Water → 1-[8-Chloro-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl]-2-propyn-1-one

Temperature

-78 °C

To a cold (−78° C.) suspension of 8-chloro-2-(4-fluorophenyl)imidazo[1,2-α]pyridine-3-carbaldehyde (0.94 g, 3.42 mmol) in tetrahydrofuran (20 mL) was added ethynylmagnesium bromide (15 mL, 0.5 M in tetrahydrofuran, 7.5 mmol) dropwise. The reaction mixture was stirred at −78° C. for 1 hour, then at 0° C. for 2 hours. The resulting solution was poured into water and extracted with ethyl acetate. The organic layer was washed with water and brine and the combined organics were dried over magnesium sulfate. Filtration and concentration gave a white solid. This solid was dissolved in dichlormethane (60 mL) and to this solution was added manganese dioxide (10 g, 115 mmol). The reaction mixture was stirred at room temperature for 1 hour. The suspension was filtered through a pad of Celite and the filtrate was concentrated and purified by silica gel chromatography (1:1 hexanes:ethyl acetate) to give 1-[8-chloro-2-(4-fluorophenyl)imidazo[1,2-α]pyridin-3-yl]-2-propyn-1-one (0.56 g, 55%) as a white solid. 1H NMR (CDCl3) δ 9.67 (d, 1H), 7.68 (m, 3H), 7.12 (m, 3H), 2.89 (s, 1H); 19F NMR (CDCl3) δ −111.6; MS m/z 299 (M+1).

1. waitat 0° C. for 2 hours
2. extractionextracted with ethyl acetate
3. washThe organic layer was washed with water and brine
4. dry with materialthe combined organics were dried over magnesium sulfate
5. filtrationFiltration and concentration
6. customgave a white solid
7. stirringThe reaction mixture was stirred at room temperature for 1 hour
8. filtrationThe suspension was filtered through a pad of Celite
9. concentrationthe filtrate was concentrated
10. custompurified by silica gel chromatography (1:1 hexanes:ethyl acetate)

ORD record

ord-022b207ca15149c999dab7ad877bc35b

Source dataset

uspto-grants-2007_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07186714B2