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

Participants

Reaction Steps

1-Methyl-3-(1-methylethyl)-5-(4-morpholinyl)-1H-indole-7-carboxylic acid (62.5 mg, 0.21 mmol), 3-(aminomethyl)-4,6-dimethyl-2(1H)-pyridinone.HCl (58.5 mg, 0.31 mmol) and 1-hydroxy-7-azabenzotriazole (47.8 mg, 0.35 mmol) were stirred in 2 mL of DMSO for 10 min under nitrogen. N-methylmorpholine (0.095 mL, 0.87 mmol) was added along with EDC (67.4 mg, 0.35 mmol) and the mixture was stirred at rt overnight under nitrogen. Ice-water was added but no solid crashed out. The reaction mixture was concentrated until only DMSO was left and purified using a reversed-phase HPLC (30×100 Varian Polaris C18, 15-80% gradient of MeCN in water with 0.1% TFA over 12 minutes). Fractions containing the desired product were evaporated until a minimum of water remained and saturated solution of NaHCO3 was added. The light orange solids that crashed out were filtered off and dissolved in DMF. Water was added and the solids that crashed out were filtered, air-dried for 15 min and dried in vacuum-oven overnight to give N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-methyl-3-(1-methylethyl)-5-(4-morpholinyl)-1H-indole-7-carboxamide (24 mg, 26.1% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.49 (s, 1H) 8.33 (t, J=4.93 Hz, 1H) 7.04 (d, J=2.27 Hz, 1H) 6.96 (s, 1H) 6.80 (d, J=2.27 Hz, 1H) 5.87 (s, 1H) 4.33 (s, 1H) 4.31 (s, 1H) 3.72-3.78 (m, 4H) 3.60 (s, 3H) 3.06-3.12 (m, 1H) 3.00-3.06 (m, 4H) 2.22 (s, 3H) 2.11 (s, 3H) 1.26 (d, J=6.8 Hz, 6H). MS (ES) [M+H]+ 437.0.

Provenance & Evidence