Trifluoroacetic acid → N-(3-fluoro-4-(3-(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

A round-bottomed flask was charged with N-(4-(1-(4-methoxybenzyl)-3-(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (13.8 mg, 0.0200 mmol) and CF3COOH (5 mL). The reaction mixture was stirred at 80° C. overnight. 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 give product, which was further purified by preparative HPLC to afford the desired product (2.1 mg, 13.2%). LRMS (APCI pos): >99% purity, 254 nm, m/e 571 (M+1). 1H NMR (400 MHz, CD3OD δ 11.92 (s, 1H), 8.34 (d, 1H), 8.29 (d, 1H), 8.21 (d, 1H), 8.03 (d, 1H), 7.65 (m, 2H), 7.48 (d, 1H), 7.41 (m, 1H), 7.26 (m, 2H), 6.26 (d, 1H), 3.74 (d, 2H), 3.57 (m, 2H), 3.08-3.38 (m, 6H).

Provenance & Evidence