Diisopropylethylamine → N-((2S)-1-((2-(5-hydroxypyridin-2-yl)[1,3]oxazolo[4,5-c]pyridin-6-yl)oxy)propan-2-yl)acetamide

To a solution of N-((2S)-1-((4-chloro-5-nitropyridin-2-yl)oxy)propan-2-yl)acetamide (1.80 g) in ethanol (20 mL) were added iron powder (1.84 g) and iron(III) chloride (1.07 g), and the mixture was stirred with heating under reflux for 1 hr. The reaction mixture was filtered, and the filtrate was diluted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give N-((2S)-1-((5-amino-4-chloropyridin-2-yl)oxy)propan-2-yl)acetamide (1.46 g). To a solution of N-((2S)-1-((5-amino-4-chloropyridin-2-yl)oxy)propan-2-yl)acetamide (830 mg) and 5-(benzyloxy)pyridine-2-carboxylic acid (781 mg), diisopropylethylamine (1.19 mL) in DMF (10 mL) was added HATU (1.49 g), and the mixture was stirred at room temperature for 30 min. The precipitated solid was washed with ethyl acetate-hexane. A suspension of the obtained solid, potassium carbonate (1.22 g) and copper(I) iodide (84.0 mg) in DMF (10 mL) was stirred at 160° C. for 1.5 hr. The reaction mixture was subjected to silica gel chromatography (NH, ethyl acetate), and washed with saturated brine, and the solvent was evaporated. The obtained solid was washed with ethyl acetate/hexane. A mixture of the obtained solid, 10% palladium/carbon (containing water (50%), 200 mg) and THF (10 mL) was stirred at room temperature for 30 min under a hydrogen atmosphere. The catalyst was removed by filtration, and the obtained filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/methanol) to give the title compound (37.4 mg).

1. washThe precipitated solid was washed with ethyl acetate-hexane
2. additionA suspension of the obtained solid, potassium carbonate (1.22 g) and copper(I) iodide (84.0 mg) in DMF (10 mL)
3. stirringwas stirred at 160° C. for 1.5 hr
4. washwashed with saturated brine
5. customthe solvent was evaporated
6. washThe obtained solid was washed with ethyl acetate/hexane
7. additionA mixture of the obtained solid, 10% palladium/carbon (containing water (50%), 200 mg) and THF (10 mL)
8. stirringwas stirred at room temperature for 30 min under a hydrogen atmosphere
9. customThe catalyst was removed by filtration
10. concentrationthe obtained filtrate was concentrated under reduced pressure
11. customThe residue was purified by silica gel column chromatography (ethyl acetate/methanol)

ORD record

ord-d2513ade52fd472dbcd0026344ccc73b

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09133129B2