Triethylamine → HCID 86719482, compound

Participants

Reaction Steps

To a solution of 2-[(4-[[4-cyano-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]acetic acid (216 mg, 0.63 mmol, 1.5 eq) in dichloromethane (25 ml) was added EDAC.HCl (122 mg, 0.64 mmol, 1.5 eq), HOBt (86 mg, 0.64 mmol, 1.5 eq), triethylamine (128 mg, 1.26 mmol, 3 eq) and 1-[(5-fluoro-2,3-dihydro-1-benzofuran-2-yl)methyl]piperazine (100 mg, 0.42 mmol) at room temperature. The solution was stirred at room temperature overnight, diluted with dichloromethane (150 ml), and washed with water (80 ml). The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The crude material was purified by silica gel chromatography using 1-2% methanol in dichloromethane to elute. The product-containing fractions were combined and concentrated under vacuum to afford 4-[[4-(3-[4-[(5-fluoro-2,3-dihydro-1-benzofuran-2-yl)methyl]piperazin-1-yl]-2-oxopropoxy)cyclohexyl]amino]-2-(trifluoromethyl)benzonitrile as a white solid (0.18 g, 69%); (ES, m/z): [M+H]+ 561.20; 1H NMR (300 MHz, CDCl3): δ 7.56 (d, J=8.7 Hz, 1H), 6.81-6.92 (m, 3H), 6.64-6.71 (m, 2H), 5.13 (broad s, 1H), 4.29 (d, J=7.8 Hz, 1H), 4.21 (s, 2H), 3.67-3.77 (m, 3H), 3.34-3.47 (m, 3H), 2.92-2.99 (dd, J=˜8.1 Hz, ˜15.9 Hz, 1H), 2.51-2.89 (m, 5H), 2.15-2.25 (broadened d, J=9.9 Hz, 4H), 1.41-1.48 (m, 3H), 1.21-1.32 (m, 3H).

Provenance & Evidence