Diisopropylethylamine → HCID 16041338, compound

Participants

Reaction Steps

Diisopropylethylamine (3.2 mL, 18 mmol) was added in one portion to a solution of (1R,2R)-5,5-difluoro-2-[4-[4-(methylsulfonyl)phenyl]-1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl]cyclohexanecarboxylic acid (1.69 g, 3.63 mmol), 1-aminocyclopropanecarbonitrile hydrochloride (1.16 g, 9.83 mmol) and HATU (1.72 g, 4.53 mmol) in DMF (10 mL) with stirring at rt for 2.5 h. The reaction vessel contents were then partitioned between ethyl acetate and water and the layers were separated. The aqueous phase was extracted with additional ethyl acetate and the combined organics were washed with 2 M HCl, 10% Na2CO3 and saturated NaCl aqueous solutions, followed by drying over Na2SO4. Concentration in vacuo and flash chromatography on silica gel eluting with 22.5/77.5 acetone/benzene provided the title compound as a colorless powder upon trituration with a mixture of hexanes and ether. 1H NMR (400 MHz, acetone d6) δ 8.03 (1H, s), 7.99 (2H, d, J= 8.5 Hz), 7.83 (1H, overlapped m), 7.81 (2H, d, J= 8.5 Hz), 5.05 (2H, q, J= 8.8 Hz), 3.36 (1H, m), 3.18 (3H, s), 3.12 (1H, m), 2.23 (1H, m), 2.15-1.95 (4H, m), 1.79 (1H, m), 1.37 (2H, m), 1.05 (1H, m), 0.81 (1H, m). MS: (+ESI) 531.0 [M+H]+.

Provenance & Evidence