反应详情

To a solution of ethyl 2-(2-((4-(tert-butoxycarbonyl)piperazin-1-yl)methyl)-4-cyclopentyl-5-(methoxycarbonyloxy)phenylcarbamoyl)-6-cyano-2H-benzo[b][1,4]oxazine-4(3H)-carboxylate (15 mg, 0.022 mmol) in dichloromethane (500 μL) was added TFA (3 μL, 0.04 mmol) and the reaction was stirred overnight at room temperature. The reaction was quenched with aqueous NaHCO3 and the layers separated. The aqueous layer was extracted with dichloromethane, dried over MgSO4, filtered and concentrated. The crude product was dissolved in methanol and 1 M NaOH and the reaction was heated at reflux for 5 min. The reaction was quenched with 1 M HCl and the aqueous layer was extracted with dichloromethane. The organic layer was dried over MgSO4, filtered and concentrated. Purification by HPLC (10-99% CH3CN/0.05% TFA) provided 6-cyano-N-[4-cyclopentyl-5-hydroxy-2-(piperazin-1-ylmethyl)phenyl]-3,4-dihydro-2H-1,4-benzoxazine-2-carboxamide (3 mg, 24% yield). LC/MS m/z 462.5 [M+H]+.

1. customThe reaction was quenched with aqueous NaHCO3
2. customthe layers separated
3. extractionThe aqueous layer was extracted with dichloromethane
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. dissolutionThe crude product was dissolved in methanol
8. temperature1 M NaOH and the reaction was heated
9. temperatureat reflux for 5 min
10. customThe reaction was quenched with 1 M HCl
11. extractionthe aqueous layer was extracted with dichloromethane
12. dry with materialThe organic layer was dried over MgSO4
13. filtrationfiltered
14. concentrationconcentrated
15. customPurification by HPLC (10-99% CH3CN/0.05% TFA)