4-Methylmorpholine → N-(4-(1-(4-methoxybenzyl)-3-(4-methylpiperazin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-3-oxo-2-(pyridin-2-yl)-2,3-dihydropyridazine-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

3-Oxo-2-(pyridin-2-yl)-2,3-dihydropyridazine-4-carboxylic acid (0.0282 g, 0.130 mmol; prepared as in Example 141, Steps A-C) was dissolved in 5 mL of CH2Cl2 and cooled to 0° C. HOBt (0.0351 g, 0.259 mmol), EDCI (0.0497 g, 0.259 mmol), and NMM (0.0333 ml, 0.303 mmol) were added and the reaction mixture was stirred under N2(g) for 15 minutes. 4-(1-(4-Methoxybenzyl)-3-(4-methylpiperazin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (0.020 g, 0.0432 mmol; prepared according to Example 86, Step A) in 2 mL of 1:1 CH2Cl2/DMF was added and the reaction was stirred at ambient temperature for 5 hours. The mixture was partitioned between EtOAc and aqueous NaHCO3. The organic layer washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography (Flash 5 g) eluting with 3% MeOH/CH2Cl2 to afford the desired product as yellow semi-solid. Yield: 25.8 mg, 86%. LRMS (APCI pos) m/e 662 (M+H).

Provenance & Evidence