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. Ethanesulfonyl chloride (21 μL, 0.22 mmol) was added and the reaction stirred at 25° C. for 30 min. The reaction was warmed to 80° C. for 4 h. 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 60% ethyl acetate/methylene chloride) followed by preparative thin layer chromatography (Merck Silica gel 60 F254, 500 μm, 20×20 cm; 50% ethyl acetate/methylene chloride) afforded 2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(3-ethanesulfonylamino-benzyl)-1H-pyrazol-3-yl]-propionamide (14 mg, 11%) as a white powder: ESI-LRMS m/e calcd for C27H33ClN4O5S2 [M+] 592.2, found 593.7 [M+H+]; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.04-1.16 (m, 2H, CH2), 1.14 (t, J=7.3 Hz, 3H, CH3), 1.37-1.83 (m, 8H, 4×CH2), 2.01-2.16 (m, 1H, CH), 3.03 (q, J=7.3 Hz, 2H, SO2CH2), 3.32 (s, 3H, SO2CH3), 3.84-3.92 (m, 1H, CH), 5.15 (s, 2H, NCH2), 6.46 (d, J=2.2 Hz, 1H, Ar), 6.88 (d, Jo=7.7 Hz, 1H, Ar), 7.01 (t, Jm=1.6 Hz, 1H, Ar), 7.06-7.14 (m, 1H, Ar), 7.24 (t, Jo=7.7 Hz, 1H, Ar), 7.56 (dd, Jo=8.2, Jm=1.6 Hz, 1H, Ar), 7.66 (d, Jm=1.6 Hz, 1H, Ar), 7.69 (d, J=2.2 Hz, 1H, Ar), 7.98 (d, Jo=8.2 Hz, 1H, Ar), 9.75 (s, 1H, NH), 10.78 (s, 1H, NH).

1. temperatureThe reaction was warmed to 80° C. for 4 h
2. concentrationThe reaction was concentrated in vacuo
3. customto give a beige foam
4. customPurification by flash column chromatography (Merck silica gel 60, 40-63 μm; 0% ethyl acetate/methylene chloride to 60% ethyl acetate/methylene chloride)