Trimethylsilyl iodide → 4-(((3S,4S)-4-ethylpyrrolidin-3-yl)amino)-6-(6-((2-methoxyacetamido)methyl)pyridin-3-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide, dihydroiodide

Participants

Reaction Conditions

Reaction Steps

To a suspension of (3S,4S)-benzyl 3-((3-carbamoyl-6-(6-((2-methoxyacetamido)methyl)pyridin-3-yl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-4-ethylpyrrolidine-1-carboxylate (22 mg, 0.038 mmol) in Acetonitrile (1 mL) at 0° C. was added TMS-I (0.013 mL, 0.094 mmol) and after stirring 15 minutes at 0° C., the cooling bath was removed. At 3.5 hr, SM remained by HPLC. The reaction mixture was recooled to 0° C. and additional TMS-I (0.013 mL, 0.094 mmol) was added. After stirring 15 minutes at 0° C., the cooling bath was removed and the reaction mixture was stirred 2 hr at rt. The reaction mixture was recooled to 0° C. and 0.5 ml of MeOH was added. Stirring at 0° C. was continued for 30 minutes. At this time, the volatiles were removed in vacuo to afford crude 4-(((3S,4S)-4-ethylpyrrolidin-3-yl)amino)-6-(6-((2-methoxyacetamido)methyl)pyridin-3-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide, dihydroiodide (26 mg, 0.037 mmol, 98% yield) as a brown solid. The material was used as is in the next step.

Provenance & Evidence