Hydrochloric Acid → Methyl[3-methyl-5-(pyridin-2-yl)-1-(pyrimidin-5-yl)-1h-pyrazol-4-yl]acetate

HRID 2068487Notes

Reaction equation

HRID 2068487 reaction equation
N1C=CC=CC=1.[CH3:7][O:8][C:9](=[O:23])[CH2:10][C:11]1[C:12]([CH3:22])=[N:13][NH:14][C:15]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1.[N:24]1[CH:29]=[C:28](B(O)O)[CH:27]=[N:26][CH:25]=1.Cl.S(=O)(=O)(O)O>ClCCl.CO.C([O-])(=O)C.[Cu+2].C([O-])(=O)C.O>[CH3:7][O:8][C:9](=[O:23])[CH2:10][C:11]1[C:12]([CH3:22])=[N:13][N:14]([C:28]2[CH:29]=[N:24][CH:25]=[N:26][CH:27]=2)[C:15]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 1118Sulfuric AcidHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 178499524HCID 178499524, compound

Product 1

HCID 131730045Methyl[3-methyl-5-(pyridin-2-yl)-1-(pyrimidin-5-yl)-1h-pyrazol-4-yl]acetate

Reagents, catalysts & solvents 4

HCID 8895Cupric acetateCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

1.767 g (9.73 mmol) of copper(II) acetate and 1.049 ml (12.973 mmol) of pyridine were added to 1.5 g (6.486 mmol) of methyl[3-methyl-5-(pyridin-2-yl)-1H-pyrazol-4-yl]acetate in 20 ml of dichloromethane. 1.607 g (12.973 mmol) of 5-pyrimidinylboronic acid were then added, and the mixture was stirred at 20° C. for 48 h. The mixture was poured into 1-molar aqueous HCl (10 ml) and extracted with dichloromethane. The combined organic phases were dried with magnesium sulfate, filtrered and concentrated. The crude product was purified by preparative HPLC. This gave a mixture of ester and acid which was heated at reflux in methanol with a drop of sulfuric acid for 4 h. The reaction mixture was poured into water (20 ml), neutralized and extracted with dichloromethane. The combined organic phases were dried with magnesium sulfate and concentrated. This gave 0.031 g of product (1.47% of theory).

Workup

  1. extractionextracted with dichloromethane
  2. dry with materialThe combined organic phases were dried with magnesium sulfate
  3. concentrationconcentrated
  4. customThe crude product was purified by preparative HPLC
  5. customThis gave
  6. temperaturewas heated
  7. extractionextracted with dichloromethane
  8. dry with materialThe combined organic phases were dried with magnesium sulfate
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-7636fbc066c54e8ba753a61d3df79527
Source dataset
uspto-grants-2012_10
Patent number
US08298994B2

Reaction notes

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