Diisopropylethylamine → (S)-Methyl 6-(((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)carbamoyl)nicotinate

Participants

Reaction Steps

To a solution of (S)-(3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methanamine hydrochloride (17.0 g, 49.9 mmol, Intermediate 6) in DMF (166 mL, Aldrich) was added 5-(methoxycarbonyl)pyridine-2-carboxylic acid (9.94 g, 54.9 mmol, Oakwood Products, Inc.), HATU (20.87 g, 54.9 mmol, Accela ChemBio, Inc.), and DIPEA (18.23 mL, 105 mmol, EMD Biosciences, Inc.). The resulting mixture was then stirred at room temperature for 18 h. Water (400 mL) was then added and the mixture was extracted with EtOAc (2×200 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. The residue was then dissolved in MeOH (500 mL) and silica gel was added. The mixture was concentrated and dried in vacuo. The solid mixture was purified by silica gel flash column chromatography using ISCO instrument (solid loading, 0-100% EtOAc/hexane) to give the title compound as a white solid. MS (ESI, positive ion) m/z: 468 (M+H).

Provenance & Evidence