[CH3:1][N:2]([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([O:14][C:15]([F:18])([F:17])[F:16])[C:9]=1[O:19][CH2:20][CH2:21][CH3:22])[C:3](=[O:6])[CH:4]=[CH2:5].C(N(C(C)C)CC)(C)C.Br[C:33]1[CH:46]=[N:45][C:36]2[NH:37][C:38](=[O:44])[C:39]([CH3:43])([CH3:42])[NH:40][CH2:41][C:35]=2[CH:34]=1.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)CC.CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:42][C:39]1([CH3:43])[C:38](=[O:44])[NH:37][C:36]2[N:45]=[CH:46][C:33](/[CH:5]=[CH:4]/[C:3]([N:2]([CH3:1])[CH2:7][C:8]3[CH:13]=[CH:12][CH:11]=[C:10]([O:14][C:15]([F:18])([F:16])[F:17])[C:9]=3[O:19][CH2:20][CH2:21][CH3:22])=[O:6])=[CH:34][C:35]=2[CH2:41][NH:40]1A solution of N-methyl-N-(2-propoxy-3-trifluoromethoxybenzyl)acrylamide (0.468 g, 1.47 mmol) in propionitrile (5 mL) and DMF (1 mL) was deoxygenated with Ar for 20 min. The solution was treated sequentially with diisopropylethylamine (0.40 mL, 2.3 mmol) and 7-bromo-3,3-dimethyl-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one (0.300 g, 1.11 mmol). The solution was deoxygenated with Ar for 20 min. Pd(OAc)2 (0.024 g, 0.111 mmol) and P(o-tol)3 (0.067 g, 0.222 mmol) were added and the solution was deoxygenated with Ar for 20 minutes. The mixture was heated to reflux for 18 h, then allowed to cool. The mixture was diluted with EtOAc (30 mL) and then washed with H2O (3×50 mL) and brine (2×100 mL), dried (Na2SO4) and concentrated to a yellow-orange solid. Purification by column chromatography (silica gel, CH2Cl2/MeOH, 100 to 98:2) gave the title compound (0.25 g, 31%) as an off-white solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 9.80-9.78 (m, 1H), 8.41-8.36 (m, 1H), 8.01-7.92 (m, 1H), 7.56-7.49 (m, 1H), 7.36-7.08 (m, 4H), 4.87-4.69 (m, 2H), 3.96-3.83 (m, 4H), 3.16-2.88 (m, 4H), 1.78-1.71 (m, 2H), 1.31-1.29 (m, 6H), 1.03-0.98 (m, 3H); MS (ESI) m/e 507 (M+H)+.
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