反应详情

From Example 55. To a solution of cyclopentyl N-(5-{4-[6-amino-5-(4-fluorobenzoyl)-2-oxopyridin-1(2H)-yl]-3,5-difluorophenoxy}pentyl)-L-leucinate (33 mg, 0.05 mmol) in THF (1 ml) and water (1 ml) was added LiOH (25 mg, 1.05 mmol, 20 eq). The mixture was stirred at room temperature for 16 hours, before being heated at 80° C. for 10 hours. The mixture was concentrated under reduced pressure and water (5 ml) added. The pH was adjusted to 7 using 1M HCl and the aqueous layer extracted with 1-butanol (3×5 ml). The combined organic extracts were concentrated under reduced pressure. The solid residue was triturated with Et2O, collected by filtration and purified by preparative HPLC to provide the title compound as a white solid as the mono-TFA salt (7 mg, 24% yield). LC/MS: m/z 560 [M+H]+. 1H NMR (300 MHz, DMSO-d6) δ: 7.62-7.51 (3H, m), 7.34 (2H, m), 7.05 (2H, m), 5.72 (1H, d, J=9.8 Hz), 4.09 (2H, t, J=5.7 Hz), 3.23 (1H, m), 2.80 (2H, m), 1.79-1.43 (9H, m), 0.89 (6H, t, J=6.7 Hz).

1. temperaturebefore being heated at 80° C. for 10 hours
2. concentrationThe mixture was concentrated under reduced pressure and water (5 ml)
3. additionadded
4. extractionthe aqueous layer extracted with 1-butanol (3×5 ml)
5. concentrationThe combined organic extracts were concentrated under reduced pressure
6. customThe solid residue was triturated with Et2O
7. filtrationcollected by filtration
8. custompurified by preparative HPLC