Dimethylformamide → 6-fluoro-7-iodo-1H-pyrazolo[4,3-b]pyridine

HRID 1522562Notes

Reaction equation

HRID 1522562 reaction equation
[F:1][C:2]1[C:3]([I:12])=[C:4]2[NH:10][N:9]=[C:8](N)[C:5]2=[N:6][CH:7]=1.CN(C=O)C.N(OC(C)(C)C)=O.I>O>[F:1][C:2]1[C:3]([I:12])=[C:4]2[NH:10][N:9]=[CH:8][C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10906Tert-Butyl nitriteHCID 24841Hydrogen iodideHCID 674704486-fluoro-7-iodo-1H-pyrazolo[4,3-b]pyridin-3-amine

Product 1

HCID 674703846-fluoro-7-iodo-1H-pyrazolo[4,3-b]pyridineYield 11.68%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

6-Fluoro-7-iodo-1H-pyrazolo[4,3-b]pyridin-3-amine (2.0 g, 7.19 mmol) was combined with DMF (15 mL) and cooled to 0° C. before tert-butyl nitrite (1.709 mL, 14.39 mmol) was added. The reaction mixture was then warmed to room temperature and heated at 85° C. for 4 hours. The reaction mixture was cooled to room temperature and HI solution (1.614 g, 7.19 mmol) in water (57%) was added and heated to 85° C. for another 8 hours. The mixture was cooled, concentrated, to give a residue which was purified by preparative HPLC using a Sunfire Prep 5 μm C18, 75×30 mm column eluting with a gradient of 25-45% acetonitrile (containing 10 mM NH4HCO3) in water (containing 10 mM NH4HCO3) to give the title compound. (221 mg, 0.840 mmol, 11.68% yield). MS [M+H] found 264.0.

Workup

  1. additionwas added
  2. temperatureheated at 85° C. for 4 hours
  3. temperatureThe reaction mixture was cooled to room temperature
  4. temperatureheated to 85° C. for another 8 hours
  5. temperatureThe mixture was cooled
  6. concentrationconcentrated
  7. customto give a residue which
  8. customwas purified by preparative HPLC
  9. washeluting with a gradient of 25-45% acetonitrile (containing 10 mM NH4HCO3) in water (containing 10 mM NH4HCO3)

Sources & evidence

ORD record
ord-7f2cf70674d547eabd70bd2a26fadc67
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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