反应详情

温度

0 °C

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 (203 mg, 0.347 mmol) in acetonitrile (8 mL) at 0° C. was added TMS-I (0.189 mL, 1.386 mmol) and after stirring 15 minutes at 0° C., the cooling bath was removed. After stirring 4 hr at rt, the reaction mixture was re-cooled to 0° C. and 2 ml of MeOH were added. The mixture was allowed to warm to rt with stirring over 2 hr. At this time, the volatiles were removed in vacuo and the residue was triturated with ethyl ether. Filtration afforded a dark brown solid. Attempts to triturate with EtOAc were unsuccessful, so the mother liquor from the EtOAc trituration was recombined with the filter cake. The material was taken up in MeOH and was filtered. The filtrate was concentrated and was triturated with DCM. Filtration and drying afforded 4-(((3S,4S)-4-ethylpyrrolidin-3-yl)amino)-6-(6-((2-methoxyacetamido)methyl)pyridin-3-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide, 2hydroiodide (277 mg, 0.392 mmol, 113% yield) as a dark brown solid. The material will be used as is in the next step. MS (ES+) m/z: 452.4 (M+H); LC retention time: 1.453 min (analytical HPLC Method O).

1. customthe cooling bath was removed
2. stirringAfter stirring 4 hr at rt
3. temperaturethe reaction mixture was re-cooled to 0° C.
4. addition2 ml of MeOH were added
5. temperatureto warm to rt
6. stirringwith stirring over 2 hr
7. customAt this time, the volatiles were removed in vacuo
8. customthe residue was triturated with ethyl ether
9. filtrationFiltration
10. customafforded a dark brown solid
11. customto triturate with EtOAc
12. filtrationwas filtered
13. concentrationThe filtrate was concentrated
14. customwas triturated with DCM
15. filtrationFiltration
16. customdrying