Tetrahydrofuran → (S)-3-bromo-7-(pyrimidin-5-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

Temperature

110 °C

A sealable tube was charged with (S)-3-bromo-7-iodo-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (2.000 g, 4.37 mmol), pd(ph3p)4 (0.504 g, 0.437 mmol), pyrimidin-5-ylboronic acid (0.568 g, 4.58 mmol) and THF (21.83 mL, 4.37 mmol). The mixture was flushed with Ar then a solution of potassium carbonate (1.5 M) (5.82 mL, 8.73 mmol) was added. The reaction was heated at 110° C. for 2 hours before being diluted with water 50 mL and poured into a separatory funnel containing ethyl acetate 50 mL. The layers were separated and the aqueous layer was extracted with ethyl acetate 3×100 mL. The aqeuous layer was then extracted with DCM (3×100 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to provide a brown oil that was purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (80 g), 0-10% methanol in methylenechloride with 0.1% ammonium hydroxide) to provide (S)-3-bromo-7-(pyrimidin-5-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine as a light yellow foam.

1. customThe mixture was flushed with Ar
2. additionpoured into a separatory funnel
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with ethyl acetate 3×100 mL
5. extractionThe aqeuous layer was then extracted with DCM (3×100 mL)
6. washThe combined organic layers were washed with brine
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customto provide a brown oil that
11. customwas purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (80 g), 0-10% methanol in methylenechloride with 0.1% ammonium hydroxide)

ORD record

ord-520f13c0bd4144b2b24c702b97f189c4

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08426447B2