Cesium carbonate → 1-(4-methoxybenzyl)-4-(5-chloro-2-methyl-4-nitrophenoxy)-1H-pyrazolo[3,4-b]pyridine

HRID 2241278Notes

Reaction equation

HRID 2241278 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.[Cl:20][C:21]1[CH:26]=[C:25](F)[C:24]([CH3:28])=[CH:23][C:22]=1[N+:29]([O-:31])=[O:30].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[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:25]4[CH:26]=[C:21]([Cl:20])[C:22]([N+:29]([O-:31])=[O:30])=[CH:23][C:24]=4[CH3:28])=[C:11]3[CH:10]=[N:9]2)=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 875934-Chloro-2-fluoro-5-nitrotolueneHCID 178490904HCID 178490904, compound

Product 1

HCID 685114941-(4-methoxybenzyl)-4-(5-chloro-2-methyl-4-nitrophenoxy)-1H-pyrazolo[3,4-b]pyridineYield 9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

A stirred mixture of 1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-ol (255 g, 999 mmol, prepared using the procedure described in Example 1, Step B), 1-chloro-5-fluoro-4-methyl-2-nitrobenzene (94.7 g, 499 mmol), cesium carbonate (325 g, 1.0 mol) and DMF (2 L) was heated to 95° C. for 6 hours. The reaction was cooled to ambient temperature and partitioned between EtOAc and water. The phases were filtered and then separated. The aqueous phase was re-extracted with EtOAc. The combined organic phases were washed with water, brine, dried (Na2SO4), filtered, and concentrated in vacuo. The crude was purified by Biotage Flash 75 L chromatographic system, eluting with 5% EtOAc/hexanes (12 L), 10% EtOAc/hexanes (6 L), 20% EtOAc/hexanes (6 L), then 30% EtOAc/hexanes (6 L). The product was obtained as a viscous oil (42 g, 9%).

Workup

  1. customprepared
  2. temperatureThe reaction was cooled to ambient temperature
  3. custompartitioned between EtOAc and water
  4. filtrationThe phases were filtered
  5. customseparated
  6. extractionThe aqueous phase was re-extracted with EtOAc
  7. washThe combined organic phases were washed with water, brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude was purified by Biotage Flash 75 L chromatographic system
  12. washeluting with 5% EtOAc/hexanes (12 L), 10% EtOAc/hexanes (6 L), 20% EtOAc/hexanes (6 L)

Sources & evidence

ORD record
ord-71a821d91d7a4f01911fb475b3d27124
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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