Triethylamine → N-((1R)-1-{5-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)phenyl]-3-fluoropyridin-2-yl}ethyl)-3,3-difluoro-1-hydroxycyclopentanecarboxamide

Participants

Reaction Steps

To a solution of the compound of Reference Example 4 (0.766 g, 2.18 mmol), (+)-3,3-difluoro-1-hydroxycyclopentanecarboxylic acid (0.454 g, 2.73 mmol), (1H-1,2,3-benzotriazol-1-yloxy)-[tris(dimethylamino)]phosphonium hexafluorophosphate (1.35 g, 3.06 mmol) in anhydrous dichloromethane (43 mL), was added triethylamine (0.553 g, 5.46 mmol). This reaction mixture was allowed to stir at ambient temperature for 1 hour. After the reaction was judged complete by LC/MS analysis, the volume of the reaction was reduced in vacuo. The residue was taken up in EtOAc, washed with water, 0.25 N HCl and saturated aqueous sodium bicarbonate solution. The organic extracts were dried over sodium sulfate, filtered, and concentrated. The crude residue was subjected to silica gel chromatography eluting with 0-50% EtOAc in hexanes to provide the title compound as a foam, which gave proton NMR spectra consistent with theory and a mass ion (ES+) of 499.2 for M+H+: 1H NMR (500 MHz, CDCl3) δ 8.13 (s, 1H), 7.96 (bd, NH), 7.34 (d, J=8.8 Hz, 1H), 7.26 (m, 2H), 5.41 (m, 1H), 4.342 (s, 3H), 2.82 (m, 1H), 2.46-2.25 (m, 4H), 1.92 (m, 1H), 1.45 (d, J=6.8 Hz, 3H).

Provenance & Evidence