Lithium Chloride → 6-(1-Methyl-1H-imidazol-5-yl)-3-(4-piperidin-1-ylmethylphenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-bromo-3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (100 mg, 0.16 mmol), 1-methyl-5-(tributylstannyl)-1H-imidazole (120 mg, 0.32 mmol), tetrakis(triphenylphosphine)palladium(0) (18 mg, 0.016 mmol) and lithium chloride (68 mg, 1.6 mmol) in 1,4-dioxane (3 mL) was degassed and flushed with nitrogen and the reaction heated at 100° C. for 16 h. The cooled reaction mixture was diluted with DCM (20 mL) and methanol (2 mL) and washed with water (15 mL). The organic phase was separated, dried over sodium sulfate, filtered and evaporated in vacuo to afford a residue that was purified by flash chromotagraphy (silica, 10 g column, Biotage, 0-10% methanol in (DCM containing 1% 7M ammonia in methanol)) to afford a residue that was purified by preparative HPLC [20-60% MeCN in water (0.1% ammonium hydroxide) over 30 min, 35 mL/min] to afford the title compound as a pale orange solid (13 mg, 20%). 1H NMR (DMSO-D6, 400 MHz): 12.26 (s, 1H), 9.04 (d, J=2.2 Hz, 1H), 8.95 (d, J=0.9 Hz, 1H), 8.92 (d, J=2.2 Hz, 1H), 8.58 (d, J=0.9 Hz, 1H), 7.77 (d, J=8.2 Hz, 2H), 7.72 (s, 1H), 7.44 (d, J=8.1 Hz, 2H), 7.39 (d, J=1.0 Hz, 1H), 3.96 (s, 3H), 3.49 (s, 2H), 2.36 (s, 4H), 1.57-1.47 (m, 4H), 1.40 (m, 2H). LCMS (Method D): KT=6.54 min, M+H+=423.

Provenance & Evidence