反应详情

A 20 mL, oven dried vial was charged with 5-bromo-1-methyl-3-(1-methylethyl)-1H-indole-7-carboxylic acid (0.10 g, 0.338 mmol), 3-(aminomethyl)-4-methyl-2(1H)-pyridinone (0.088 g, 0.506 mmol), 1-hydroxy-7-azabenzotriazole (0.069 g, 0.506 mmol) and EDC (0.097 g, 0.506 mmol). To the mixture was added dimethyl sulfoxide (DMSO) (3 mL) via syringe, followed by N-methylmorpholine (0.148 mL, 1.351 mmol). The mixture was capped and stirred at RT overnight. The reaction was poured into 60 mL water and the resultant mixture stirred for 10 min, then placed in a freezer for 10 min. The solids were filtered, washed with water (10 mL), air dried for 5 min, and placed in a vacuum oven (40° C.). The solid was dissolved in DCM/MeOH and absorbed onto silica gel and concentrated in vacuo to dryness. Purification by column chromatography (12 g Isco GOLD silica column; Gradient B: 5-85%, A: dichloromethane, B: 10% 2 M ammonia/methanol in chloroform) gave 5-bromo-1-methyl-3-(1-methylethyl)-N-[(4-methyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indole-7-carboxamide (85 mg, 0.200 mmol, 59.3% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.25 (d, J=6.82 Hz, 6H) 2.26 (s, 3H) 3.03-3.17 (m, 1H) 3.64 (s, 3H) 4.34 (d, J=4.80 Hz, 2H) 6.05 (d, J=6.57 Hz, 1H) 7.09 (d, J=1.77 Hz, 1H) 7.14 (s, 1H) 7.22 (d, J=6.82 Hz, 1H) 7.75 (d, J=1.77 Hz, 1H) 8.57 (t, J=4.80 Hz, 1H) 11.48 (br. s., 1H). MS (ES) [M+H]+ 415.9.

1. customA 20 mL, oven dried vial
2. customThe mixture was capped
3. waitplaced in a freezer for 10 min
4. filtrationThe solids were filtered
5. washwashed with water (10 mL), air
6. customdried for 5 min
7. customplaced in a vacuum oven (40° C.)
8. dissolutionThe solid was dissolved in DCM/MeOH
9. customabsorbed onto silica gel
10. concentrationconcentrated in vacuo to dryness
11. customPurification by column chromatography (12 g Isco GOLD silica column