反应详情

To a solution of 3-[5-chloro-4-(4-fluoro-benzyloxy)-2-methyl-6-oxo-6H-pyrimidin-1-yl]-4-methyl-benzoic acid methyl ester from Step A (63 mg, 0.15 mmol) in tetrahydrofuran (1 mL) was added 1N sodium hydroxide (1 mL) and the solution was stirred at ambient temperature for eighteen hours. The solution was concentrated in vacuo and the aqueous residue was acidified to pH=2 using 1M HCl. The solution was extracted with ethyl acetate, washed with water and dried over magnesium sulfate. The slurry was filtered and concentrated to an orange oil used without any additional purification. To a solution of the crude acid in tetrahydrofuran (2 mL) was added 1,1′-carbonyldiimidazole (37 mg, 0.23 mmol). After stifling at ambient temperature for one hour, N,N-dimethylhydroxylamine HCl (22 mg, 0.23 mmol) and triethylamine (0.04 mL, 0.30 mmol) were added. The solution continued to stir for eighteen hours. The solution was partitioned between ethyl acetate and water. The organic layer was washed with saturated sodium bicarbonate, water, and brine and dried over magnesium sulfate. The slurry was filtered and concentrated to provide the amide as a colorless oil (60 mg, 90%). MS (M+H): 446

1. concentrationThe solution was concentrated in vacuo
2. extractionThe solution was extracted with ethyl acetate
3. washwashed with water
4. dry with materialdried over magnesium sulfate
5. filtrationThe slurry was filtered
6. concentrationconcentrated to an orange oil
7. customused without any additional purification
8. stirringto stir for eighteen hours
9. customThe solution was partitioned between ethyl acetate and water
10. washThe organic layer was washed with saturated sodium bicarbonate, water, and brine
11. dry with materialdried over magnesium sulfate
12. filtrationThe slurry was filtered
13. concentrationconcentrated