1,2-Dichloroethane → N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-methyl-3-(1-methylethyl)-5-(6-methyl-3-pyridinyl)-1H-indole-7-carboxamide

Participants

Reaction Steps

To a 20 mL vial was added 1-methyl-3-(1-methylethyl)-5-(6-methyl-3-pyridinyl)-1H-indole-7-carboxylic acid (0.10 g, 0.324 mmol), 3-(aminomethyl)-4,6-dimethyl-2(1H)-pyridinone (0.098 g, 0.519 mmol), 1-hydroxy-7-azabenzotriazole (0.088 g, 0.649 mmol) and EDC (0.124 g, 0.649 mmol). The reagents were diluted with DMSO (3 mL) and N-methylmorpholine (0.178 mL, 1.621 mmol). The mixture was stirred overnight, then slowly poured into ice-water (50 mL). The mixture was stirred for 10 min, then allowed to sit for 10 min. The mixture was then extracted with EtOAc (2×) and the combined organics washed with brine, dried over magnesium sulfate, and concentrated in vacuo. The residue was triturated with MTBE and the resulting solid dried in a vac oven at 45° C. for 4 h. Purified the solid by HPLC (Gilson; Sunfire 30×75 mm column; Gradient B: 10-65%; A: water+0.1% TFA; B: CH3CN+0.1% TFA). The residue was dissolved in 10% MeOH/DCM and treated with Silicycle carbonate resin (0.65 g) at 37° C. for 15 min. The mixture was allowed to cool to RT and was filtered through Celite. Concentrated in vacuo to give N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-methyl-3-(1-methylethyl)-5-(6-methyl-3-pyridinyl)-1H-indole-7-carboxamide (55 mg, 37.6% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.30 (d, J=6.82 Hz, 6H) 2.11 (s, 3H) 2.24 (s, 3H) 3.16-3.28 (m, 1H) 3.33 (s, 3H) 3.68 (s, 3H) 4.36 (d, J=5.05 Hz, 2H) 5.87 (s, 1H) 7.11 (s, 1H) 7.28-7.37 (m, 2H) 7.86 (d, J=1.77 Hz, 1H) 7.98 (dd, J=8.08, 2.53 Hz, 1H) 8.50 (t, J=4.93 Hz, 1H) 8.77 (d, J=2.27 Hz, 1H) 11.50 (s, 1H). MS (ES) [M+H]+ 443.2.

Provenance & Evidence