Br[C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][CH2:8][N:7]([C:11]3[S:12][C:13]4[CH2:14]C(C)(C)N[C:17](=O)[C:18]=4[N:19]=3)[C:6]=2[CH:23]=1.CC1(C)C(C)(C)OB([C:32]2[CH:33]=[N:34][N:35]([CH2:37][CH2:38][N:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)[CH:36]=2)O1.C([O-])([O-])=O.[K+].[K+].[OH2:52]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:5][C:6]1([CH3:23])[NH:7][C:14](=[O:52])[C:13]2[S:12][C:11]([N:7]3[C:6]4[CH:23]=[C:2]([C:32]5[CH:33]=[N:34][N:35]([CH2:37][CH2:38][N:39]6[CH2:40][CH2:41][O:42][CH2:43][CH2:44]6)[CH:36]=5)[CH:3]=[CH:4][C:5]=4[O:10][CH2:9][CH2:8]3)=[N:19][C:18]=2[CH2:17]1A stirred solution of Example 39 (0.1 g, 0.326 mmol), 4-{2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazol-1-yl]ethyl}morpholine (0.051 g, 0.165 mmol), K2CO3 (0.054 g, 0.395 mmol), tetra-n-butylammonium bromide (0.122 g, 0.377 mmol), tetrakis(triphenylphosphine)palladium(0) (0.007 g, 0.006 mmol) and H2O (0.5 mL) in THF (1 mL) was heated at 125° C. in a sealed vessel for 2.5 days. After cooling to r.t. the reaction mixture was diluted with EtOAc and washed with water and brine. The organic fraction was dried (MgSO4), filtered and concentrated in vacuo. Purification by column chromatography (SiO2, 0-100% [9:1 EtOAc/MeOH]/heptane) followed by trituration with Et2O gave the title compound (0.026 g, 41%) as a white solid. δH (CDCl3) 8.00 (1H, d, J 2.1 Hz), 7.72 (1H, s), 7.68 (1H, s), 7.20 (1H, dd, J 8.5 and J 2.1 Hz), 6.97 (1H, d, J 8.5 Hz), 5.27 (1H, br. s), 4.39-4.26 (4H, m), 4.25-4.19 (2H, m), 3.78-3.69 (4H, m), 2.95-2.83 (4H, m), 2.61-2.49 (4H, m), 1.42 (6H, s). LCMS (ES+) 495.5 (M+H)+, RT 2.04 minutes (Method 1).
Wird geladen…