Dimethylformamide → HCID 86692437, compound

HRID 1748469Notes

Reaction equation

HRID 1748469 reaction equation
CB(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH3:13]N(C)C=O.[CH2:18]([O:20][C:21]([C:23]1[CH:24]=[N:25][N:26]([C:29]2[C:34]([Cl:35])=[CH:33][C:32](Br)=[CH:31][N:30]=2)[C:27]=1[CH3:28])=[O:22])[CH3:19]>O>[CH2:18]([O:20][C:21]([C:23]1[CH:24]=[N:25][N:26]([C:29]2[C:34]([Cl:35])=[CH:33][C:32]([CH3:13])=[CH:31][N:30]=2)[C:27]=1[CH3:28])=[O:22])[CH3:19]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 62657Potassium Phosphate, TribasicHCID 139377Methylboronic Acid3×HCID 86692432HCID 86692432, compound

Product 1

HCID 86692437HCID 86692437, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Methylboronic acid (457 mg), tripotassium phosphate (3.40 g) and 1,1′-bis(diphenylphosphino)ferrocene-palladium (II) dichloride dichloromethane complex (296 mg) were added to a N,N-dimethylformamide solution (36 ml) of 1-(5-bromo-3-chloropyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (2.50 g) described in Reference Example 44(2), and the mixture was stirred at 100° C. for three hours. Methylboronic acid (154 mg) and 1,1′-bis(diphenylphosphino)ferrocene-palladium (II) dichloride dichloromethane complex (103 mg) were subsequently added and the mixture was further stirred for three hours. The reaction solution was cooled to room temperature and left stand for 16 hours, and methylboronic acid (153 mg) and 1,1′-bis(diphenylphosphino)ferrocene-palladium (II) dichloride dichloromethane complex (114 mg) were further added and the mixture was stirred again at 100° C. for five hours. After completion of the reaction, the reaction solution was cooled to room temperature, diluted with water and extracted with ethyl acetate three times. The organic layer was washed with water, dried over anhydrous sodium sulfate and concentrated. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate) to give 1-(3-chloro-5-methylpyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (1.03 g).

Workup

  1. stirringthe mixture was further stirred for three hours
  2. temperatureThe reaction solution was cooled to room temperature
  3. waitleft stand for 16 hours
  4. stirringthe mixture was stirred again at 100° C. for five hours
  5. customAfter completion of the reaction
  6. temperaturethe reaction solution was cooled to room temperature
  7. extractionextracted with ethyl acetate three times
  8. washThe organic layer was washed with water
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated
  11. customThe resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-acc3adafac754ceca0883a5d7cb40bc3
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

Loading…