反应详情

To a stirred solution of 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-4-phenylbutanoic acid (10 mg, 0.025 mmol) and diisopropylethylamine (0.05 mL) in anhydrous DMF (0.2 mL) was added HATU (25 mg, 0.066 mmol) at rt under argon. After stirring at rt for 10 min, 2-aminothiazole (15 mg, 0.15 mmol) was added. The reaction mixture was stirred at rt for 2.5 hr, 40° C. for 1 hr, and 80° 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)-2,2-dimethyl-4-phenyl-N-(thiazol-2-yl)butanamide (Example 138, 7 mg, 0.01 mmol, 40% yield) as a white solid. MS found: (M+H)+=485. 1H-NMR (400 MHz, CDCl3) δ ppm 8.00 (1H, s) 7.53-7.58 (3H, m) 7.44 (1H, d, J=8.65 Hz) 7.35 (1H, d, J=3.56 Hz) 7.23 (1H, d, J=7.63 Hz) 7.11-7.15 (2H, m) 6.89-6.99 (7H, m) 3.63 (1H, dd, J=10.43, 4.32 Hz) 2.97-3.08 (2H, m) 1.37 (3H, s) 1.18 (3H, s).

1. stirringThe reaction mixture was stirred at rt for 2.5 hr, 40° C. for 1 hr
2. wait80° C. for 30 min
3. customPurification
4. 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)