Trifluoroacetic acid → N-(4-(3-(4-(dimethylamino)piperidin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

A 50 mL round-bottomed flask was charged with N-(4-(1-(4-methoxybenzyl)-3-(4-(dimethylamino)piperidin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (33.1 mg, 0.0468 mmol) and CF3COOH (5 mL). The reaction mixture was stirred at 80° C. overnight. Then the solvent was removed and the residue was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1, v/v) to afford the product (18.3 mg, 66.6%). LRMS (APCI pos): >99% purity, 254 nm, m/e 587 (M+1). 1H NMR (400 MHz, CDCl3) δ 11.83 (s, 1H), 10.80 (s, 1H), 8.42 (d, 1H), 8.28 (d, 1H), 8.24 (m, 1H), 7.98 (dd, 1H), 7.60 (m, 2H), 7.41 (d, 1H), 7.21-7.33 (m, 3H), 6.20 (d, 1H), 4.12 (m, 2H), 2.91 (m, 2H), 2.63 (m, 1H), 2.47 (s, 6H), 2.01 (m, 2H), 1.80 (m, 2H).

Provenance & Evidence