Ethyl Acetate → Ethyl [3-(bromomethyl)-1H-pyrazolo[3,4-b]pyridin-1-yl]acetate

HRID 503868Notes

Reaction equation

HRID 503868 reaction equation
C(OCC[N:7]1[C:11]2=[N:12][CH:13]=[CH:14][CH:15]=[C:10]2[C:9]([CH3:16])=[N:8]1)(=O)C.C1C(=O)N([Br:24])C(=O)C1.[CH3:25][CH2:26][O:27][C:28]([CH3:30])=[O:29]>C(Cl)(Cl)(Cl)Cl>[CH2:26]([O:27][C:28](=[O:29])[CH2:30][N:7]1[C:11]2=[N:12][CH:13]=[CH:14][CH:15]=[C:10]2[C:9]([CH2:16][Br:24])=[N:8]1)[CH3:25]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 67184N-bromobutanimideHCID 67103879HCID 67103879, compound

Product 1

HCID 57642772Ethyl [3-(bromomethyl)-1H-pyrazolo[3,4-b]pyridin-1-yl]acetate

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Procedure

A mixture of (3-methyl-pyrazolo[3,4-b]pyridine-1-yl)ethyl acetate (2.5 Mmol, 1 eq.), NBS (3.0 Mmol, 1.2 eq.), and benzoly peroxide (0.05 Mmol, 0.02 eq.) in 10 mL of CCl4 was refluxed for 1.5 h. The resultant mixture was cooled to rt, and diluted with 500 mL of EtOAc. The resultant solution was then washed with 100 mL of sat. sodium bicarbonate aqueous solution, brine solution, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography (20% EtOAc in hexane to 35% EtOAc in hexane) to provide 450.2 Mg of the desired product: HPLC retention time=2.50 minutes (Agilent Zorbax SB-C18, 2.1×50 Mm, 5μ, 35° C.) using 1 mL/min flow rate, a 2.5 minute gradient of 0% to 100% B with a 1.1 minute wash at 100% B (A=0.1% formic acid/5% acetonitrile/94.9% water, B=0.1% formic acid/5% water/94.9% acetonitrile); MS (ES) M+H expect=298.0, found=298.3.

Workup

  1. temperaturewas refluxed for 1.5 h
  2. washThe resultant solution was then washed with 100 mL of sat. sodium bicarbonate aqueous solution, brine solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified by silica gel chromatography (20% EtOAc in hexane to 35% EtOAc in hexane)

Sources & evidence

ORD record
ord-98a127827337404ca6e89af3156b2d29
Source dataset
uspto-grants-2010_08
Patent number
US07777035B2

Reaction notes

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