Potassium Carbonate → HCID 52914483, compound

HRID 341042Notes

Reaction equation

HRID 341042 reaction equation
Br[C:2]1[CH:3]=[C:4]([F:32])[C:5]([CH2:8][N:9]2[C:18]3[C:17]([F:19])=[CH:16][CH:15]=[C:14]([F:20])[C:13]=3[C:12]3=[N:21][N:22]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[F:31])[C:23](=[O:24])[C:11]3=[CH:10]2)=[N:6][CH:7]=1.[CH3:33][N:34]1[CH:38]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH:36]=[N:35]1.C(=O)([O-])[O-].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>CS(C)=O.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:19][C:17]1[C:18]2[N:9]([CH2:8][C:5]3[C:4]([F:32])=[CH:3][C:2]([C:37]4[CH:36]=[N:35][N:34]([CH3:33])[CH:38]=4)=[CH:7][N:6]=3)[CH:10]=[C:11]3[C:23](=[O:24])[N:22]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[F:31])[N:21]=[C:12]3[C:13]=2[C:14]([F:20])=[CH:15][CH:16]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 52914482HCID 52914482, compound

Product 1

HCID 52914483HCID 52914483, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

5-[(5-Bromo-3-fluoropyridin-2-yl)methyl]-6,9-difluoro-2-(2-fluorophenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (Example 103, 63 mg, 0.13 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (45 mg, 0.21 mmol, 1.7 equiv), potassium carbonate (52 mg, 0.38 mmol, 3 equiv), palladium(II) acetate (5.7 mg, 0.025 mmol, 0.2 equiv) and 2-dicyclohexylphosphino-2′,4′,6′-tri-iso-propyl-1,1′-biphenyl (28 mg, 0.058 mmol, 0.46 equiv) were combined in dimethylsulfoxide (0.9 mL) and water (0.2 mL). The mixture was sparged under an atmosphere of nitrogen, the vessel was sealed and placed into a preheated oil bath at 88° C. for 4 hours. The mixture was cooled to ambient temperature, poured into water (25 mL) and extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed once with water (10 mL) and brine (10 mL), dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (eluting with 98:2; chloroform:methanol), providing the titled compound: high resolution mass spectrometry (ES+) m/z 505.1385 [(M+H)+; calculated for C26H17F4N6O: 505.1395].

Workup

  1. customThe mixture was sparged under an atmosphere of nitrogen
  2. customthe vessel was sealed
  3. additionpoured into water (25 mL)
  4. extractionextracted with ethyl acetate (2×50 mL)
  5. washThe combined organic extracts were washed once with water (10 mL) and brine (10 mL)
  6. dry with materialdried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica gel chromatography (eluting with 98:2; chloroform:methanol)

Sources & evidence

ORD record
ord-c43f73d40239434a9e32f3e97c510c19
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

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