Formaldehyde → Trifluoroacetic acid

Participants

Reaction Steps

To a mixture of N-(3-fluoro-4-(6-methoxy-7-(piperidin-4-ylmethoxy)quinolin-4-yloxy)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide TFA salt (22 mg, 0.030 mmol) and NaBH(OAc)3 (40 mg) in CH2Cl2 was added HCHO (0.1 mL of 33% solution) and the reaction mixture was stirred at rt for 6 h. Direct purification by preparative HPLC afforded the desired product as a white TFA salt solid (11 mg, 50%). 1H NMR (CDCl3) δ 12.16 (s, 1H), 8.77 (dd, 1H, J=7.7, 2.2 Hz), 8.55 (d, 1H, J=6.1 Hz), 8.08 (d, 1H, J=1.6 Hz), 8.06 (dd, 1H, J= 12.1, 1.6 Hz), 7.64-7.27 (m, 8H), 6.71 (d, 1H, J=6.6 Hz), 6.66 (t, 1H, J=6.6 Hz), 4.27 (d, 2H, J=5.5 Hz), 4.07 (s, 3H), 3.66 (d, 2H, J=12.1 Hz), 2.81 (s, 3H), 2.87-1.97 (m, 7H); MS(ESI+) m/z 627.4 (M+H)+.

Provenance & Evidence