Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([NH:13][CH2:14][C:15]3[C:16](=[O:23])[NH:17][C:18]([CH3:22])=[CH:19][C:20]=3[CH3:21])=[O:12])[CH:10]=1)[N:7]([CH3:24])[CH:6]=[C:5]2[CH:25]([CH3:27])[CH3:26].C(N(CC)CC)C.N#N>C(O)C.O1CCCC1.C(Cl)Cl.C(Cl)(Cl)Cl>[NH3:7].[CH3:11][OH:12].[CH3:21][C:20]1[CH:19]=[C:18]([CH3:22])[NH:17][C:16](=[O:23])[C:15]=1[CH2:14][NH:13][C:11]([C:9]1[CH:10]=[CH:2][CH:3]=[C:4]2[C:8]=1[N:7]([CH3:24])[CH:6]=[C:5]2[CH:25]([CH3:27])[CH3:26])=[O:12]
To a dried 50 mL round bottom flask, equipped with a stir bar and H2/N2 inlet was added 10% Pd/C(degussa) (0.025 g, 0.012 mmol). The vessel was degassed with N2 and EtOH (˜0.5 mL) was added. To the slurry was added a solution of 5-bromo-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-methyl-3-(1-methylethyl)-1H-indole-7-carboxamide (0.10 g, 0.232 mmol) (solid) in ethanol (6 mL) and hot tetrahydrofuran (THF) (1.0 mL), followed by triethylamine (0.032 mL, 0.232 mmol). The reaction was placed back under N2 and stirred for 5 min, then evacuated/refilled with H2 (3×). The reaction was stirred under a H2 balloon for 4 h. The reaction was then evacuated/refilled with N2 and diluted with DCM (10 mL). A small amount of Celite was added and the reaction stirred for 10 min. The mixture was filtered through analytical grade Celite and washed with successively with 10% MeOH/DCM, EtOH, and DCM. The organics were concentrated and dried on hivac overnight. The residue was dissolved in MeOH/DCM, absorbed onto silica gel, and concentrated in vacuo to dryness. Purification by column chromatography (4 g Isco silica column; Gradient B: 5-85%, A: dichloromethane, B: 10% 2M ammonia/methanol in chloroform) gave N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-methyl-3-(1-methylethyl)-1H-indole-7-carboxamide (77 mg, 0.215 mmol, 92% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.27 (d, J=7.07 Hz, 6H) 2.11 (s, 3H) 2.22 (s, 3H) 3.06-3.19 (m, 1H) 3.65 (s, 3H) 4.33 (d, J=4.80 Hz, 2H) 5.86 (s, 1H) 6.91-6.99 (m, 1H) 6.99-7.08 (m, 2H) 7.59 (dd, J=7.83, 1.26 Hz, 1H) 8.31 (t, J=4.93 Hz, 1H) 11.47 (s, 1H). MS (ES) [M+H]+ 352.4.
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