1-Hydroxybenzotriazole → 2,6-difluoro-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-nitrobenzamide

HRID 1943941Notes

Reaction equation

HRID 1943941 reaction equation
[CH3:1][O:2][C:3]1[C:11]2[C:6](=[N:7][CH:8]=[C:9]([NH2:12])[CH:10]=2)[NH:5][N:4]=1.[F:13][C:14]1[C:22]([N+:23]([O-:25])=[O:24])=[CH:21][CH:20]=[C:19]([F:26])[C:15]=1[C:16](O)=[O:17].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O.C(OCC)(=O)C>[F:13][C:14]1[C:22]([N+:23]([O-:25])=[O:24])=[CH:21][CH:20]=[C:19]([F:26])[C:15]=1[C:16]([NH:12][C:9]1[CH:10]=[C:11]2[C:3]([O:2][CH3:1])=[N:4][NH:5][C:6]2=[N:7][CH:8]=1)=[O:17]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 3026292,6-Difluoro-3-nitrobenzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 442236943-Methoxy-1H-pyrazolo[3,4-B]pyridin-5-amine

Product 1

HCID 670890542,6-difluoro-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-nitrobenzamideYield 68.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Methoxy-1H-pyrazolo[3,4-b]pyridin-5-amine (563 mg, 3.43 mmol) in N,N-dimethylformamide (17.1 mL) was sequentially treated with 2,6-difluoro-3-nitrobenzoic acid (766.2 mg, 3.772 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (723.2 mg, 3.772 mmol), and 1-hydroxybenzotriazole (509.7 mg, 3.772 mmol) at ambient temperature. After 24 hours, the reaction mixture was diluted with ethyl acetate, washed with water (4×), sodium bicarbonate (2×), and brine (1×), dried over sodium sulfate, and concentrated. The crude product was triturated with dichloromethane to provide 2,6-difluoro-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-nitrobenzamide (820.6 mg, 2.350 mmol, 68.5% yield) as a solid. MS (APCI-neg) m/z=347.8 (M−H).

Workup

  1. washwashed with water (4×), sodium bicarbonate (2×), and brine (1×)
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. customThe crude product was triturated with dichloromethane

Sources & evidence

ORD record
ord-044e9a6f2b824eefbfbd379f2266280e
Source dataset
uspto-grants-2013_03
Patent number
US08394795B2

Reaction notes

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