Diisopropylethylamine → 3-(Pyridin-2-yl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

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Reaction Conditions

Reaction Steps

A solution of 3-bromo-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (150 mg, 0.549 mmol) and lithium chloride (69.9 mg, 1.65 mmol) in DMF (0.94 mL) was treated with DIPEA (239 μL, 1.37 mmol) and 2-(tributylstannyl)pyridine (607 μL, 1.65 mmol), and then degassed by the bubbling of nitrogen for 5 minutes. Tetrakis(triphenylphosphine)palladium(0) (31.7 mg, 27.5 μmol, 5.0 mol %) was added and the mixture heated at 165° C. for 15 h. The mixture was allowed to cool and treated with saturated aqueous potassium fluoride at ambient temperature. The resulting solids were removed by filtration and washed with 20% methanol in DCM and water. The filtrate was filtered through a pad of celite, washing with 20% methanol in DCM. The layers were separated, the aqueous phase extracted into 20% methanol in DCM, and the combined organic phases concentrated in vacuo to afford a solid residue. This solid was purified by preparative HPLC (0-30% MeCN/water modified with 0.1% formic acid) to afford an off-white solid powder (8.9 mg, 6.0%). 1H NMR (DMSO-D6, 400 MHz): 13.01 (s, 1H), 9.49 (d, J=2.2 Hz, 1H), 9.43 (d, J=2.2 Hz, 1H), 9.04 (dd, J=11.6, 0.8 Hz, 2H), 8.75 (d, J=4.0 Hz, 1H), 8.15 (d, J=8.0 Hz, 1H), 7.98 (td, J=7.8, 1.8 Hz, 1H), 7.43 (dd, J=6.7, 4.9 Hz, 1H). LCMS (Method D): RT=7.26 min, M+H+=272.

Provenance & Evidence