Iodine → 4-(2-fluoro-4-nitrophenoxy)-3-iodo-1-methyl-1H-pyrazolo[3,4-b]pyridine

Temperature

50 °C

To a stirred solution of 4-(2-fluoro-4-nitrophenoxy)-1H-pyrazolo[3,4-b]pyridine (12.0 g, 43.8 mmol, prepared using the procedure described in Example 3, Step A) in DMF (100 mL) was added freshly ground (mortar/pestle) potassium hydroxide (7.37 g, 131 mmol) followed immediately by iodine (16.7 g, 65.6 mmol) under N2(g) at 25° C. The dark reaction was heated to 50° C. for 3 hours. One third of the reaction mixture volume was poured into a stirred solution of iodomethane (3.09 g, 21.7 mmol) in DMF (25 mL) at 0° C. under N2. The reaction was allowed to warm to 25° C. and stirred for 18 hours under N2. The mixture was diluted with CH2Cl2 (50 mL) and washed with a co-solvent of saturated aqueous Na2S2O3 (10 mL) and water (40 mL). The aqueous phase was extracted with 10% MeOH in CH2Cl2 (30 mL). The combined organic phases were washed with the Na2S2O3/water mixture followed by water, dried (Na2SO4), filtered, and concentrated in vacuo. The resulting residue was triturated with diethyl ether, and the solid filtered to afford the desired product (4.01 g, 62%).

1. additionwas added freshly
2. customThe dark reaction
3. temperatureto warm to 25° C.
4. washwashed with a co-solvent of saturated aqueous Na2S2O3 (10 mL) and water (40 mL)
5. extractionThe aqueous phase was extracted with 10% MeOH in CH2Cl2 (30 mL)
6. washThe combined organic phases were washed with the Na2S2O3/water mixture
7. dry with materialdried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe resulting residue was triturated with diethyl ether
11. filtrationthe solid filtered

ORD record

ord-887e29fb6d1646a8a41a93bc5cef5f96

Source dataset

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07723330B2