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Tricyclohexylphosphine → 4-[4'-(Ethylsulfonyl)-6-fluorobiphenyl-3-yl]-7-(propan-2-yl)-7H-imidazo[4,5-c]pyridazine

HRID 1845987
Notes
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Reaction equation

HRID 1845987 reaction equation
[CH2:1]([S:3]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:17]([F:18])=[CH:16][CH:15]=[C:14](B(O)O)[CH:13]=2)=[CH:8][CH:7]=1)(=[O:5])=[O:4])[CH3:2].Cl[C:23]1[C:24]2[N:31]=[CH:30][N:29]([CH:32]([CH3:34])[CH3:33])[C:25]=2[N:26]=[N:27][CH:28]=1.P([O-])([O-])[O-].[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>O1CCOCC1.O>[CH2:1]([S:3]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:17]([F:18])=[CH:16][CH:15]=[C:14]([C:23]3[C:24]4[N:31]=[CH:30][N:29]([CH:32]([CH3:34])[CH3:33])[C:25]=4[N:26]=[N:27][CH:28]=3)[CH:13]=2)=[CH:8][CH:7]=1)(=[O:5])=[O:4])[CH3:2]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 75806TricyclohexylphosphineHCID 9837043phosphorous acid, tripotassium saltHCID 86723213(4'-(Ethylsulfonyl)-6-fluoro-[1,1'-biphenyl]-3-yl)boronic acidHCID 867232144-chloro-7-isopropyl-7H-imidazo[4,5-c]pyridazine

Product 1

HCID 867232124-[4'-(Ethylsulfonyl)-6-fluorobiphenyl-3-yl]-7-(propan-2-yl)-7H-imidazo[4,5-c]pyridazine
Yield 27%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A stirred solution of 4′-ethylsulfonyl-6-fluorobiphenyl-3-yl-boronic acid (Preparation 65, 30 mg, 0.097 mmol), 4-chloro-7-isopropyl-7H-imidazo[4,5-c]pyridazine (Preparation 6, 15 mg, 0.077 mmol) and potassium phosphite (33 mg, 0.154 mmol) in dioxane (3 mL) and water (0.7 mL) was degassed with argon for 10 minutes followed by the addition of tricyclohexylphosphine (1.72 mg, 0.006 mmol) and tris(dibenzylideneacetone)palladium(0) (2.82 mg, 0.003 mmol). The resulting mixture was heated at 100° C. for 16 hours. The reaction mixture was filtered to remove inorganics and the filtrate was concentrated in vacuo to remove the volatiles. Purification of the crude residue by preparative TLC eluting with 2% MeOH in DCM afforded the title compound as off white solid in 27% yield, 9 mg.

Workup

  1. filtrationThe reaction mixture was filtered
  2. customto remove inorganics
  3. concentrationthe filtrate was concentrated in vacuo
  4. customto remove the volatiles
  5. customPurification of the crude residue by preparative TLC
  6. washeluting with 2% MeOH in DCM

Sources & evidence

ORD record
ord-53b8cb4a168b4f01accf7de5ad725fa9
Source dataset
uspto-grants-2015_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08952008B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes