Dimethylformamide → 5-(3-{(5-Fluoro-8-methoxychroman-6-yl)-[4-(5-trifluoromethyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)-1H-pyrazole-4-carboxylic acid ethyl ester

온도

85 °C

To 5 ml of a DMF solution containing 160 mg of [2-(5-fluoro-8-methoxychroman-6-yl)-2-[4-(5-trifluoromethyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene]carbamic acid methyl ester, 87 mg of 3-hydrazino-1H-pyrazole-4-carboxylic acid ethyl ester bishydrochloride (Example (157b)) and 0.124 ml of triethylamine were added. The resulting mixture was stirred at 85° C. for 16 hours under a nitrogen atmosphere. The reaction mixture was concentrated. The residue was dissolved in 8 ml of methanol and 0.068 ml of acetic acid, and then 187 mg of sodium cyanotrihydroborate was added thereto. The mixture was stirred at room temperature for 15 hours, and then 100 ml of ethyl acetate and 50 ml of water were added thereto. The organic layer was washed with 50 ml of water and then with 50 ml of saturated brine and was dried over anhydrous magnesium sulfate. The desiccating agent was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by NAM silica gel column chromatography (methanol-ethyl acetate) to give the title compound (39 mg).

1. additionwere added
2. concentrationThe reaction mixture was concentrated
3. dissolutionThe residue was dissolved in 8 ml of methanol
4. addition0.068 ml of acetic acid, and then 187 mg of sodium cyanotrihydroborate was added
5. stirringThe mixture was stirred at room temperature for 15 hours
6. addition100 ml of ethyl acetate and 50 ml of water were added
7. washThe organic layer was washed with 50 ml of water
8. dry with materialwith 50 ml of saturated brine and was dried over anhydrous magnesium sulfate
9. customThe desiccating agent was removed by filtration
10. concentrationthe filtrate was concentrated under reduced pressure
11. customThe residue was purified by NAM silica gel column chromatography (methanol-ethyl acetate)

ORD 기록

ord-dbd671742f9c4c15aac4537a5f5ad92f

출처 데이터셋

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07816522B2