Triphenylphosphine → 6-{2-[2-amino-5-(4-fluoro-2H-pyrazol-3-yl)pyridin-3-yl]-1H-benzimidazol-5-yl}-5-methyl-4,5-dihydro-2H-pyridazin-3-one

HRID 241404Notes

Reaction equation

HRID 241404 reaction equation
[NH2:1][C:2]1[C:7]([C:8]2[NH:12][C:11]3[CH:13]=[CH:14][C:15]([C:17]4[CH:18]([CH3:24])[CH2:19][C:20](=[O:23])[NH:21][N:22]=4)=[CH:16][C:10]=3[N:9]=2)=[CH:6][C:5](I)=[CH:4][N:3]=1.[F:26][C:27]1[CH:28]=[N:29][NH:30][C:31]=1[Sn](CCCC)(CCCC)CCCC.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl-].[Li+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[Cu](I)I>[NH2:1][C:2]1[C:7]([C:8]2[NH:12][C:11]3[CH:13]=[CH:14][C:15]([C:17]4[CH:18]([CH3:24])[CH2:19][C:20](=[O:23])[NH:21][N:22]=4)=[CH:16][C:10]=3[N:9]=2)=[CH:6][C:5]([C:28]2[NH:29][N:30]=[CH:31][C:27]=2[F:26])=[CH:4][N:3]=1

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 433294Lithium ChlorideHCID 111530444-fluoro-5-(tributylstannyl)-1H-pyrazoleHCID 178429558HCID 178429558, compound

Product 1

HCID 1784295576-{2-[2-amino-5-(4-fluoro-2H-pyrazol-3-yl)pyridin-3-yl]-1H-benzimidazol-5-yl}-5-methyl-4,5-dihydro-2H-pyridazin-3-one

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

100 mg (0.224 mmol) of 6-[2-(2-amino-5-iodopyridin-3-yl)-1H-benzimidazol-5-yl]-5-methyl-4,5-dihydro-2H-pyridazin-3-one, 252.2 mg (0.672 mmol) of 4-fluoro-5-tributylstannanyl-1H-pyrazole, 41.5 mg (0.045 mmol) of tris(dibenzylideneacetone)dipalladium(0), 23.5 mg (0.090 mmol) of triphenylphosphine, 28.5 mg (0.672 mmol) of lithium chloride and 8.5 mg (0.045 mmol) of copper iodide in 2 ml of dioxane are introduced into a nitrogen-filled reaction vessel. The mixture is stirred at 100° C. for 14 h under a nitrogen protective atmosphere. The reaction mixture is cooled to room temperature, and the solvent is removed. DCM and 2N HCl are added to the residue. The precipitate is separated off and washed with DCM/water. The precipitate is purified further via preparative RP-HPLC, giving 6-{2-[2-amino-5-(4-fluoro-2H-pyrazol-3-yl)pyridin-3-yl]-1H-benzimidazol-5-yl}-5-methyl-4,5-dihydro-2H-pyridazin-3-one; HPLC-MS [M+H]+ 405.2;

Workup

  1. additionfilled
  2. customreaction vessel
  3. temperatureThe reaction mixture is cooled to room temperature
  4. customthe solvent is removed
  5. additionDCM and 2N HCl are added to the residue
  6. customThe precipitate is separated off
  7. washwashed with DCM/water
  8. customThe precipitate is purified further via preparative RP-HPLC

Sources & evidence

ORD record
ord-165aed75c2534050981ef4772016255b
Source dataset
uspto-grants-2014_02
Patent number
US08648201B2

Reaction notes

Loading…