Dimethylformamide → HCID 117770754, compound

HRID 1526317Notes

Reaction equation

HRID 1526317 reaction equation
[NH2:1][C:2]1[C:6]2[C:7](=[O:17])[N:8]([CH:12]([CH:14]([CH3:16])[CH3:15])[CH3:13])[CH:9]=[C:10](Br)[C:5]=2[NH:4][N:3]=1.[CH3:18][N:19]1[CH:23]=[CH:22][C:21](B2OC(C)(C)C(C)(C)O2)=[N:20]1.C(=O)([O-])[O-].[Na+].[Na+].CN(C)C=O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[NH2:1][C:2]1[C:6]2[C:7](=[O:17])[N:8]([CH:12]([CH:14]([CH3:16])[CH3:15])[CH3:13])[CH:9]=[C:10]([C:21]3[CH:22]=[CH:23][N:19]([CH3:18])[N:20]=3)[C:5]=2[NH:4][N:3]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 27600771-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 117770577HCID 117770577, compound

Product 1

HCID 117770754HCID 117770754, compoundYield 10.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3-amino-7-bromo-5-(3-methylbutan-2-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one obtained in Step G (332 mg), 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (347 mg), tetrakis(triphenylphosphine)palladium(0) (128 mg), aqueous sodium carbonate solution (2 M, 1.11 ml) and N,N-dimethylformamide (6.0 mL) was heated with microwave irradiation at 120° C. for 1 hr. The reaction mixture was cooled to room temperature, and poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (methanol/ethyl acetate), and then HPLC (C18, mobile phase: water/acetonitrile (containing 0.1% TFA)). To the obtained fraction was added saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give the title compound (36.0 mg).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with water and saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (methanol/ethyl acetate)
  7. additionTo the obtained fraction was added saturated aqueous sodium hydrogen carbonate solution
  8. extractionthe mixture was extracted with ethyl acetate
  9. dry with materialThe extract was dried over anhydrous magnesium sulfate
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-8181d236e7ca4af0987eeb52326e4c69
Source dataset
uspto-grants-2015_07
Patent number
US09085578B2

Reaction notes

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