2,6-Lutidine → HCID 24889329, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-oxo-cyclobutyl)-propionyl chloride in methylene chloride (0.036 M solution, 5 mL, 0.18 mmol) was slowly added to a cooled to 0° C. solution of 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in Example 80, 31 mg, 0.20 mmol) and 2,6-lutidine (31 μl, 0.27 mmol) in methylene chloride (6 ml). The reaction continued to stir at 0° C. for 15 min and then at 25° C. for 4 h. After concentration in vacuo it was purified on an AnaLogix Intelliflash system (40 g column, 100% ethyl acetate) to afford 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-3-(3-oxo-cyclobutyl)-propionamide (54 mg, 63%) as an off-white solid: [α]30589=−6.60° (c=5.9, CHCl3); 1H NMR (300 MHz, DMSO-d6) δ ppm 1.03, 1.04 (2×s, 6H, 2×CH3), 1.93-2.40 (m, 3H, CH and CH2), 2.66-2.85 (m, 2H, 2×CH or 2×CH2), 2.98-3.12 (m, 2H, 2×CH or 2×CH2), 3.34 (s, 3H, SO2CH3), 3.87 (s, 2H, NCH2), 3.85-3.91 (m, 1H, ArCHCO2), 6.46 (d, J=2.3 Hz, 1H, Ar), 7.52 (d, J=2.3 Hz, 1H, Ar), 7.61 (dd, Jm=1.6 Hz, Jo=8.3 Hz, 1H, Ar), 7.73 (d, Jm=1.6 Hz, 1H, Ar), 8.02 (d, Jo=8.3 Hz, 1H, Ar), 10.84 (s, 1H, NH).

Provenance & Evidence