[CH2:1]([C:3]1([CH3:9])[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1)[CH3:2].CCN(C(C)C)C(C)C.[Br:19][C:20]1[C:21](Cl)=[C:22]([C:28](=[O:35])[C:29]([O:31][CH:32]([CH3:34])[CH3:33])=[O:30])[C:23]([CH3:27])=[N:24][C:25]=1[CH3:26]>CC#N.CCOCC>[Br:19][C:20]1[C:21]([N:6]2[CH2:7][CH2:8][C:3]([CH2:1][CH3:2])([CH3:9])[CH2:4][CH2:5]2)=[C:22]([C:28](=[O:35])[C:29]([O:31][CH:32]([CH3:33])[CH3:34])=[O:30])[C:23]([CH3:27])=[N:24][C:25]=1[CH3:26]To a solution of 4-ethyl-4-methylpiperidine (0.760 g, 5.98 mmol) and DIEA (2.1 mL, 11.9 mmol) in anhydrous CH3CN (15 mL) was added isopropyl 2-(5-bromo-4-chloro-2,6-dimethylpyridin-3-yl)-2-oxoacetate (2.0 g, 5.98 mmol) at rt. The resulting mixture was placed in a pre-heated oil bath (80° C.) and stirred for 24 h; cooled, diluted with ether, washed with water, brine, and dried (MgSO4). The crude product was charged (DCM) to a 80 g ISCO silica gel cartridge and gradient eluted (5-15% EtOAc/hexanes) using an Isolera chromatography station to give isopropyl 2-(5-bromo-4-(4-ethyl-4-methylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-oxoacetate 2.51 g (99%). 1H NMR (500 MHz, CDCl3) δ 5.07-5.02 (m, 1H), 3.32 (br. s, 2H), 3.18 (br.s, 2H), 2.61 (s, 3H), 2.29 (s, 3H), 1.29-1.28 (m 12H), 0.89 (s, 3H), 0.80 (t, J=7.3 Hz, 3H). UPLC (M+H)=427.3.
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