Ammonia → 2-(1-methyl-1H-pyrazol-4-yl)-7-morpholino-5H-pyrido[3,2-b]indole-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

2-Bromo-7-morpholino-5H-pyrido[3,2-b]indole-4-carboxamide (50 mg, 0.12 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (50 mg, 0.24 mmol), and PdCl2(dppf)-CH2Cl2 adduct (9.79 mg, 0.012 mmol) in a microwave vial was flushed with nitrogen. DME (2 mL) and aq. Na2CO3 solution (0.30 mL, 0.60 mmol, 2.0 M) were added, the vial sealed, and heated at 100° C. for 3.5 hr. 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, 10 to 70% gradient over 20 min at 42 mL/min) followed by SCX capture and release with 2 N NH3 in MeOH gave 2-(1-methyl-1H-pyrazol-4-yl)-7-morpholino-5H-pyrido[3,2-b]indole-4-carboxamide (30 mg, 0.075 mmol, 63% yield) as a solid. MS (ESI) m/z 377.20 (M+H). 1H NMR (500 MHz, DMSO-d6) δ ppm 11.12 (1H, s), 8.36 (1H, br. s.), 8.25 (1H, s), 8.05 (1H, s), 8.01 (1H, s), 7.99 (1H, d, J=8.85 Hz), 7.79 (1H, s), 7.19 (1H, d, J=2.14 Hz), 6.98 (1H, dd, J=8.85, 2.14 Hz), 3.93 (3H, s), 3.77-3.84 (4H, m), 3.20-3.25 (4H, m).

Provenance & Evidence