2,4,6-Trimethylpyridine → HCID 59559902, compound

Participants

Reaction Steps

To a solution of 2-hydroxymethyl-4-(4-methanesulfonyl-phenoxy)-2-methyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide (227) (62 mg, 0.140 mmol) and 2,4,6-collidine (0.0359 mL, 0.271 mmol) in dry CH2Cl2 was added trifluoromethanesulfonic acid anhydride (0.0365 mL, 0.217 mmol) at 0° C. The mixture was stirred at 0° C. to room temperature for 1 hr. TLC indicated that the reaction was complete. The reaction was quenched with 0.5 N aqueous HCl, extracted with 3×CHCl3, dried over Na2SO4, and concentrated. The residue was dissolved in anhydrous CH2Cl2 (3 mL), and TBAF (1 mL, 1 M in THF) was added. The resulting mixture was stirred at room temperature for 1.5 hr, quenched with H2O, and extracted with 3×CHCl3. The combined organic layer was dried over Na2SO4, concentrated, and purified by column chromatography eluting with 50-65% EtOAc in hexanes to give a white solid (18 mg, 28% yield). 1H NMR (400 MHz, CDCl3) δ 8.55 (s, 1 H) 7.84-7.96 (m, 2 H) 7.25-7.31 (m, 2 H) 7.02-7.15 (m, 3 H) 6.72-6.83 (m, 1 H) 4.26-4.54 (m, 2 H) 3.79 (s, 3 H) 3.20 (d, J=16.67 Hz, 1 H) 3.08 (s, 3 H) 2.89 (dd, J=16.67, 1.77 Hz, 1 H) 1.52 (s, 3 H); LCMS for C22H22FN3O5S m/z 460.00 (M+H+).

Provenance & Evidence