Sodium Iodide → HCID 89923218, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-((2-chloro-5-cyano-3-(piperidin-4-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile, (Example 208D) (25 mg, 0.045 mmol), 2-bromo-2-methylpropanamide (37.5 mg, 0.226 mmol), sodium iodide (33.8 mg, 0.226 mmol) and Cs2CO3 (58.8 mg, 0.180 mmol) in CH3CN (1.2 mL) was heated at 120° C. for 2 h using microwave irradiation. The reaction mixture was diluted with DCM, filtered to remove insoluble material. The filtrate was concentrated. The residue was dissolved in DCE (1 mL). To this was added TFA (0.5 ml), anisole (0.1 ml, 0.918 mmol), and then heated at 50° C. for 3 h. Solvent was removed. The residue was applied onto a cartridge of Phenomenex Strata-X-C 33 um cation mixed-mode polymer. This was washed with methanol and product was eluted with large amount (3 CV) of mixture of 2 N solution of ammonia in methanol/DCM (1:1). Removal of the solvents left 23 mg material which was further purified via preparative LC/MS with the following conditions: Column: XBridge C18, 19×200 mm, 5-μm particles; Mobile Phase A: 5:95 methanol: water with 10-mM ammonium acetate; Mobile Phase B: 95:5 methanol: water with 10-mM ammonium acetate; Gradient: 50-100% B over 15 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to afford 2-(4-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-1-yl)-2-methylpropanamide (3.6 mg).

Provenance & Evidence