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

To a suspension of N-(4-((2-aminopyridin-4-yl)oxy)-2,3-difluorophenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (224 mg, 0.50 mmol) in THF (3 mL) was added Et3N (0.138 mL, 0.99 mmol), followed by adding phenyl carbonochloridate (0.125 mL, 1.00 mmol) dropwise. The reaction mixture was stirred at rt for 2 hours, then morpholine (0.4 mL, 5.00 mmol) was added. The mixture was stirred at rt for 36 hours, then quenched with saturated NH4Cl aqueous solution (20 mL) and CH2Cl2 (20 mL). The resulted mixture was stirred at rt for 10 minutes and extracted with CH2Cl2 (20 mL×3). The combined organic phases were washed with brine (20 mL×3), dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc/PE (v/v)=20/1) to give the title compound as an orange solid (148 mg, 52.5%).

1. stirringThe mixture was stirred at rt for 36 hours
2. customquenched with saturated NH4Cl aqueous solution (20 mL) and CH2Cl2 (20 mL)
3. stirringThe resulted mixture was stirred at rt for 10 minutes
4. extractionextracted with CH2Cl2 (20 mL×3)
5. washThe combined organic phases were washed with brine (20 mL×3)
6. dry with materialdried over anhydrous Na2SO4
7. concentrationconcentrated in vacuo
8. customThe residue was purified by a silica gel column chromatography (EtOAc/PE (v/v)=20/1)

ORD record

ord-7efa50731daa436596664fe50a100360

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08969388B1