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. Acetyl chloride (16 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 N-[1-(3-acetylamino-benzyl)-1H-pyrazol-3-yl]-2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (68 mg, 57%) as a white powder: ESI-LRMS m/e calcd for C27H31ClN4O4S [M+] 542.18, found 543.17 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.03-1.23 (m, 2H, CH2), 1.41-2.00 (m, 8H, 4×CH2), 2.15 (s, 3H, NCH3), 2.16-2.27 (m, 1H, CH), 3.25 (s, 3H, SO2CH3), 3.55 (t, J=7.5 Hz, 1H, CH), 5.09 (s, 2H, NCH2), 6.69 (d, J=2.3 Hz, 1H, Ar), 6.87 (d, Jo=7.5 Hz, 1H, Ar), 7.21-7.28 (m, 2H, NH and Ar), 7.28-7.33 (m, 2H, Ar), 7.35-7.41 (m, 1H, Ar), 7.44 (dd, Jo=8.1, Jm=1.3 Hz. 1H, Ar), 7.58 (d, Jm=1.3 Hz, 1H, Ar), 7.90-8.20 (m, 2H, Ar and 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)