Acetic Acid → 6-fluoro-7-iodo-1H-pyrazolo[4,3-b]pyridine

Temperature

40 °C

6-Fluoro-7-iodo-1H-pyrazolo[4,3-b]pyridin-3-amine (250 mg) was combined with water (4 mL) and AcOH (6 mL) was heated to 40° C. until the solution became clear. The reaction mixture was then cooled to 0° C. and a solution of sodium nitrite (137 mg) in water (1 mL) was added dropwise over about 30 minutes. The reaction mixture was then warmed to room temperature, and stirred for 16 hours. The reaction mixture was again cooled to 0° C. and stirred for another 0.5 hour to give a solid which was collected by filtration, and washed with cold water. The solid were suspended in diluted HI (0.25 mL 50% HI diluted with water to 2.75 mL) and dimethoxyethane (6.5 mL) and the reaction mixture was heated to 80° C. for 3 hours, then cooled to room temperature, neutralized with Na2CO3 solution, and then extracted with ethyl acetate (60 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure to give a residue which was purified by silica gel chromatography eluting with petroleum ether-ethyl acetate (5:1) to afford the title compound (120 mg, 50.6% yield) as a light yellow solid. 1H-NMR (400 MHz, DMSO-d6) δ ppm 13.77 (s, 1H) 8.50 (s, 1H) 8.40 (s, 1H). MS [M+H] found 264.0.

1. temperatureThe reaction mixture was then cooled to 0° C.
2. temperatureThe reaction mixture was then warmed to room temperature
3. temperatureThe reaction mixture was again cooled to 0° C.
4. stirringstirred for another 0.5 hour
5. customto give a solid which
6. filtrationwas collected by filtration
7. washwashed with cold water
8. temperaturedimethoxyethane (6.5 mL) and the reaction mixture was heated to 80° C. for 3 hours
9. temperaturecooled to room temperature
10. extractionextracted with ethyl acetate (60 mL)
11. dry with materialThe organic layer was dried over anhydrous Na2SO4
12. filtrationfiltered
13. customevaporated under reduced pressure
14. customto give a residue which
15. customwas purified by silica gel chromatography
16. washeluting with petroleum ether-ethyl acetate (5:1)

ORD record

ord-2e7a6a74af2545288299599c78b26645

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09073918B2