Cesium carbonate → N-(4-(4-amino-2,5-difluorophenoxy)pyridin-2-yl)cyclopropanecarboxamide

A mixture of Example A2 (100 mg, 0.39 mmol), cyclopropanecarboxamide (100 mg, 1.17 mmol), Xantphos [4,5-bis(diphenylphosphino)-9,9-dimethylxanthene] (23 mg, 0.039 mmol), Cs2CO3 (254 mg, 0.78 mmol) and Pd2(dba)3 (22 mg, 0.023 mmol) in dioxane (10 mL) was heated at 100° C. for 2 hours. The mixture was cooled to RT and filtered to remove inorganic salts. The filtrate was concentrated under vacuum. The residue was diluted with water (100 mL) and extracted with EtOAc (3×100 mL). The combined organics were washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by silica gel chromatography to afford N-(4-(4-amino-2,5-difluorophenoxy)pyridin-2-yl)cyclopropanecarboxamide (56 mg, 47% yield). MS (ESI): m/z 306.1 (M+H+).

1. filtrationfiltered
2. customto remove inorganic salts
3. concentrationThe filtrate was concentrated under vacuum
4. additionThe residue was diluted with water (100 mL)
5. extractionextracted with EtOAc (3×100 mL)
6. washThe combined organics were washed with brine
7. dry with materialdried over Na2SO4
8. concentrationconcentrated in vacuo
9. customThe crude product was purified by silica gel chromatography

ORD record

ord-5e01f8c1385942eab12f25d680500326

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08921565B2