反应详情

温度

100 °C

A 250 ml round-bottom flask with magnetic stirrer was charged with 6-chloro-7-methylsulfanyl-9H-β-carbolin-8-ylamine (Intermediate 28, 2.336 g, 8.86 mmol) and 2-methylnicotinic acid (3.219 g, 23.4 mmol) in 80 ml anhydrous pyridine. To the resulting reaction mixture at RT was added solid 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (7.080 g, 36.9 mmol) and the reaction mixture was heated to 100° C. (oil bath) for 2 days. The resulting mixture was cooled to RT and concentrated (rotavap) to afford a brown residue. The residue was redissolved in MeOH (50 ml), slowly added to a stirring mixture of 5:1H2O/saturated aqueous sodium bicarbonate (600 mlL) and stirred at RT for 18 hr. The precipitated solid was collected via suction filtration, washed with Et2O (2×150 ml), and air-dried to afford 3.036 g of crude N-(6-chloro-7-methylsulfanyl-9H-β-carbolin-8-yl)-2-methyl-nicotinamide as a brown solid. The crude material was purified via HPLC (yields=˜40-60%). 1H-NMR (300 MHz, DMSO-d6): δ 11.72 (1H, s) 10.50 (1H, s) 8.97 (1H, s) 8.62 (1H, dd) 8.57 (1H, s) 8.41 (1H, d) 8.33-8.27 (1H, m) 8.21 (1H, d) 2.73 (3H, s) 2.41 (3H, s). LCMS (ammonium acetate standard method) retention time=1.89 min. MS (M+H+): 383.

1. customTo the resulting reaction mixture at RT
2. temperatureThe resulting mixture was cooled to RT
3. concentrationconcentrated (rotavap)
4. customto afford a brown residue
5. additionslowly added to a stirring mixture of 5
6. filtrationThe precipitated solid was collected via suction filtration
7. washwashed with Et2O (2×150 ml)
8. customair-dried