Morpholine → N-(4-(4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)-2,5-difluorophenoxy)pyridin-2-yl)morpholine-4-carboxamide

To a suspension of N-(4-((2-aminopyridin-4-yl)oxy)-2,5-difluorophenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (250 mg, 0.56 mmol) and Et3N (0.25 mL, 1.68 mmol) in THF (10.0 mL) was added phenyl carbonochloridate (0.25 mL, 1.68 mmol). The mixture was stirred at rt for 2 hours, then morpholine (0.35 mL, 3.46 mmol) was added. The reaction mixture was stirred rt for 24 hours and partitioned between aq NH4Cl (40 mL) and DCM (40 mL). The organic phase was separated and the aqueous phase was extracted with DCM (40 mL×3). The combined organic phases was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc/PE (v/v)=4/1) to give the title compound as a white solid (70 mg, 21%).

1. stirringThe reaction mixture was stirred rt for 24 hours
2. custompartitioned between aq NH4Cl (40 mL) and DCM (40 mL)
3. customThe organic phase was separated
4. extractionthe aqueous phase was extracted with DCM (40 mL×3)
5. dry with materialThe combined organic phases was dried over anhydrous Na2SO4
6. concentrationconcentrated in vacuo
7. customThe residue was purified by a silica gel column chromatography (EtOAc/PE (v/v)=4/1)

ORDレコード

ord-ef362049e75f403ca3ea32cdcae8b1d7

出典データセット

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08969388B1