Phosphorus oxychloride → 8-Bromoimidazo[1,5-a]pyridine

Temperature

0 °C

A suspension of N-[(3-bromopyridin-2-yl)methyl]formamide (312.0 mg, 1.451 mmol) in toluene (7.0 mL) was charged with phosphorus oxychloride (0.50 mL, 5.4 mmol) and then refluxed for 1 h. The mixture was concentrated. The residue was cooled to 0° C. and water was added slowly. To the cooled aqueous suspension, aqueous ammonium hydroxide was added until the pH was basic, and the mixture was then extracted with ethyl acetate. The organic fraction was washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated. Purification of the residue by ISCO chromatography (100% ethyl acetate) afforded 180.5 mg (63%) of the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 8.51 (d, J=0.51 Hz, 1H), 8.39 (td, J=0.88, 7.07 Hz, 1H), 7.38 (t, J=0.88 Hz, 1H), 7.12 (d, J=7.07 Hz, 1H), 6.60 (dd, J=6.90, 6.90 Hz, 1H); MS (ESI): 197.05, 198.99 [M+H]+; HPLC tR=2.86 min (ZQ3: polar—5 min).

1. temperaturerefluxed for 1 h
2. concentrationThe mixture was concentrated
3. additionwater was added slowly
4. additionTo the cooled aqueous suspension, aqueous ammonium hydroxide was added until the pH
5. extractionthe mixture was then extracted with ethyl acetate
6. washThe organic fraction was washed with brine
7. dry with materialdried over anhydrous Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customPurification of the residue by ISCO chromatography (100% ethyl acetate)

ORD record

ord-3799ad366fe344b2b98d7a48abc0df62

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08378104B2