Triethylamine → (R)-N-(1-(5-(5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)phenyl)-3-fluoropyridin-2-yl)ethyl)-4,4-difluoro-1-hydroxycyclohexanecarboxamide

Participants

Reaction Steps

A mixture of 4,4-difluoro-1-hydroxy-cyclohexanecarboxylic acid (324 mg, 1.8 mmol) and the compound of Reference Example 4 (632 mg, 1.8 mmol) was dissolved in 3.6 ml of degassed DMF. HOBT (58 mg, 0.43 mmol) and EDCI (449 mg, 2.34 mmol) were added, and the reaction mixture was made basic with triethylamine (182 mg, 1.8 mmol). After 1 hour at ambient temperature, 20 ml of water and 2 ml of 10% aqueous sodium bicarbonate solution were added and the mixture was extracted with EtOAc. The combined organic extracts were washed with water and brine, and dried over sodium sulfate, filtered, and concentrated. The crude material was subjected to silical gel chromatography eluting with 10 to 30% EtOAc in hexanes to provide the title compound as a white solid which gave a proton NMR spectrum consistent with theory and a mass ion (ES+) of 513.0 for M+H+: 1H NMR (500 MHz, CDCl3) δ 8.14 (s, 1H), 7.67 (d, J=7 Hz, 1H), 7.35 (d, J=10 Hz, 1 H), 7.28 (m, 2H), 5.41 (m, 1H), 4.36 (s, 3H), 2.88 (s, 1H), 2.12 (m, 6H), 1.76 (m, 2H), 1.44 (d, J=7 Hz, 3H).

Provenance & Evidence