反应详情

A solution of tert-butyl (3S)-1-(2,2,2-trifluoro-1-(6-hydrazinylpyridin-3-yl)ethyl)pyrrolidin-3-ylcarbamate (Example 1, Step D; 0.46 g, 1.03 mmol) and methyl 2-formylquinoline-7-carboxylate (0.22 g, 1.03 mmol) in EtOH (10 mL) was stirred at ambient temperature for 1 hour. The solvent was removed under reduced pressure. The residue was dissolved in DCM (10 mL) and iodo benzene diacetate (0.40 g, 1.24 mmol) was added. The mixture was stirred at ambient temperature for 1 hour. Ethyl acetate (20 mL) and saturated sodium bicarbonate (10 mL) were added. The organic layer was separated, washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue obtained was dissolved in THF (5 mL) and 2 N LiOH (5.15 mL, 10.30 mmol) was added. The mixture was stirred at ambient temperature for 6 hours. Ether (20 mL) was added. The aqueous layer was separated and acidified with saturated potassium hydrogen sulfate to about pH 3. The resulting solid was collected by filtration to give 2-(6-(1-((S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl)-2,2,2-trifluoroethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinoline-7-carboxylic acid (0.45 g, 78.5%) as a solid.

1. customThe solvent was removed under reduced pressure
2. dissolutionThe residue was dissolved in DCM (10 mL)
3. customThe organic layer was separated
4. washwashed with brine
5. dry with materialdried (sodium sulfate)
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe residue obtained
9. stirringThe mixture was stirred at ambient temperature for 6 hours
10. customThe aqueous layer was separated
11. filtrationThe resulting solid was collected by filtration