2,6-Lutidine → 2(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(1-methanesulfonylmethyl-1H-pyrazol-3-yl)-propionamide

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

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 (166 μL, 0.33 mmol) at 0° C. and allowed to stir at 25° C. for 1 h, after which time 2,6-lutidine (46 μL, 0.39 mmol) was added to the solution at 0° C. After 1 h, 1-methanesulfonylmethyl-1H-pyrazol-3-ylamine (0.30 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)-3-cyclopentyl-N-(1-methanesulfonylmethyl-1H-pyrazol-3-yl)-propionamide (133 mg, 90%) as a white solid: ESI-LRMS m/e calcd for C20H26ClN3O5S2 [M+] 487.1, found 488.4 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.03-1.22 (m, 2H, CH2), 1.43-1.94 (m, 8H, 4×CH2), 2.09-2.29 (m, 1H, CH), 2.86 (s, 3H, SO2CH3), 3.27 (s, 3H, SO2CH3), 3.58 (t, J=7.5 Hz, 1H, CH), 5.25 (s, 2H, NCH2), 6.87 (d, J=2.5 Hz, 1H, Ar), 7.48 (dd, Jo=8.1, Jm=1.6 Hz. 1H, Ar), 7.54 (d, J=2.5 Hz, 1H, Ar), 7.61 (d, Jm=1.6 Hz, 1H, Ar), 8.01 (d, Jo=8.1 Hz, 1H, Ar), 8.10 (brs, 1H, NH).

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