反应详情

温度

0 °C

A 250 mL round bottom flask was charged with a magnetic stir bar, (R or S)-1-(1-(1-(tert-butoxycarbonyl)piperidin-4-yl)ethyl)-2-methyl-1H-indole-3-carboxylic acid (1.950 g, 5.05 mmol), 3-(aminomethyl)-4-methoxy-6-methylpyridin-2(1H)-one hydrochloride (2.065 g, 10.09 mmol), DMF (25.2 ml, 5.05 mmol). Hunig's base (3.52 ml, 20.18 mmol). The reaction mixture was cooled to 0° C. and COMU (2.16 g, 5.05 mmol) was added. The reaction was allowed to stir overnight to room temperature. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic extract was washed with brine, dried with MgSO4, filtered and conc. in vacuo to afford the crude material which was purified via silica gel chromatography (120 g) using MeOH/ethyl acetate (1:5) as eluent to afford the title compound (1.86 g, 3.29 mmol, 65.3% yield). LCMS 537 (M+1)+ 1H NMR (400 MHz, DMSO-d6) δ=11.83-11.71 (m, 1 H), 7.80 (br. s., 1 H), 7.73 (d, J=7.6 Hz, 1 H), 7.62 (d, J=7.8 Hz, 1 H), 7.06 (td, J=7.1, 14.4 Hz, 2 H), 6.21 (s, 1 H), 4.32 (br. s., 2 H), 4.16 (br. s., 1 H), 4.02 (br. s., 1 H), 3.85 (s, 3 H), 3.75 (br. s., 1 H), 2.70 (br. s., 1 H), 2.58 (s, 3 H), 2.37 (br. s., 1 H), 2.21 (s, 3 H), 1.90 (d, J=12.9 Hz, 1 H), 1.53 (d, J=6.9 Hz, 3 H), 1.35 (s, 10H), 1.21 (br. s., 1 H), 0.89 (d, J=8.7 Hz, 1 H), 0.67 (d, J=11.8 Hz, 1 H).

1. additionA 250 mL round bottom flask was charged with a magnetic stir bar
2. extractionextracted with EtOAc
3. extractionThe combined organic extract
4. washwas washed with brine
5. dry with materialdried with MgSO4
6. filtrationfiltered and conc. in vacuo
7. customto afford the crude material which
8. customwas purified via silica gel chromatography (120 g)