Sodium Carbonate → HCID 71680623, compound

HRID 1526331Notes

Reaction equation

HRID 1526331 reaction equation
[NH2:1][C:2]1[C:6]2[C:7](=[O:20])[N:8]([C:12]3[C:17]([F:18])=[CH:16][CH:15]=[CH:14][C:13]=3[F:19])[CH:9]=[C:10](Br)[C:5]=2[NH:4][N:3]=1.CC1(C)C(C)(C)OB(B2OC(C)(C)C(C)(C)O2)O1.C([O-])(=O)C.[K+].[CH3:44][N:45]1[CH:49]=[CH:48][C:47](I)=[N:46]1.C(=O)([O-])[O-].[Na+].[Na+]>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.CN(C)C=O>[NH2:1][C:2]1[C:6]2[C:7](=[O:20])[N:8]([C:12]3[C:17]([F:18])=[CH:16][CH:15]=[CH:14][C:13]=3[F:19])[CH:9]=[C:10]([C:47]3[CH:48]=[CH:49][N:45]([CH3:44])[N:46]=3)[C:5]=2[NH:4][N:3]=1

Participants

9

Reactant 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 133340573-Iodo-1-methyl-1H-pyrazoleHCID 117770001HCID 117770001, compound

Product 1

HCID 71680623HCID 71680623, compoundYield 40.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 3-amino-7-bromo-5-(2,6-difluorophenyl)-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one obtained in Step G (270 mg), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-1,3,2-dioxaborolane (281 mg), (1,1′-bis(diphenylphosphino)ferrocene)dichloropalladium(II) (29.0 mg), potassium acetate (155 mg) and N,N-dimethylformamide (4.0 mL) was heated with microwave irradiation at 110° C. for 5 hr. The reaction mixture was cooled to room temperature, and 1-methyl-3-iodopyrazole (329 mg), aqueous sodium carbonate solution (2 M, 0.792 mL) and tetrakis(triphenylphosphine)palladium(0) (91.0 mg) were added thereto at room temperature. The reaction mixture was heated with microwave irradiation at 120° C. for 4 hr. The reaction mixture was cooled to room temperature, water was added thereto, 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 thin layer silica gel chromatography (methanol/dichloromethane) to give the title compound (110 mg).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customat room temperature
  3. temperatureThe reaction mixture was heated with microwave irradiation at 120° C. for 4 hr
  4. temperatureThe reaction mixture was cooled to room temperature
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe extract was washed with water and saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by thin layer silica gel chromatography (methanol/dichloromethane)

Sources & evidence

ORD record
ord-f880e07ed969433a9117812dca8c096e
Source dataset
uspto-grants-2015_07
Patent number
US09085578B2

Reaction notes

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