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

Participants

Reaction Conditions

Reaction Steps

In a round bottom flask was placed 3-(3-amino-pyrazol-1-yl)-propan-1-ol (prepared in Example 23, 38 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 (prepared in Example 83, 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, 50% ethyl acetate/hexanes to 80% ethyl acetate/hexanes) afforded 3-cyclopentyl-N-[1-(3-hydroxy-propyl)-1H-pyrazol-3-yl]-2(R)-(3-trifluoromethyl-phenyl)-propionamide (56 mg, 57%) as a colorless oil: [α]30589=−20.0° (c=0.11, methylene chloride); ES-HRMS m/e calcd for C21H26N3O2F3 (M+H)+ 410.2050, observed 410.2050; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.01-1.19 (m, 2H, CH2), 1.34-1.80 (m, 8H, 4×CH2), 1.79-1.91 (m, 2H, CH2), 2.03-2.21 (m, 1H, CH), 3.29-3.38 (m, 2H, OCH2), 3.84-3.93 (m, 1H, ArCH), 4.01 (t, J=6.9 Hz, 2H, NCH2), 4.55 (t, J=5.0 Hz, 1H, OH), 6.41 (d, J=2.3 Hz, 1H, Ar), 7.54 (d, J=2.3 Hz, 1H, Ar), 7.55-7.74 (m, 4H, Ar), 10.74 (s, 1H, NH).

Provenance & Evidence