反应详情

To a mixture of trans-3-thiophen-3-yl-acrylic acid (66 mg, 0.43 mmol) and oxalyl chloride (45 μL, 0.52 mmol) in 2 mL of CH2Cl2 was added a catalytic amount of DMF. After stirring at rt for 2 h, the mixture was concentrated in vacuo. The resulting crude acid chloride was dissolved in CH2Cl2 and treated with TEA (80 μL, 0.58 mmol) and 1-[6-(1-benzyl-piperidin-4-ylamino)-2,3-dihydro-indol-1-yl]-ethanone (0.100 g, 0.286 mmol). After stirring for 4 h, the mixture was washed with satd. aq. NaHCO3 followed by brine. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. Purification by silica gel chromatography (60% EtOAc/hexanes) afforded 118 mg (64%) of the title compound. 1H NMR (500 MHz, CDCl3): 8.02 (br s, 1H), 7.83 (d, J=15.7 Hz, 1H), 7.39-7.16 (m, 8H), 6.94-6.93 (m, 1H), 6.73-6.72 (m, 1H), 5.97 (d, J=15.7 Hz, 1H), 4.74-4.70 (m, 1H), 4.17-4.13 (m, 2H), 3.45 (br s, 2H), 3.28-3.23 (m, 2H), 2.88 (br s, 3H), 2.23 (s, 3H), 2.13 (m, 2H), 1.88-1.76 (m, 3H). MS: exact mass calculated for C29H18N3O2, 485.21; m/z found, 486.2 [M+H]+, 508.1 [M+Na]+.

1. concentrationthe mixture was concentrated in vacuo
2. dissolutionThe resulting crude acid chloride was dissolved in CH2Cl2
3. stirringAfter stirring for 4 h
4. washthe mixture was washed with satd
5. dry with materialThe organic layer was dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customPurification by silica gel chromatography (60% EtOAc/hexanes)