反应详情

温度

50 °C

To a solution of methyl 2-{[(2,4-difluorophenyl)methyl]oxy}-5-(4-morpholinylcarbonyl)benzoate acid (may be prepared as described in Description 110; 100 mg, 0.26 mmol) in tetrahydrofuran (4 ml) was added lithium hydroxide (26 mg, 109 mmol) and water (1 ml). The mixture was heated at 50° C. for one hour, cooled and 2 M hydrochloric acid (0.54 ml, 1.09 mmol) was added. The solvent was removed in vacuo and the residue was redissolved in N,N-dimethylformamide (5 ml). 3-Methyl-4-isoxazolamine hydrochloride (42.8 mg, 0.32 mmol), 1-hydroxy-7-azabenzotriazole (39.7 mg, 0.29 mmol), diisopropylethylamine (0.09 ml, 0.53 mmol) and EDC (76 mg, 0.40 mmol) were added. The solution was stirred for 18 hours. Water (3 ml) was added and a pale brown solid precipitated which was filtered. Recrystallisation with 1:1 methanol/DMSO yielded the title compound as a white solid. 9.5 mg.

1. temperaturecooled
2. customThe solvent was removed in vacuo
3. dissolutionthe residue was redissolved in N,N-dimethylformamide (5 ml)
4. customa pale brown solid precipitated which
5. filtrationwas filtered
6. customRecrystallisation with 1:1 methanol/DMSO