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

To a suspension of N-(4-((2-aminopyridin-4-yl)oxy)-2-chloro-5-fluorophenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (234 mg, 0.5 mmol) and Et3N (0.1 mg, 1 mmol) in THF (5 mL) was added phenyl chloroformate (0.16 mg, 1 mmol). The mixture was stirred at rt for 2 hours, then morpholine (0.44 mL, 5 mmol) was added. The reaction mixture was stirred rt for 24 hours, then partitioned between aq NH4Cl (30 mL) and DCM (30 mL). The organic phase was separated and the aqueous phase extracted with DCM (30 mL×3). The combined organic phases were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (DCM/CH3OH (v/v)=50/1) to give the title compound as a white solid (145 mg, 49.9%).

1. stirringThe reaction mixture was stirred rt for 24 hours
2. custompartitioned between aq NH4Cl (30 mL) and DCM (30 mL)
3. customThe organic phase was separated
4. extractionthe aqueous phase extracted with DCM (30 mL×3)
5. dry with materialThe combined organic phases were dried over anhydrous Na2SO4
6. concentrationconcentrated in vacuo
7. customThe residue was purified by a silica gel column chromatography (DCM/CH3OH (v/v)=50/1)

ORDレコード

ord-645bca6add15430a9882b225259be6c1

出典データセット

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08969388B1