Dimethylformamide → 4-chloro-1H-pyrrolo[2,3-b]pyridine-5-carbaldehyde

Temperature

-78 °C

s-Butyllithium-hexane/cyclohexane solution (1.06 M, 27 mL, 29 mmol) was added to 4-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (5.74 g, 18.6 mmol) in tetrahydrofuran (50 mL) cooled to −78° C., and the reaction mixture was stirred for 1 hour. The reaction mixture was stirred with N,N-dimethylformamide (7.0 mL, 90 mmol) for another 1 hour and then with 4 M hydrogen chloride-1,4-dioxane solution (20 mL) for 30 minutes, and after addition of water, extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (15 mL) and stirred with trifluoroacetic acid (15 mL) for one day. The reaction mixture was concentrated under reduced pressure, diluted with water and neutralized with saturated aqueous sodium hydrogen carbonate, and the residue was collected by filtration and dried under reduced pressure. The crude product was mixed with ethyl acetate (20 mL) and hexane (20 mL), and the solid was collected by filtration, washed with hexane and dried under reduced pressure to give the title compound as a pale yellow solid (2.72 g, yield 81%).

1. extractionextracted with ethyl acetate
2. washThe organic layer was washed with saturated aqueous sodium chloride
3. dry with materialdried over anhydrous magnesium sulfate
4. concentrationconcentrated under reduced pressure
5. dissolutionThe resulting residue was dissolved in dichloromethane (15 mL)
6. stirringstirred with trifluoroacetic acid (15 mL) for one day
7. concentrationThe reaction mixture was concentrated under reduced pressure
8. additiondiluted with water and neutralized with saturated aqueous sodium hydrogen carbonate
9. filtrationthe residue was collected by filtration
10. customdried under reduced pressure
11. additionThe crude product was mixed with ethyl acetate (20 mL) and hexane (20 mL)
12. filtrationthe solid was collected by filtration
13. washwashed with hexane
14. customdried under reduced pressure

ORD record

ord-e4d3cb29a3644976bb09c5624cf84e4f

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09216999B2