Pyridine → HCID 44176494, compound

Participants

Reaction Steps

Into an 8 mL vial was weighed 26.8 mg (52 μmol) of 1-(3′-(methylsulfonyl)biphenyl-4-yl)-4-((R)-pyrrolidin-2-yl)-2-(2-(trifluoromethyl)phenyl)-1H-imidazole. The vial was charged with 0.5 mL of THF, followed by 15 μL (185 μmol) of pyridine, and 7 μL (98 μmol) of acetyl chloride. After stirring for 30 minutes at ambient temperature, LC/MS analysis of the reaction showed complete conversion to product. The reaction was quenched by addition of a small amount of water. The reaction solution was directly injected into the reverse phase preparative HPLC and eluted with acetonitrile/water. (Phenomenex Axia Gemini C18 30×100 mm 5 μm, A=H2O with 0.1% trifluoroacetic acid, B=acetonitrile with 0.1% trifluoroacetic acid, 17 minute gradient from 10% B to 100% B at 35 mL/minute). Product fractions were combined, made basic by the addition of sat. NaHCO3, and concentrated in vacuo to remove the acetonitrile. The resulting basic aqueous was extracted with CH2Cl2 (3×), and the organics were dried over Na2SO4, filtered and concentrated in vacuo. The resulting 1-((2R)-2-(1-(3′-(methylsulfonyl)biphenyl-4-yl)-2-(2-(trifluoromethyl)phenyl)-1H-imidazol-4-yl)pyrrolidin-1-yl)ethanone was isolated as a white powder, yield 20.2 mg (70%); 1H NMR (400 MHz, CDCl3): δ 8.10-8.07 (m, 1H), 7.95-7.90 (m, 1H), 7.83-7.79 (m, 1H), 7.77-7.72 (m, 1H), 7.67-7.61 (m, 1H), 7.56-7.42 (m, 4H), 7.38-7.34 (m, 0.6H), 7.30-7.26 (m, 0.4H), 7.20-7.16 (m, 2.4H), 7.05-7.04 (m, 0.6H), 5.34-5.31 (m, 0.4H), 5.08-5.05 (m, 0.6H), 3.78-3.67 (m, 1H), 3.63-3.49 (m, 1H), 3.09 (s, 1.8H), 3.08 (s, 1.2H), 2.52-2.46 (m, 0.4H), 2.36-2.26 (m, 1.6H), 2.14 (s, 1.8H), 2.12 (s, 1.2H), 2.08-1.95 (m, 2H); MS (ES): 554.3 [M+H]+.

Provenance & Evidence