CC([PH+](C(C)(C)C)CCCS([O-])(=O)=O)(C)C.[Cl:17][C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[N:22][CH:23]=1.Br[C:28]1[CH:45]=[C:44]2[C:31]([CH2:32][C:33]3([C:37]42[N:41]=[C:40]([NH2:42])[C:39]([CH3:43])=[N:38]4)[CH2:36][CH2:35][CH2:34]3)=[CH:30][CH:29]=1.CC1CCCO1.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.[Na+].[Na+].Cl[Pd+2](Cl)(Cl)Cl>[Cl:17][C:18]1[CH:19]=[C:20]([C:28]2[CH:45]=[C:44]3[C:31]([CH2:32][C:33]4([C:37]53[N:41]=[C:40]([NH2:42])[C:39]([CH3:43])=[N:38]5)[CH2:36][CH2:35][CH2:34]4)=[CH:30][CH:29]=2)[CH:21]=[N:22][CH:23]=1Sodium tetrachloropalladate (II) (2.77 mg, 9.43 μmol), 3-(di-tert-butylphosphonium)propane sulfonate (5.06 mg, 0.02 mmol), 5-chloropyridin-3-ylboronic acid (40.6 mg, 0.25 mmol) and 6′-bromo-5″-methyl-3′H-dispiro[cyclobutane-1,2′-indene-1′,2″-imidazol]-4″-amine (Example 54, 60 mg, 0.19 mmol), was added to a vial. 2-Methyl-tetrahydrofuran (1 mL) and 2 M aq. K2CO3 (0.283 mL, 0.57 mmol) was added and the mixture was degassed by bubbling N2 (g). The vial was sealed and heated in a microwave reactor at 90° C. for 30 min. EtOAc (5 mL) and water (5 mL) were added and the phases were separated. The aq phase was extracted with EtOAc and the combined organic layers were dried over MgSO4, filtered and concentrated in vacuo. Purification by flash chromatography using a gradient of 0-10% MeOH, containing 1.2% 7M NH3 in MeOH, in DCM, afforded 51 mg of the title compound (77% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.62 (m, 4 H) 1.83 (d, 1 H) 2.16 (s, 1 H) 2.21 (s, 3 H) 3.23 (d, 2 H) 6.60 (s, 2 H) 6.94 (d, 1 H) 7.43 (d, 1 H) 7.58 (dd, 1 H) 8.10 (t, 1 H) 8.57 (d, 1 H) 8.71 (d, 1 H); MS (ES+) m/z 351 [M+H]+.
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