Dicyclohexylcarbodiimide → 7-Bromo-3-chloro-1-methoxy-5',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,4'-[1,3]oxazin]-2'-amine

To a solution of 2-(5-amino-7-bromo-3-chloro-1-fluoro-5H-chromeno[2,3-c]pyridin-5-yl)ethanol (0.50 g, 1.338 mmol) in THF (10 mL) was added 4-nitrobenzoyl isothiocyanate (0.306 g, 1.472 mmol) and the reaction mixture was stirred at RT for 25 min. TEA (0.019 mL, 0.134 mmol) and 1,3-dicyclohexylcarbodiimide (0.304 g, 1.472 mmol) were added and the reaction mixture was heated at 70° C. for 1.5 h. The reaction mixture was allowed to warm to RT and concentrated under reduced pressure. The residue was dissolved in MeOH (15 mL) and potassium carbonate (0.555 g, 4.01 mmol) was added. The resulting mixture was stirred at rt overnight. The reaction mixture was concentrated under reduced pressure, washed with water and extracted with DCM. The combined organic layers were dried over Na2SO4 and the solvent was removed under reduced pressure. The residue was purified by chromatography (0-40% EtOAc/hexanes) to afford 7-bromo-3-chloro-1-methoxy-5′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,4′-[1,3]oxazin]-2′-amine (0.45 g, 1.096 mmol, 82% yield) as a yellow solid.

1. temperaturethe reaction mixture was heated at 70° C. for 1.5 h
2. temperatureto warm to RT
3. concentrationconcentrated under reduced pressure
4. dissolutionThe residue was dissolved in MeOH (15 mL)
5. stirringThe resulting mixture was stirred at rt overnight
6. concentrationThe reaction mixture was concentrated under reduced pressure
7. washwashed with water
8. extractionextracted with DCM
9. dry with materialThe combined organic layers were dried over Na2SO4
10. customthe solvent was removed under reduced pressure
11. customThe residue was purified by chromatography (0-40% EtOAc/hexanes)

ORD record

ord-dabfc14d79014cf487ff53f37fe71a4f

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08497264B2