Dimethylformamide → HCID 86692435, compound

HRID 1748467Notes

Reaction equation

HRID 1748467 reaction equation
[CH:1]1(B(O)O)[CH2:3][CH2:2]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN(C)C=O.[CH2:20]([O:22][C:23]([C:25]1[CH:26]=[N:27][N:28]([C:31]2[C:36]([Cl:37])=[CH:35][C:34](Br)=[CH:33][N:32]=2)[C:29]=1[CH3:30])=[O:24])[CH3:21]>O>[CH2:20]([O:22][C:23]([C:25]1[CH:26]=[N:27][N:28]([C:31]2[C:36]([Cl:37])=[CH:35][C:34]([CH:1]3[CH2:3][CH2:2]3)=[CH:33][N:32]=2)[C:29]=1[CH3:30])=[O:24])[CH3:21]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 86692432HCID 86692432, compound

Product 1

HCID 86692435HCID 86692435, compoundYield 26.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Cyclopropylboronic acid (269 mg), tripotassium phosphate (1.61 g) and 1,1′-bis(diphenylphosphino)ferrocene-palladium (II) dichloride dichloromethane complex (124 mg) were added to a N,N-dimethylformamide solution (15 ml) of 1-(5-bromo-3-chloropyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (1.03 g) described in Reference Example 44(2), and the mixture was stirred at 100° C. for six hours. The reaction solution was cooled to room temperature, diluted with water, filtered through Celite and the filtrate was extracted with ethyl acetate three times. The organic layer was washed with water and saturated brine, 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-cyclopropylpyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (240 mg) as a pale yellow solid.

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. filtrationfiltered through Celite
  3. extractionthe filtrate was extracted with ethyl acetate three times
  4. washThe organic layer was washed with water and saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customThe resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-95bf4f2fe80e45ee8f09045064335d2a
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

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