Potassium Phosphate, Tribasic → 2-[4-chloro-3-(4-fluorophenyl)-5-phenyl-pyrazolo[3,4-c]pyridazin-1-yl]-1-[(3R)-3-fluoropyrrolidin-1-yl]ethanone

HRID 1615709Notes

Reaction equation

HRID 1615709 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[N:6][N:5]=[C:4]2[N:14]([CH2:18][C:19]([N:21]3[CH2:25][CH2:24][C@@H:23]([F:26])[CH2:22]3)=[O:20])[N:15]=[C:16](I)[C:3]=12.[F:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O>[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[N:6][N:5]=[C:4]2[N:14]([CH2:18][C:19]([N:21]3[CH2:25][CH2:24][C@@H:23]([F:26])[CH2:22]3)=[O:20])[N:15]=[C:16]([C:31]3[CH:32]=[CH:33][C:28]([F:27])=[CH:29][CH:30]=3)[C:3]=12

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2856454-Fluorophenylboronic acidHCID 867172722-(4-chloro-3-iodo-5-phenyl-pyrazolo[3,4-c]pyridazin-1-yl)-1-[(3R)-3-fluoropyrrolidin-1-yl]ethanone

Product 1

HCID 737760312-[4-chloro-3-(4-fluorophenyl)-5-phenyl-pyrazolo[3,4-c]pyridazin-1-yl]-1-[(3R)-3-fluoropyrrolidin-1-yl]ethanoneYield 30.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Nitrogen was bubbled through a suspension of 2-(4-chloro-3-iodo-5-phenyl-pyrazolo[3,4-c]pyridazin-1-yl)-1-[(3R)-3-fluoropyrrolidin-1-yl]ethanone (70 mg, 0.144 mmol), 4-fluorophenylboronic acid (22 mg, 0.158 mmol) and K3PO4 (92 mg, 0.43 mmol) in DMF (1.1 mL) and water (0.4 mL) for 20 min. 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (12 mg, 0.014 mmol) was added and the tube sealed and heated using microwave irradiation to 60° C. for 30 min. The crude reaction mixture was filtered and partially purified by preparative HPLC. The residue was purified by chromatography (silica gel, isohexane/ethyl acetate 1:0 to 7:3) to provide Compound 1 (20 mg).

Workup

  1. addition1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (12 mg, 0.014 mmol) was added
  2. customthe tube sealed
  3. temperatureheated
  4. custommicrowave irradiation to 60° C. for 30 min
  5. customThe crude reaction mixture
  6. filtrationwas filtered
  7. custompartially purified by preparative HPLC
  8. customThe residue was purified by chromatography (silica gel, isohexane/ethyl acetate 1:0 to 7:3)

Sources & evidence

ORD record
ord-e7742172d73848a69b1970576ea55626
Source dataset
uspto-grants-2014_07
Patent number
US08765762B2

Reaction notes

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