Acetaldehyde → N-(4-(2-(1-Ethylpiperidin-4-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide

Participants

Reaction Steps

A round-bottomed flask was charged with N-(3-fluoro-4-(2-(piperidin-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (Example 154, Step C, 43.4 mg, 0.0776 mmol), acetaldehyde (17.1 mg, 0.388 mmol), NaBH(OAc)3 (82 mg, 0.388 mmol) and THF (10 mL). The reaction mixture was stirred at room temperature until the starting material had been consumed (overnight). Then the reaction was partitioned between EtOAc (100 mL) and H2O (100 mL). The phases were separated and the aqueous phase was re-extracted with EtOAc (3×100 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 crude product. The crude product was further purified with preparative HPLC to afford product (1.3 mg, 2.14%). LRMS (APCI neg): >97% purity, 254 nm, m/e 587 (M). 1H NMR (400 MHz, CD3OD) δ 8.41 (d, 1H), 8.36 (d, 1H), 8.31 (d, 1H), 8.03 (dd, 1H), 7.67 (m, 2H), 7.49 (m, 1H), 7.39 (t, 1H), 7.29 (m, 3H), 6.62 (d, 1H), 2.60 (q, 2H), 2.32 (m, 2H), 2.19 (m, 2H), 1.94 (m, 1H), 1.18 (t, 3H), 0.90 (m, 4H).

Provenance & Evidence