Reaction Steps
A microwave vial containing a mixture of 4-(2-(5-bromo-1H-indazol-1-yl)ethyl)morpholine (549 mg, 1.77 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (494 mg, 1.95 mmol), potassium acetate (347 mg, 3.54 mmol) and PdCl2(dppf)-CH2Cl2 adduct (72 mg, 0.088 mmol) was flushed with nitrogen. Dioxane (4.5 mL) was added, the vial was sealed and heated at 100° C. for 5 hrs. This was diluted with EtOAc, washed with water and brine, and dried over MgSO4. Removal of the solvent left crude 4-(2-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol-1-yl)ethyl)morpholine (1 gm) as a oil which was used as such. A microwave vial containing a mixture of 2-bromo-7-morpholino-5H-pyrido[3,2-b]indole-4-carboxamide (50 mg, 0.120 mmol), crude 4-(2-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol-1-yl)ethyl)morpholine (83 mg, 0.17 mmol), and PdCl2(dppf)-CH2Cl2 adduct (9.8 mg, 0.012 mmol), was flushed with nitrogen. DME (2 mL) and aq. Na2CO3 (0.30 mL, 0.60 mmol, 2.0 M) were added and the vial was sealed and heated at 100° for 6 hrs. Preparative HPLC (100×30 mm Luna C18 column, Solvent A=10% Methanol, 90% H2O, 0.1% TFA; Solvent B=90% Methanol, 10% H2O, 0.1% TFA, elution gradient of 0 to 60% B over 20 min at 42 mL/min) followed by SCX capture and release with 2 N NH3 in MeOH afforded 7-morpholino-2-(1-(2-morpholinoethyl)-1H-indazol-5-yl)-5H-pyrido[3,2-b]indole-4-carboxamide (35 mg, 0.067 mmol, 56% yield) as a solid. MS (ESI) m/z 526.24 (M+H). 1H NMR (500 MHz, DMSO-d6) δ ppm 11.21 (1H, s), 8.61 (1H, s), 8.55 (1H, br. s.), 8.37 (1H, dd, J=9.16, 1.53 Hz), 8.35 (1H, s), 8.19 (1H, s), 8.10 (1H, d J=8.85 Hz), 7.79-7.86 (2H, m), 7.23 (1H, d, J=1.83 Hz), 7.02 (1H, dd, J=8.70, 1.98 Hz), 4.58 (2H, t, J=6.56 Hz), 3.77-3.87 (4H, m), 3.49-3.56 (4H, m), 3.21-3.27 (4H, m), 2.82 (2H, t, J=6.56 Hz), 2.41-2.49 (4H, m).
