反应详情

To a solution of 2,5-dimethyl-4-[4-(trifluoromethyl)benzyl]thiophene-3-carboxylic acid from Example 11, Step 4 (4.36 g, 1 eq.) and (1S)-1-[4-(methoxycarbonyl)phenyl]ethanaminium chloride from Example 1, Step 9 (3.29 g, 1.10 eq.) in dimethylformamide (50 mL) is added HATU (5.65 g, 1.07 eq.) in one portion. After stirring for 2 minutes, diisopropylethylamine (6.0 mL, 2.5 eq.) was added in one portion and the reaction stirred until consumption of the starting acid. The reaction was poured onto half-saturated sodium bicarbonate (400 mL) and the white suspension stirred vigorously for 30 minutes. The solids were collected by filtration, washed with water while onto the Buchner, dried and purified by chromatography on silica gel (2:98 to 10:90 EtOAc/CHCl3) to afford the desired product as a white solid. MS (+APCI): m/z 476 (M+1)+.

1. stirringthe reaction stirred until consumption of the starting acid
2. stirringthe white suspension stirred vigorously for 30 minutes
3. filtrationThe solids were collected by filtration
4. washwashed with water while onto the Buchner
5. customdried
6. custompurified by chromatography on silica gel (2:98 to 10:90 EtOAc/CHCl3)