagnesium bromide (0.119 mL, 0.356 mmol). The mixture was stirred at room temperature for 20 min. Additional methylmagnesium bromide (0.119 mL, 0.356 mmol) was added at 0° C. and the mixture was stirred at room temperature for another 20 min. The reaction was quenched with water (15 mL). The resulting mixture was extracted with ethyl acetate (3×30 mL). The combined extract was washed with brine (25 mL) and dried over anhydrous MgSO4. After solvent was removed under vacuum, the residue was purified by reverse phase HPLC. The correct fraction was concentrated under vacuum, basified with saturated NaHCO3 solution, and extracted with ethyl acetate (3×35 mL). The combined extract was washed with brine (30 mL) and dried over anhydrous MgSO4. Removal of solvent under vacuum provided the desired product (11.4 mg, 0.021 mmol, 30.1% yield) as a white solid. LCMS (M+H)+=522.20. 1H NMR (500 MHz, DMSO-d6) δ: 12.34 (s, 1H), 8.75 (s, 1H), 8.07 (s, 1H), 8.00 (s, 1H), 7.73 (d, J=6.9 Hz, 1H), 7.61-7.57 (m, 2H), 7.51 (d, J=6.4 Hz, 1H), 7.35-7.33 (m, 2H), 7.27-7.25 (m, 2H), 5.19 (s, 1H), 4.98 (d, J=16.9 Hz, 1H), 4.90 (d, J=16.9 Hz, 1H), 3.86 (s, 3H), 1.90 (s, 3H), 1.49 (s, 6H).

Provenance & Evidence