2,6-Lutidine → (R)-2-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-3-((R)-3-oxo-cyclopentyl)-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 as in Example 80, 35 mg, 0.22 mmol), 2,6-lutidine (35 μL, 0.30 mmol) and methylene chloride (5 mL) which was then cooled to 0° C. in an ice bath. To this solution was then added dropwise a solution of (R)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-((R)-3-oxo-cyclopentyl)-propionyl chloride in methylene chloride (˜0.10 M solution, 2 mL, 0.20 mmol). The reaction was then allowed to warm up to 25° C. and stirred for 16 h. After this time the reaction mixture was diluted with methylene chloride (5 mL) transferred to a separatory funnel and washed with a saturated aqueous sodium bicarbonate solution (10 mL) and then a 1 N aqueous hydrochloric acid solution (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 100% ethyl acetate/hexanes) afforded (R)-2-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-3-((R)-3-oxo-cyclopentyl)-propionamide (88 mg, 91%) as a white foam: [α]30589=−79.0° (c=0.10, methylene chloride); ES-HRMS m/e calcd for C22H28N3O5SCl (M+H)+ 482.1511, observed 482.1511; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.03 (s, 3H, CH3), 1.04 (s, 3H, CH3), 1.50 (m, 1H, CH), 1.79-2.29 (m, 8H, 4×CH2), 3.34 (s, 3H, SO2CH3), 3.87 (s, 2H, NCH22), 3.96 (m, 1H, ArCHCO), 4.65 (s, 1H, OH), 6.45 (d, J=1.7 Hz, 1H, Ar), 7.51 (d, J=1.7 Hz, 1H, Ar), 7.62 (d, Jo=8.0 Hz, 1H, Ar), 7.73 (s, 1H, Ar), 8.02 (d, Jo=8.0 Hz, 1H, Ar), 10.85 (s, 1 H, NH).

Provenance & Evidence