2,6-Lutidine → HCID 67189242, compound

Participants

Reaction Conditions

Reaction Steps

To a solution containing 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in PCT WO 2004/052869 A1, Example 1, 100 mg, 0.30 mmol) in methylene chloride (20 mL), was then added a 2.0 M solution of oxalylchloride in methylene chloride (181 μL, 0.36 mmol) at 0° C. and allowed to stir at 25° C. for 1 h, after which time 2,6-lutidine (70 μL, 0.61 mmol) was added to the solution at 0° C. After 1 h, crude 4-(3-amino-pyrazol-1-ylmethyl)-benzonitrile (0.42 mmol based on theory) was added and the reaction was allowed to proceed for 16 h. The reaction solution was washed with 1.0 M aqueous hydrochloric acid solution, dried over sodium sulfate, concentrated in vacuo and purified by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 0% methanol/methylene chloride to 10% methanol/methylene chloride) to afford 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(4-cyano-benzyl)-1H-pyrazol-3-yl]-3-cyclopentyl-propionamide (35 mg, 23%) as a white solid: ESI-LRMS m/e calcd for C26H27ClN4O3S [M+] 510.2, found 511.5 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.06-1.21 (m, 2H, CH2), 1.44-1.92 (m, 8H, 4×CH2), 2.09-2.35 (m, 1H, CH), 3.25 (s, 3H, SO2CH3), 3.56 (t, J=7.5 Hz, 1H, CH), 5.20 (s, 2H, NCH2), 6.74 (d, J=2.3 Hz, 1H, Ar), 7.19 (d, Jo=8.4 Hz, 2H, Ar), 7.35 (d, J=2.3 Hz, 1H, Ar), 7.44 (dd, Jo=8.2, Jm=1.7 Hz. 1H, Ar), 7.54-7.63 (m, 3H, Ar), 7.99 (s, 1H, NH), 8.06 (d, Jo=8.2 Hz, 1H, Ar).

Provenance & Evidence