Phosgene → 2-isocyanato-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-benzamide

Participants

Reaction Steps

Into a 50 mL round bottomed flask were added 2-amino-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-benzamide (500 mg, 0.926 mmol), methylene chloride (10 mL) and sat'd NaHCO3(10 mL). The solution was cooled in an ice-water bath for 5 min then phosgene (2.5 mL, 20% w/w solution in toluene, Fluka) was added to the lower (organic) layer. The solution was stirred rapidly and the ice-bath was removed. The reaction mixture was stirred rapidly for 1 h, then the layers were separated and the aqueous phase was extracted 2× with methylene chloride. The combined organic fraction was treated with NaSO4, filtered and concentrated. The residue was triturated with anhydrous ether to give a light yellow/tan powder, which was used directly in the next step. Note: treatment of a small aliquot of the title compound with excess dimethylamine (2M, THF) followed by HPLC analysis provided evidence of isocyanate formation via transformation to the corresponding N,N-dimethyl urea; m/z=612.2 (M+H+).

Provenance & Evidence