Potassium Phosphate, Tribasic → 2-(4-cyclopropyl-1H-pyrazol-1-yl)-5-nitropyridine

HRID 537579Notes

Reaction equation

HRID 537579 reaction equation
I[C:2]1[CH:3]=[N:4][N:5]([C:7]2[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[CH:9][N:8]=2)[CH:6]=1.[CH:16]1(B(O)O)[CH2:18][CH2:17]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:16]1([C:2]2[CH:3]=[N:4][N:5]([C:7]3[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[CH:9][N:8]=3)[CH:6]=2)[CH2:18][CH2:17]1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 644297722-(4-iodo-1H-pyrazol-1-yl)-5-nitropyridine

Product 1

HCID 681576882-(4-cyclopropyl-1H-pyrazol-1-yl)-5-nitropyridineYield 28%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

A flask was charged with a mixture of the 2-(4-iodo-1H-pyrazol-1-yl)-5-nitropyridine (0.600 g, 1.90 mmol), cyclopropylboronic acid (652 mg, 7.59 mmol), palladium acetate (43 mg, 0.19 mmol), tricyclohexylphosphine (112 mg, 0.380 mmol), and tripotassium phosphate (1.41 g, 6.64 mmol) and then equipped with a micro reflux condenser and purged with dry nitrogen. Freshly degassed toluene (10 ml) was added followed by degassed water (0.4 ml) and the mixture was heated to reflux for 12 hours. The reaction mixture was cooled to ambient temperature, then diluted with ethyl acetate and water. The aqueous layer was extracted with ethyl acetate (3×) and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified via ISCO MPLC (SiO2, 0-25% ethyl acetate in heptane) to yield the product (0.12 g, 28%) as a solid. 1H NMR (400 MHz, CDCl3): δ 9.24 (d, J=2.7 Hz, 1H), 8.56 (dd, J=9.1, 2.6 Hz, 1H), 8.32 (s, 1H), 8.08 (d, J=9.0 Hz, 1H), 7.62 (s, 1H), 1.79 (tt, J=8.6, 5.1 Hz, 1H), 0.97 (ddd, J=8.2, 6.1, 4.3 Hz, 2H), 0.64 (dt, J=6.3, 4.7 Hz, 2H).

Workup

  1. customequipped with a micro reflux condenser
  2. custompurged with dry nitrogen
  3. additionFreshly degassed toluene (10 ml) was added
  4. customby degassed water (0.4 ml)
  5. temperaturethe mixture was heated
  6. temperatureto reflux for 12 hours
  7. additiondiluted with ethyl acetate and water
  8. extractionThe aqueous layer was extracted with ethyl acetate (3×)
  9. dry with materialthe combined organic extracts were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe crude material was purified via ISCO MPLC (SiO2, 0-25% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-87e09d43c82d4f0a95a0e5909a5600f3
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Reaction notes

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