Triethylamine → 3-[5-chloro-4-(6-fluoro-pyridin-2-ylmethoxy)-2-methyl-6-oxo-6H-pyrimidin-1-yl]-N-methoxy-4,N-dimethyl-benzamide

To a solution of 3-[5-chloro-4-(6-fluoro-pyridin-2-ylmethoxy)-2-methyl-6-oxo-6H-pyrimidin-1-yl]-4-methyl-benzoic acid methyl ester from Step B (180 mg, 0.43 mmol) in tetrahydrofuran (2 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 give a yellow solid which was used without additional purification. To a solution of the crude acid in tetrahydrofuran (2 mL) was added 1,1′-carbonyldiimidazole (105 mg, 0.65 mmol). After stirring at ambient temperature for one hour, N,N-dimethylhydroxylamine HCl (63 mg, 0.65 mmol) and triethylamine (0.12 mL, 0.86 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 (85 mg, 44%). MS (M+H): 447

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 give a yellow solid which
8. customwas used without additional purification
9. stirringAfter stirring 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

ORD 기록

ord-65d92ffa3c454fcdb46cc6b3c0c31e58

출처 데이터셋

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09056110B2