Diisopropylethylamine → N-(4-(1H-Pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluorophenyl)-1-(4-fluorobenzyl)-2-oxo-1,2-dihydropyridine-3-carboxamide, hydrochloride salt

Participants

Reaction Conditions

Reaction Steps

A homogeneous solution of 1-(4-fluorobenzyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (0.051 g, 0.21 mmol, 1.0 eq), 4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluorobenzenamine (0.50 g, 0.21 mmol, 1.0 eq, Compound B of Example 132) and TBTU (0.086 g, 0.23 mmol, 1.1 eq) in DMF (1 mL) was treated with DIPEA (0.11 mL, 0.62 mmol, 3.0 eq) at room temperature. The reaction mixture was stirred for 12 h and quenched with 10% aqueous LiCl (15 mL). The resulting solution was extracted with ethyl acetate (4×40 mL). The combined organic extracts were washed with 10% aqueous LiCl (4×50 mL), dried (Na2SO4), filtered and the filtrate concentrated in vacuo. The residue was purified by flash chromatography (SiO2, eluting 0–2.5% MeOH in CHCl3) and the appropriate fractions were isolated and concentrated in vacuo. The free base was dissolved in THF, cooled to 0° C. and the homogeneous solution treated with anhydrous 4 N HCl in dioxane. The reaction mixture was warmed to room temperature, concentrated in vacuo and the residue triturated with diethyl ether. The solid was dried in vacuo to afford the title compound (0.062 g, 59%) as a HCl salt. 1H NMR (DMSO-d6) δ 12.43 (s, 1H), 12.27 (s, 1H), 8.50–8.52 (m, 1H), 8.35–8.37 (m, 1H), 8.25–8.27 (m, 1H), 8.05–8.0 (m, 1H), 7.43–7.55 (m, 5H), 7.20–7.24 (m, 2H), 6.71 (t, 1H, J=6.89 Hz), 6.65 (d, 1H, J=6.03 Hz), 6.43 (s, 1H), 5.32 (s, 2H); HRMS(ESI+): calcd: 473.1425, found: 473.1427.

Provenance & Evidence