4-Fluoroaniline → N-(2,5-Difluoro-4-{[2-({[(3S)-3-hydroxypyrrolidin-1-yl]carbonyl}amino)pyridin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

4-(4,6-Dimethoxy[1,3,5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (365 mg) was added to a mixture of 1-[({2,5-difluoro-4-[(2-{[((S)-3-hydroxypyrrolidin-1-yl)carbonyl]amino}pyridin-4-yl)oxy]phenyl}amino)carbonyl]cyclopropanecarboxylic acid triethylamine salt (175 mg), 4-fluoroaniline (0.0587 ml) and tetrahydrofuran (4.0 ml) at room temperature under a nitrogen atmosphere, and the mixture was stirred for 68 hours and 30 minutes. A saturated aqueous solution of sodium hydrogencarbonate (10 ml) was added to the mixture and stirred, and the mixture was partitioned after the addition of ethyl acetate and tetrahydrofuran (1:1) (40 ml) and water (30 ml). The organic layer was washed with brine (20 ml), and dried over anhydrous magnesium sulfate. The desiccant was removed by filtration, and the filtrate was concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=10:1). The fractions containing the target compound were concentrated under reduced pressure to give the title compound (128.5 mg, 75%) as a white solid.

1. stirringstirred
2. customthe mixture was partitioned
3. additionafter the addition of ethyl acetate and tetrahydrofuran (1:1) (40 ml) and water (30 ml)
4. washThe organic layer was washed with brine (20 ml)
5. dry with materialdried over anhydrous magnesium sulfate
6. customThe desiccant was removed by filtration
7. concentrationthe filtrate was concentrated under reduced pressure
8. customThe resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent
9. additionThe fractions containing the target compound
10. concentrationwere concentrated under reduced pressure

ORD 기록

ord-4e64a2c35d8a432c9a17aad241874811

출처 데이터셋

uspto-grants-2010_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07790885B2