Toluene → HCID 117769915, compound

HRID 1526351Notes

Reaction equation

HRID 1526351 reaction equation
[NH2:1][C:2]1[C:6]2[C:7](=[O:27])[N:8]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[Cl:26])[CH:9]=[C:10](B3OC(C)(C)C(C)(C)O3)[C:5]=2[NH:4][N:3]=1.Cl[C:29]1[N:34]=[CH:33][CH:32]=[CH:31][N:30]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(C)C=CC=CC=1>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.C(O)C>[NH2:1][C:2]1[C:6]2[C:7](=[O:27])[N:8]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[Cl:26])[CH:9]=[C:10]([C:29]3[N:34]=[CH:33][CH:32]=[CH:31][N:30]=3)[C:5]=2[NH:4][N:3]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 62657Potassium Phosphate, TribasicHCID 744042-ChloropyrimidineHCID 131733168HCID 131733168, compound

Product 1

HCID 117769915HCID 117769915, compoundYield 19.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
120 °C

Procedure

A mixture of 3-amino-7-bromo-5-(2-chlorophenyl)-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one obtained in Step B of Example 18 (200 mg), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-1,3,2-dioxaborolane (179 mg), (1,1′-bis(diphenylphosphino)ferrocene)dichloropalladium(II) (21.6 mg), potassium acetate (116 mg) and N,N-dimethylformamide (3.0 mL) was stirred overnight at 110° C. under argon atmosphere. 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 to give 3-amino-5-(2-chlorophenyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one (277 mg). A mixture of 3-amino-5-(2-chlorophenyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one (277 mg), 2-chloropyrimidine (131 mg), tripotassium phosphate (365 mg), tetrakis(triphenylphosphine)palladium(0) (99.0 mg), toluene (5.0 mL), ethanol (1.0 mL) and water (1.0 mL) was stirred overnight at 120° C. under argon atmosphere. 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 silica gel chromatography (basic silica gel, methanol/ethyl acetate) to give the title compound (47.0 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 chromatography (basic silica gel, methanol/ethyl acetate)

Sources & evidence

ORD record
ord-4992848d22d34ca4bf212767393ac096
Source dataset
uspto-grants-2015_07
Patent number
US09085578B2

Reaction notes

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