反应详情

温度

70 °C

A mixture of (3S,4S)-benzyl 3-((3-carbamoyl-6-(6-((1,3-dioxoisoindolin-2-yl)methyl)pyridin-3-yl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-4-ethylpyrrolidine-1-carboxylate (57 mg, 0.089 mmol) and hydrazine, hydrate (8.29 μl, 0.266 mmol) in EtOH (2 mL) was heated to 70° C. for 10 minutes. THF (0.5 ml) was added to obtain homogeneity and heating was continued for 1.5 hr. Additional hydrazine, hydrate (8.29 μl, 0.266 mmol) (times 4; total of 12 equivalents) was added and heating was continued for 1.5 hr. A precipitation was observed. After cooling to rt, the reaction mixture was filtered and the filtrate was concentrated to a residue that was triturated with EtOAc. Filtration and drying afforded (3S,4S)-benzyl 3-((6-(6-(aminomethyl)pyridin-3-yl)-3-carbamoylpyrrolo[1,2-b]pyridazin-4-yl)amino)-4-ethylpyrrolidine-1-carboxylate (30 mg, 0.058 mmol, 66.0% yield) as a tan solid. The material is contaminated with the hydrazide by-product and will be used as is in the next step. MS (ES+) m/z: 514.4 (M+H); LC retention time: 2.303 min (analytical HPLC Method O).

1. customto obtain homogeneity
2. temperatureheating
3. temperatureheating
4. waitwas continued for 1.5 hr
5. customA precipitation
6. temperatureAfter cooling to rt
7. filtrationthe reaction mixture was filtered
8. concentrationthe filtrate was concentrated to a residue that
9. customwas triturated with EtOAc
10. filtrationFiltration
11. customdrying