Dimethylamine → N-(4-(2-(4-(Dimethylamino)cyclohexyl)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-(4-oxocyclohexyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (Example 162, Step C, 3.2 mg, 0.0056 mmol), dimethylamine (1.3 mg, 0.028 mmol), NaBH(OAc)3 (3.6 mg, 0.017 mmol) and CH2Cl2 (2 mL). The reaction mixture was stirred at room temperature until the starting material had been consumed (overnight). Then the reaction was partitioned between EtOAc (30 mL) and H2O (30 mL). The phases were separated and the aqueous phase was re-extracted with EtOAc (3×30 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 50/1 to 10/1, v/v) to afford product (2.1 mg, 62%). LRMS (APCI pos): m/e 602 (M+1). 1H NMR (400 MHz, CDCl3) δ 11.82 (s, 1H), 8.43 (d, 1H), 8.41 (d, 1H), 8.24 (d, 1H), 7.95 (dd, 1H), 7.60 (m, 2H), 7.38 (m, 1H), 7.21-7.32 (m, 4H), 6.45 (d, 1H), 3.22 (m, 1H), 2.30 (s, 6H), 2.22 (m, 1H), 1.55-1.94 (m, 8H).

Provenance & Evidence