Pyridine → N-[4-(7-azabicyclo[2.2.1]heptan-7-yl)-2-(3-dimethylaminoprop-1-ynyl)phenyl]-4-oxo-5-(trifluoromethyl)-1H-quinoline-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-oxo-5-(trifluoromethyl)-1H-quinoline-3-carboxylic acid 17 (19 mg, 0.07 mmol) and 4-(7-azabicyclo[2.2.1]heptan-7-yl)-2-(3-dimethylaminoprop-1-ynyl)aniline 27 (20 mg, 0.07 mmol) in 2-methyltetrahydrofuran (190.9 μL) was added T3P (118 mg, 0.19 mmol) and pyridine (12 mg, 12 μL, 0.15 mmol). The reaction was heated at 100° C. for 30 min under microwave irradiation. The reaction was diluted with EtOAc and quenched with saturated aqueous NaHCO3 (50 mL). The layers were separated, and the aqueous layer was extracted twice with EtOAc. The combined organics were washed once with water, dried over Na2SO4, filtered and concentrated. The residue was purified by reverse phase HPLC (0-99% CH3CN/0.05% TFA) to give N-[4-(7-azabicyclo[2.2.1]heptan-7-yl)-2-(3-dimethylaminoprop-1-ynyl)phenyl]-4-oxo-5-(trifluoromethyl)-1H-quinoline-3-carboxamide (8 mg, 17% yield). LC/MS m/z 509.7 [M+H]+, retention time 1.06 min (RP-C18, 10-99% CH3CN/0.05% TFA over 3 min). 1H NMR (400.0 MHz, DMSO-d6) δ 13.23 (d, J=6.8 Hz, 1H), 12.40 (s, 1H), 10.31 (s, 1H), 8.96 (d, J=6.6 Hz, 1H), 8.40 (d, J=9.0 Hz, 1H), 8.08-8.06 (m, H), 8.07 (dd, J=1.5 Hz, 8.1 Hz, 1H), 8.00-7.95 (m, 2H), 7.15-7.09 (m, 2H), 4.49 (s, 2H), 4.29 (s, 2H), 2.94 (s, 6H), 1.67 (d, J=7.2 Hz, 4H), 1.44 (d, J=7.0 Hz, 4H).

Provenance & Evidence