Sodium Bicarbonate → HCID 178434584, compound

HRID 2359051Notes

Reaction equation

HRID 2359051 reaction equation
C(=O)([O-])O.[Na+].Br[C:7]1[N:11](CC2C=CC(OC)=CC=2)[N:10]=[C:9]([C:21]2[S:22][C:23]([Cl:26])=[CH:24][CH:25]=2)[C:8]=1[C:27]1[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=1.Br[C:34]1C(C2C=CN=CC=2)=C(C2SC(Cl)=CC=2)N(CC2C=CC(OC)=CC=2)N=1.CB1OB(C)OB(C)O1>C(COC)OC.O.C(OCC)(=O)C>[Cl:26][C:23]1[S:22][C:21]([C:9]2[NH:10][N:11]=[C:7]([CH3:34])[C:8]=2[C:27]2[CH:28]=[CH:29][N:30]=[CH:31][CH:32]=2)=[CH:25][CH:24]=1

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 574072TrimethylboroxineHCID 67260634HCID 67260634, compoundHCID 67261945HCID 67261945, compound

Product 1

HCID 178434584HCID 178434584, compoundYield 30%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of sodium hydrogen carbonate (2.0 mmol) and PdCl2dppf:CH2Cl2 1:1 (0.03 mmol) under argon, was added a degassed solution of 4-[5-bromo-3-(5-chloro-2-thienyl)-1-(4-methoxybenzyl)-1H-pyrazol-4-yl]pyridine and 4-[3-bromo-5-(5-chloro-2-thienyl)-1-(4-methoxybenzyl)-1H-pyrazol-4-yl]pyridine (mixture of isomers 2:1, 0.65 mmol) in 10.5 mL dimethoxyethane and 3 mL of water. Trimethylboroxin (50% solution in THF, 1.3 mmol) was then added and the mixture was stirred at 90° C. for 3 h. After cooling to room temperature, water and ethyl acetate were added. The aqueous layer was extracted with ethyl acetate and the combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated. The residue was dissolved in 3 mL of trifluoroacetic acid and stirred at 65° C. for 2 h. Water and ethyl acetate were added. And the aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with a saturated solution of sodium hydrogen carbonate, dried over MgSO4, filtered and concentrated. The residue was purified by chromatography on silica gel (dichloromethane/methanol 20:1 to 10:1) to afford 57 mg of 4-[5-(5-chloro-2-thienyl)-3-methyl-1H-pyrazol-4-yl]pyridine (30% yield).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washthe combined organic extracts were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in 3 mL of trifluoroacetic acid
  8. stirringstirred at 65° C. for 2 h
  9. additionWater and ethyl acetate were added
  10. extractionAnd the aqueous layer was extracted with ethyl acetate
  11. washThe combined organic extracts were washed with a saturated solution of sodium hydrogen carbonate
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe residue was purified by chromatography on silica gel (dichloromethane/methanol 20:1 to 10:1)

Sources & evidence

ORD record
ord-3f4cf197b9b3492aaf793e0230da57dd
Source dataset
uspto-grants-2014_04
Patent number
US08685974B2

Reaction notes

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