Potassium Phosphate, Tribasic → HCID 86692411, compound

HRID 1748442Notes

Reaction equation

HRID 1748442 reaction equation
C(B1O[C:9]([CH3:11])([CH3:10])[C:6]([CH3:8])([CH3:7])O1)(C)=C.C([O:15][C:16]([C:18]1[CH:19]=[N:20][N:21]([C:24]2[CH:29]=CC(Br)=C[N:25]=2)[C:22]=1[CH3:23])=[O:17])C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.O1CCCC1>[CH:9]([C:6]1[CH:7]=[CH:29][C:24]([N:21]2[C:22]([CH3:23])=[C:18]([C:16]([OH:17])=[O:15])[CH:19]=[N:20]2)=[N:25][CH:8]=1)([CH3:10])[CH3:11]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 109974264,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolaneHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 46739344Ethyl 1-(5-bromopyridin-2-yl)-5-methylpyrazole-4-carboxylate

Product 1

HCID 86692411HCID 86692411, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

Isopropenylboronic acid pinacol ester (5.2 ml) was added to 1-(5-bromopyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (6.2 g) described in Reference Example 24(2), palladium (II) acetate (448 mg), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (S-Phos) (820 mg), tripotassium phosphate (0.6 g) and tetrahydrofuran (20 ml), and the mixture was stirred at 100° C. for 8 hours. Water was added and the reaction mixture was extracted with ethyl acetate and the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated in vacuo. To the resultant yellow oil was added 1,4-Dioxane (25 ml) and 10% palladium-carbon (containing ca. 50% of water; 500 mg), and the mixture was stirred under hydrogen atmosphere at room temperature for 5 hours. The reaction solution was filtered through Celite, the filtrate was concentrated in vacuo and the residue was purified with silica gel column chromatography (n-hexane/ethyl acetate). 4N Aqueous solution of sodium hydroxide (5 ml), water (5 ml) and ethanol (10 ml) were added to the resulting oily residue and stirred at 80° C. for 4 hours. The reaction solution was concentrated in vacuo, 1N hydrochloric acid aqueous solution was added to the resulting residue at 0° C., and the precipitated solid was washed with water to give the titled compound (1.56 g) as a pale red solid.

Workup

  1. extractionthe reaction mixture was extracted with ethyl acetate
  2. washthe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. additionTo the resultant yellow oil was added 1,4-Dioxane (25 ml) and 10% palladium-carbon (containing ca. 50% of water; 500 mg)
  6. stirringthe mixture was stirred under hydrogen atmosphere at room temperature for 5 hours
  7. filtrationThe reaction solution was filtered through Celite
  8. concentrationthe filtrate was concentrated in vacuo
  9. customthe residue was purified with silica gel column chromatography (n-hexane/ethyl acetate)
  10. addition4N Aqueous solution of sodium hydroxide (5 ml), water (5 ml) and ethanol (10 ml) were added to the resulting oily residue
  11. stirringstirred at 80° C. for 4 hours
  12. concentrationThe reaction solution was concentrated in vacuo, 1N hydrochloric acid aqueous solution
  13. additionwas added to the resulting residue at 0° C.
  14. washthe precipitated solid was washed with water

Sources & evidence

ORD record
ord-fd1517fa4a724fc48e7f24367a159840
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

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