反应详情

49 mg (1 eq, 0.1 mmol) of 4-[(1E)-3-oxo-3-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-amino)prop-1-en-1-yl]-2-(trifluoromethyl)benzoic acid from Example 2, Stage 2 were dissolved in 1 ml of dichloromethane. Then 17 mg (1.0 eq, 0.10 mmol) of 6-chlorohydroxybenzotriazole, 23 mg (1.2 eq, 0.12 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride and 26 mg (2 eq, 0.20 mmol) of N-ethyldiisopropylamine were added thereto, and the mixture was stirred at RT for 20 min. Subsequently, 11 mg (1.0 eq, 0.10 mmol) of 1-fluoropropan-2-amine hydrochloride were added and the reaction mixture was stirred at room temperature for 12 h. After this time, the reaction mixture was concentrated and the resulting crude product was purified by means of preparative HPLC (phenomenex Gemini C18 5 μm; 110A; AXIA 50×21.2 mm; gradient: 0-2 min 70% water, 30% MeOH, 2.5-6.0 min linear gradient to 5% water, 95% MeOH, 6.0-20.00 min 5% water, 95% MeOH; modifier: 20% HCOOH added at 2 ml/min). This gives 27 mg (37%) of N-(1-fluoropropan-2-yl)-4-[(1E)-3-oxo-3-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}amino)-prop-1-en-1-yl]-2-(trifluoromethyl)benzamide as a solid.

1. stirringthe reaction mixture was stirred at room temperature for 12 h
2. concentrationAfter this time, the reaction mixture was concentrated
3. customthe resulting crude product was purified by means of preparative HPLC (phenomenex Gemini C18 5 μm
4. custom0-2 min 70% water, 30% MeOH, 2.5-6.0 min
5. customto 5% water, 95% MeOH, 6.0-20.00 min 5% water, 95% MeOH
6. additionmodifier: 20% HCOOH added at 2 ml/min)