2,6-Lutidine → HCID 67189982, compound

Participants

Reaction Conditions

Reaction Steps

Triphenylphosphine (173 mg, 0.66 mmol) was dissolved in methylene chloride (8 mL) and cooled to 0° C. To this solution was added N-bromosuccinimide (133 mg, 0.75 mmol) and was stirred at 0° C. until it was completely dissolved and became light purple in color. The 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in PCT WO 2004/052869 A1, Example 1, 146 mg, 0.44 mmol) was then added and it was stirred at 0° C. for 15 min and then warmed to 25° C. and stirred for 30 min. The mixture was chilled to 0° C. and 1-propyl-1H-pyrazol-3-ylamine (54 mg, 0.43 mmol) was added followed by 2,6-lutidine (154 μL, 1.32 mmol). The mixture was continued to stir at 0° C. for 30 min and then at 25° C. for 3 h. The reaction was diluted with ethyl acetate (50 mL), washed with water (3×20 mL) and saturated aqueous brine solution (2×20 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 10% ethyl acetate/hexanes to 70% ethyl acetate/hexanes) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(1-propyl-1H-pyrazol-3-yl)-propionamide (104 mg, 55%) as a white foam: ESI-LRMS m/e calcd for C21H28ClN3O3S [M+] 437.2, found 438.3 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 0.85 (t, J=7.4 Hz, 1H, CH3), 1.04-1.16 (m, 2H, CH2), 1.38-1.93 (m, 10H, 5×CH2), 2.10-2.41 (m, 1H, CH), 3.24 (s, 3H, SO2CH3), 3.59 (t, J=7.5 Hz, 1H, CH), 3.89 (t, J=7.0 Hz, 2H, NCH2), 6.61 (d, J=2.2, 1H, Ar), 7.23 (d, J=2.2, 1H, Ar), 7.44 (dd, Jo=8.2, Jm=1.3 Hz. 1H, Ar), 7.57 (d, Jm=1.3 Hz, 1H, Ar), 8.02 (d, Jo=8.2 Hz, 1H, Ar), 8.61 (s, 1H, NH).

Provenance & Evidence