1-Hydroxybenzotriazole → N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide

Participants

Reaction Steps

A round-bottomed flask was charged with 3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)benzenamine (Example 6, Step A, 1.00 g, 2.59 mmol), 2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acid (0.728 g, 3.11 mmol, example 104, step C), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.596 g, 3.11 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (0.420 g, 3.11 mmol), N-ethyl-N-isopropylpropan-2-amine (0.669 g, 5.178 mmol) and DMF (50 mL). The reaction mixture was stirred at room temperature until the starting material had been consumed (overnight). Then the reaction was partitioned between EtOAc (200 mL) and H2O (200 mL). The phases were separated and the aqueous phase was re-extracted with EtOAc (3×200 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude product. The crude product was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 100/1 to 10/1, v/v) to afford product (1.34 g, 85.8%). LRMS (APCI pos): >99% purity, 254 nm, m/e 603 (M+1). 1H NMR (400 MHz, CDCl3) δ 11.85 (s, 1H), 8.43 (m, 2H), 8.24 (d, 1H), 7.96 (dd, 1H), 7.77 (s, 1H), 7.60 (m, 2H), 7.40 (m, 1H), 7.21-7.28 (m, 3H), 6.48 (m, 1H).

Provenance & Evidence