Sodium bis(trimethylsilyl)amide → 6-Chloro-5-fluoro-9H-pyrrolo[2,3-b:5,4-c']dipyridine

Participants

Reaction Conditions

Reaction Steps

A solution of 6′-chloro-2,5′-difluoro-[3,4′]bipyridinyl-3′-ylamine (70 g, 290 mmol) in THF (300 mL) was added dropwise to a solution of sodium bis(trimethylsilyl)amide (720 mL, 1M in THF, 720 mmol) at such a rate that the reaction temperature was maintained at 40° C. When the addition was complete the mixture was stirred for ca. 1 hour at ambient temperature. The bulk of the solvent was evaporated in-vacuo and the residue poured into ice-cold 1N hydrochloric acid. The resulting slurry was filtered and the solid washed with water. The filter cake was collected and triturated with acetone followed by diethyl ether to afford the title compound as a beige solid (40.9 g, 64%). The trituration liquors were evaporated and the residue triturated with methanol followed by diethyl ether to afford a second crop of title compound as a brown solid (6.1 g, 10%). Total yield=47 g, 74%. 1H NMR (400 MHz, DMSO-d6): 13.24 (s, 1H), 8.91 (d, J=2.5 Hz, 1H), 8.77 (dd, J=4.8, 1.7 Hz, 1H), 8.65 (dd, J=7.9, 1.7 Hz, 1H), 7.50 (dd, J=7.9, 4.8 Hz, 1H).

Provenance & Evidence