Methylacrylamide → 3-(4-((6-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)piperazin-1-yl)-N-methylpropanamide

Participants

Reaction Conditions

Reaction Steps

A stirred suspension of compound 49 (100 mg, 0.19 mmol, scheme 15) and N-methylacrylamide (1.5 mL) in acetonitrile (20 mL) was heated to 110° C. overnight in a sealed flask. The reaction mixture was cooled to RT, concentrated, and the residue was purified twice by Biotage (SNAP 25 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 5/95 to 15/85 over 20 CV and SiliaFlash 12 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 5/95 to 15/85 over 20 CV, then 15/85 over 5 CV), to afford the title compound 81 (50 mg, 0.08 mmol, 43% yield) as a white sticky solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.72 (s, 1H), 8.54 (bd, J=1.4 Hz, 1H), 8.52 (d, J=5.5 Hz, 1H), 8.33 (s, 1H), 8.24 (d, J=8.0 Hz, 1H), 7.85 (dd, J=8.1, 2.1 Hz, 1H), 7.85-7.77 (m, 1H), 7.73 (dd, J=13.6, 2.4 Hz, 1H), 7.38 (t, J=9.1 Hz, 1H), 7.20 (bd, J=8.9 Hz, 1H), 6.64 (bd, J=5.4 Hz, 1H), 6.57 (bd, J=2.5 Hz, 1H), 3.54 (s, 2H), 2.59-2.51 (m, 6H), 2.47-2.11 (m, 10H), 0.72-0.58 (m, 2H), 0.50-0.36 (m, 2H). MS 604.4 (m/z): (M+H).

Provenance & Evidence