反应详情

To a solution of 3-[5-bromo-2-methyl-4-(6-methyl-pyridin-2-ylmethoxy)-6-oxo-6H-pyrimidin-1-yl]-4-methyl-benzoic acid methyl ester from Step B (148 mg, 0.31 mmol) in tetrahydrofuran (2 mL) was added 1N sodium hydroxide (1 mL) and the solution stirred at ambient temperature for three hours. The solution was concentrated in vacuo and the aqueous residue 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 provide a yellow oil used without any additional purification. To a solution of the crude acid in tetrahydrofuran (3 mL) was added 1,1′-carbonyldiimidazole (75 mg, 0.46 mmol). After stifling at ambient temperature for one hour, N,N-dimethylhydroxylamine HCl (45 mg, 0.46 mmol) and triethylamine (0.09 mL, 0.62 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 yellow oil (60 mg, 40%). MS (M, M+2): 487, 489

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
7. customto provide a yellow oil
8. customused without any additional purification
9. waitAfter stifling at ambient temperature for one hour
10. stirringto stir for eighteen hours
11. customThe solution was partitioned between ethyl acetate and water
12. washThe organic layer was washed with saturated sodium bicarbonate, water, and brine
13. dry with materialdried over magnesium sulfate
14. filtrationThe slurry was filtered
15. concentrationconcentrated