Pyridine → Ethyl 1-(6-{2-[(4-methoxyphenyl)ethynyl]phenyl}pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

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Reaction Steps

To a cooled (0° C.) solution of the title compound from Example 1 Step B (374 mg, 0.991 mmol) and pyridine (0.241 mL, 2.97 mmol) in DCM (5 mL) was added trifluoromethanesulfonic anhydride (0.251 mL, 1.487 mmol). The cooling bath was immediately removed, and the reaction mixture was allowed to stir at ambient temperature. After 45 min, the reaction mixture was poured into water and extracted with DCM. The layers were separated and the organic phase was concentrated in vacuo, yielding material that was sufficiently pure for use in the next step: LCMS m/z 510.0 [M+H]+. To a flask containing the unpurified triflate were added copper (I) iodide (56.1 mg, 0.294 mmol), trans-dichlorobis(triphenylphosphine) palladium (II) (68.9 mg, 0.098 mmol), tetrabutylammonium iodide (1.088 g, 2.94 mmol), and 4-methoxyphenylacetylene (195 mg, 1.47 mmol). The flask with flushed with nitrogen, and acetonitrile (5 mL) was added. The mixture was degassed with nitrogen, triethylamine (1.00 mL, 7.17 mmol) was added, and the resulting mixture was stirred at ambient temperature. After 20 h, the reaction mixture was concentrated in vacuo. Purification by flash chromatography on silica gel (0 to 30% EtOAc in hexanes, then 30 to 100% EtOAc in hexanes) provided the title compound: LCMS m/z 492.1 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 8.32 (d, J=8.0 Hz, 1H), 8.14 (s, 1H), 7.99 (t, J=8.0 Hz, 1H), 7.89 (d, J=7.5 Hz, 1H), 7.65-7.63 (m, 2H), 7.47-7.39 (m, 2H), 7.33 (d, J=8.5 Hz, 2H), 6.86 (d, J=8.5 Hz, 2H), 4.38 (q, J=7.0 Hz, 2H), 3.82 (s, 3H), 1.39 (t, J=7.0 Hz, 3H).

Provenance & Evidence