反应详情

温度

25 °C

N-[1-(3-Amino-benzyl)-1H-pyrazol-3-yl]-2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide prepared in example 58 (110 mg, 0.22 mmol) was dissolved in methylene chloride (2 mL) and N-methyl-morpholine (26 μL, 0.24 mmol) was added. Propionyl chloride (19 μL, 0.22 mmol) was added and the reaction stirred at 25° C. for 30 min. The reaction was concentrated in vacuo to give a beige foam. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 0% ethyl acetate/methylene chloride to 20% ethyl acetate/methylene chloride) afforded 2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(3-propionylamino-benzyl)-1H-pyrazol-3-yl]-propionamide (75 mg, 61%) as a white powder: ESI-LRMS m/e calcd for C28H33ClN4O4S [M+] 556.19, found 557.27 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.07-1.19 (m, 2H, CH2), 1.23 (t, J=7.5 Hz, 3H, CH3), 1.41-1.92 (m, 8H, 4×CH2), 2.15-2.27 (m, 1H, CH), 2.36 (m, 2H, NCOCH2), 3.25 (s, 3H, SO2CH3), 3.56 (t, J=7.75 Hz, 1 H, CH), 5.09 (s, 2H, NCH2), 6.68 (d, J=2.0 Hz, 1H, Ar), 6.86 (d, Jo=7.8 Hz, 1H, Ar), 7.18-7.23 (m, 1H, Ar), 7.24 (s, 1H, NH), 7.30 (d, J=2.0 Hz, 1H, Ar), 7.33-7.42 (m, 2H, Ar), 7.44 (d, Jo=8.2 Hz. 1H, Ar), 7.58 (s, 1H, Ar), 8.04 (d, Jo=8.2 Hz. 1H, Ar), 8.05 (brs, 1H, NH).

1. concentrationThe reaction was concentrated in vacuo
2. customto give a beige foam
3. customPurification by flash column chromatography (Merck silica gel 60, 40-63 μm; 0% ethyl acetate/methylene chloride to 20% ethyl acetate/methylene chloride)