Water → HCID 178490903, compound

HRID 387601Notes

Reaction equation

HRID 387601 reaction equation
C1C(=O)N([Cl:8])C(=O)C1.[CH3:9][O:10][C:11]1[CH:27]=[CH:26][C:14]([CH2:15][N:16]2[C:20]3[N:21]=[CH:22][CH:23]=[C:24]([OH:25])[C:19]=3[CH:18]=[N:17]2)=[CH:13][CH:12]=1.O>CN(C=O)C>[Cl:8][C:23]1[CH:22]=[N:21][C:20]2[N:16]([CH2:15][C:14]3[CH:13]=[CH:12][C:11]([O:10][CH3:9])=[CH:27][CH:26]=3)[N:17]=[CH:18][C:19]=2[C:24]=1[OH:25]

Participants

5

Reactant 3

HCID 962WaterHCID 31398Chlorosuccinimide2×HCID 178490904HCID 178490904, compound

Product 1

HCID 178490903HCID 178490903, compoundYield 13.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

NCS (1.57 g, 11.8 mmol) was added in one portion to a solution of 1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-ol (3.00 g, 11.8 mmol) in DMF (30 mL) at room temperature. The mixture was stirred at 60° C. for 1 hour and then cooled to room temperature. After 18 hours, an additional lot of NCS (0.5 eq.) was added to the reaction mixture and stirred at room temperature for an additional 48 hours. The reaction mixture was poured into water (150 mL) and extracted with EtOAc (3×50 mL). The combined organic layers were washed once with water (50 mL), dried (MgSO4), filtered, and concentrated in vacuo. The crude material was purified by flash chromatography on silica gel (Biotage Flash 40M+) eluting with 2% MeOH/CH2Cl2 to provide 5-chloro-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-ol (466 mg, 1.61 mmol, 13.7% yield). LCMS (APCI+) m/z 290 (M+H)+.

Workup

  1. temperaturecooled to room temperature
  2. waitAfter 18 hours
  3. stirringstirred at room temperature for an additional 48 hours
  4. extractionextracted with EtOAc (3×50 mL)
  5. washThe combined organic layers were washed once with water (50 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified by flash chromatography on silica gel (Biotage Flash 40M+)
  10. washeluting with 2% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-7e1ed013231c4fa2a1e9ae1eccf05844
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

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