1-(7-bromo-4-fluoro-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)ethane-1,2-dione → ethyl 3-(4-fluoro-3-(2-oxo-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)acetyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a sealed tube containing 1-(7-bromo-4-fluoro-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)ethane-1,2-dione (Compound B-1) (1.24 g, 2.48 mmol) in 1,4-dioxane (20 mL) was added ethyl 3-(tributylstannyl)-1H-pyrazole-5-carboxylate (1.12 g, 2.61 mmol) and Pd(PPh3)4(0.87 g, 0.75 mmol). The mixture was flushed with N2, and was sealed and heated to 100° C. After 14 h of heating, the mixture was cooled to rt, was diluted with MeOH, and was filtered through a pad of celite to remove any solids. The solution was concentrated under reduced pressure, and was re-dissolved in DMF. The DMF solution was loaded on the prep HPLC for purification. After purification, the title product was isolated as an off-white solid (0.901 g). LCMS: m/e 559.6 (M+H)+, ret time 2.283 min (method 2). 1H NMR (500 MHz, DMSO-D6) δ ppm 14.52 (s, 1 H) 12.35 (s, 1 H) 8.26-8.41 (m, 2 H) 7.36-7.76 (m, 6 H) 4.29-4.47 (m, J=6.71 Hz, 2 H) 3.09-3.80 (m, 8 H) 1.36 (s, 3 H).

Provenance & Evidence