Cesium carbonate → HCID 59276173, compound

Participants

Reaction Conditions

Reaction Steps

4-((2-(1-Tosyl-1H-pyrrolo[2,3-b]pyridin-5-ylamino)-[1,2,4]triazolo[1,5-a]pyridin-5-yl)methyl)piperazin-2-one. A mixture of tris(dibenzylideneacetone)dipalladium(0) (0.019 g, 0.020 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.023 g, 0.041 mmol) in 1,4-dioxane (1.25 mL) was added to 5-bromo-1-tosyl-1H-pyrrolo[2,3-b]pyridine (0.086 g, 0.244 mmol), 4-((2-amino-[1,2,4]triazolo[1,5-c]pyridin-5-yl)methyl)piperazin-2-one (0.050 g, 0.203 mmol), and cesium carbonate (0.265 g, 0.812 mmol) in a 1 dram vial with a stirbar. Nitrogen was blown in to blow out air. The resulting mixture was sealed, stirred vigorously, and heated at 100° C. for 2 h 20 min. The resulting mixture was diluted with acetonitrile, filtered, and purified using reverse-phase semi-preparatory HPLC (10-70% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, over 34 min). Fractions containing the desired product were combined and loaded onto a Strata X—C ion exchange column from Phenomenex. The column was washed successively with water, acetonitrile, methanol, and then 5% ammonium hydroxide in methanol. The product came off with the 5% ammonium hydroxide in methanol eluent and was concentrated on a rotary evaporator and dried under high vacuum at 40° C. to give the desired product (0.062 g, 0.116 mmol, 57% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 9.91 (s, 1H), 8.59 (s, 1H), 8.48 (s, 1H), 7.97 (d, J=7.81 Hz, 2H), 7.77-7.88 (m, 2H), 7.56-7.64 (m, 1H), 7.49-7.56 (m, 1H), 7.42 (d, J=7.81 Hz, 2H), 7.10 (d, J=7.03 Hz, 1H), 6.82 (d, J=3.90 Hz, 1H), 4.08 (s, 2H), 3.13-3.27 (m, 4H), 2.77 (br s, 2H), 2.34 (s, 3H); MS (ESI) m/z 517.1 [M+1]+.

Provenance & Evidence