2,6-Lutidine → 3-cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2(R)-(3-trifluoromethyl-phenyl)-propionamide

Participants

Reaction Conditions

Reaction Steps

In a round bottom flask was placed 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in Example 80 42 mg, 0.27 mmol), 2,6-lutidine (42 μL, 0.37 mmol) and methylene chloride (5 mL). This solution was then cooled to 0° C. and to it was added dropwise a solution of 3-cyclopentyl-2(R)-(3-trifluoromethyl-phenyl)-propionyl chloride in methylene chloride (0.12 M solution, 2 mL, 0.24 mmol). The reaction was then allowed to warm up to 25° C. and stirred for 16 h. After this time the reaction was diluted with methylene chloride (5 mL). The reaction was then washed with a saturated aqueous sodium bicarbonate solution (10 mL) and a 1 N aqueous hydrochloric acid solution (1×10 mL) and then dried over magnesium sulfate, filtered and concentrated in vacuo. Purification on an AnaLogix Intelliflash system (4 g column, 20% ethyl acetate/hexanes to 60% ethyl acetate/hexanes) afforded 3-cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2(R)-(3-trifluoromethyl-phenyl)-propionamide (83 mg, 81%) as a white foam: [α]31589=−25.0° (c=0.14, methylene chloride); ES-HRMS m/e calcd for C22H28N3O2F3 (M+H)+ 424.2207, observed 424.2207; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.03 (s, 3H, CH3), 1.04 (s, 3H, CH3), 1.05-1.19 (m, 2H, CH2), 1.32-1.80 (m, 8 H, 4×CH2), 2.01-2.21 (m, 1H, CH), 3.86 (s, 2H, NCH2), 3.82-3.94 (m, 1H, ArCH), 4.64 (s, 1H, OH), 6.46 (d, J=2.3 Hz, 1H, Ar), 7.50 (d, J=2.3 Hz, 1H, Ar), 7.52-7.74 (m, 4H, Ar), 10.75 (s, 1H, NH).

Provenance & Evidence