Pyridine → 1-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-2-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]propan-1-one

Participants

Reaction Steps

2-[2-Methyl-4-(trifluoromethyl)imidazol-1-yl]propanoic acid (151 mg, 0.679 mmol) was dissolved in dichloromethane (2 mL) at room temperature. Oxalyl chloride (120 μL, 1.38 mmol) and a catalytic amount of dimethylformamide (1 μL) was added and the reaction was stirred at room temperature for 2 h. Solvent was removed under reduced pressure and the acid chloride was dried under vacuum. The crude acid chloride was dissolved in dichloromethane (2.1 mL). To a portion of this solution (0.7 mL, 0.22 mmol) was added 1-(4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[4,3-b]pyridine (41.5 mg, 0.191 mmol) and pyridine (55 μL, 0.68 mmol) at room temperature and the reaction mixture was stirred for 2 h. Water was added and the layers were separated. The aqueous layer was extracted twice more with dichloromethane. The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography (SiO2, 40-100% ethyl acetate in hexanes with 0.1% aqueous ammonium hydroxide) to afford the desired product as a white solid (70.1 mg, 0.166 mmol, 87%). 1H NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 7.45 (ddd, J=9.2, 4.8, 2.0 Hz, 2H), 7.17 (dt, J=9.2, 2.0 Hz, 2H), 5.21 (q, J=6.8 Hz, 1H), 3.75 (ddd, J=12, 7.2, 3.2 Hz, 1H), 3.51 (ddd, J=12, 8.0, 3.2 Hz, 1H), 2.84 (t, J=6.6 Hz, 2H), 2.47 (s, 3H), 1.96-2.09 (m, 2H), 1.72 (d, J=6.4 Hz, 3H); MS: (ES) m/z calculated for C20H19N5OF4 [M+H]+ 422, found 422.

Provenance & Evidence