Triethylamine → 4-(4-Dimethylcarbamoyl-3-fluoro-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (5-hydroxymethyl-pyridin-2-yl)-amide

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-(4-dimethylcarbamoyl-3-fluoro-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (143a) (381 mg, 1.02 mmol), 5-(tert-butyl-dimethyl-silanyloxymethyl)-pyridin-2-ylamine (22a) (365 mg, 1.53 mmol) and triethylamine (0.284 mL, 2.04 mmol) in 5 mL of DMF was added HATU (776 mg, 2.04 mmol). The mixture was stirred at 50° C. overnight, quenched with water, extracted with 3×EtOAc. The combined organic layer was washed with 2×H2O, dried with Na2SO4, concentrated and the resulting oil was purified by Biotage column chromatography with 50-100% EtOAc in hexanes to give a yellow solid (120 mg, 25% yield). 1H NMR (400 MHz, CDCl3) δ 8.76 (br. s., 1 H) 8.29 (d, J=8.59 Hz, 1 H) 8.21 (d, J=1.77 Hz, 1 H) 7.74 (dd, J=8.59, 2.27 Hz, 1 H) 7.35 (t, J=8.08 Hz, 1 H) 7.27 (s, 1 H) 7.11 (d, J=5.81 Hz, 1 H) 6.78 (dd, J=8.46, 2.40 Hz, 1 H) 6.68 (dd, J=10.61, 2.27 Hz, 1 H) 4.66 (s, 2 H) 3.11 (s, 3 H) 2.96 (s, 3 H) 2.88 (s, 2 H) 1.48 (s, 6 H); LCMS for C26H26FN3O5 m/z 480.20 (M+H).

Provenance & Evidence