1,2-Difluoro-4-nitrobenzene → 1-(4-methoxybenzyl)-4-(2-fluoro-4-nitrophenoxy)-1H-pyrazolo[3,4-b]pyridine

HRID 2241180Notes

Reaction equation

HRID 2241180 reaction equation
[CH3:1][O:2][C:3]1[CH:19]=[CH:18][C:6]([CH2:7][N:8]2[C:12]3[N:13]=[CH:14][CH:15]=[C:16]([OH:17])[C:11]=3[CH:10]=[N:9]2)=[CH:5][CH:4]=1.F[C:21]1[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][C:22]=1[F:30]>CC(N(C)C)=O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:21]4[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][C:22]=4[F:30])=[C:11]3[CH:10]=[N:9]2)=[CH:18][CH:19]=1

Participants

4

Reactant 2

HCID 1230531,2-Difluoro-4-nitrobenzeneHCID 178490904HCID 178490904, compound

Product 1

HCID 672207711-(4-methoxybenzyl)-4-(2-fluoro-4-nitrophenoxy)-1H-pyrazolo[3,4-b]pyridine

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

A stirred mixture of 1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-ol (22.00 g, 86.18 mmol) cesium carbonate (28.08 g, 86.18 mmol), 1,2-difluoro-4-nitrobenzene (13.71 g, 86.18 mmol) and DMA (100 mL) was heated to 100° C. for 1 hour. After cooling to room temperature, the mixture was partitioned between DCM (500 mL) and water (500 mL). The phases were separated, and the organic phase washed with water (3×200 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The resulting residue was triturated with diethyl ether (100 mL) and hexanes (200 mL) co-solvent, and the resulting beige powder was filtered. A second crop was obtained after cooling in a −10° C. freezer overnight. The two crops were combined (28 g, 82%). 1H NMR (400 MHz, CDCl3) δ 8.45 (d, J=5.5 Hz, 1H), 8.16 (m, 2H), 7.86 (s, 1H), 7.39 (m, 1H), 7.35 (d, J=8.6 Hz, 2H), 6.84 (d, J=8.2 Hz, 2H), 6.48 (d, J=5.5 Hz, 1H), 5.65 (s, 2H), 3.76 (s, 3H). 19F NMR (376 MHz, CDCl3) δ −124.2 (m).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe mixture was partitioned between DCM (500 mL) and water (500 mL)
  3. customThe phases were separated
  4. washthe organic phase washed with water (3×200 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was triturated with diethyl ether (100 mL) and hexanes (200 mL) co-solvent
  9. filtrationthe resulting beige powder was filtered
  10. customA second crop was obtained
  11. temperatureafter cooling in a −10° C. freezer overnight

Sources & evidence

ORD record
ord-744509c9964a4e9188f354f84f44d6c2
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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