反应详情

温度

0 °C

To a stirred solution of 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-3-methylbutanoic acid (14 mg, 0.045 mmol) and diisopropylethylamine (0.05 mL) in anhydrous DMF (0.3 mL) was added HATU (30 mg, 0.079 mmol) at 0° C. under argon. After stirring at 0° C. for 5 min, 2-aminothiazole (15 mg, 0.15 mmol) was added. The reaction mixture was stirred at rt for 5 min and 50° C. for 30 min. Purification using reverse phase HPLC (YMC S5 20×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA) gave 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-3-methyl-N-(thiazol-2-yl)butanamide (Example 114, 9 mg, 0.02 mmol, 44% yield) as a white solid. MS found: (M+H)+=395. 1H-NMR (400 MHz, CDCl3) δ ppm 8.04 (1H, s) 7.67 (1H, s) 7.58 (2H, dd, J=8.90, 4.83 Hz) 7.53 (1H, d, J=9.16 Hz) 7.40-7.46 (1H, m) 7.25 (1H, s) 7.14 (2H, t, J=8.65 Hz) 6.87 (1H, s) 2.81 (2H, s) 1.51 (6H, s).

1. stirringThe reaction mixture was stirred at rt for 5 min and 50° C. for 30 min
2. customPurification
3. customphase HPLC (YMC S5 20×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA)