Sodium Carbonate → 7-Ethyl-4-(4'-(ethylsulfonyl)-2'-fluoro-6-methoxy-[1,1'-biphenyl]-3-yl)-7H-imidazo[4,5-c]pyridazine

HRID 1845991Notes

Reaction equation

HRID 1845991 reaction equation
[CH2:1]([S:3]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:17]([O:18][CH3:19])=[CH:16][CH:15]=[C:14](B3OC(C)(C)C(C)(C)O3)[CH:13]=2)=[C:8]([F:29])[CH:7]=1)(=[O:5])=[O:4])[CH3:2].Cl[C:31]1[C:32]2[N:39]=[CH:38][N:37]([CH2:40][CH3:41])[C:33]=2[N:34]=[N:35][CH:36]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:40]([N:37]1[C:33]2[N:34]=[N:35][CH:36]=[C:31]([C:14]3[CH:13]=[C:12]([C:9]4[CH:10]=[CH:11][C:6]([S:3]([CH2:1][CH3:2])(=[O:5])=[O:4])=[CH:7][C:8]=4[F:29])[C:17]([O:18][CH3:19])=[CH:16][CH:15]=3)[C:32]=2[N:39]=[CH:38]1)[CH3:41]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 552967654-chloro-7-ethyl-7H-imidazo(4,5-c)pyridazineHCID 867232202-(4'-(Ethylsulfonyl)-2'-fluoro-6-methoxy-[1,1'-biphenyl]-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 867232197-Ethyl-4-(4'-(ethylsulfonyl)-2'-fluoro-6-methoxy-[1,1'-biphenyl]-3-yl)-7H-imidazo[4,5-c]pyridazineYield 26%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To 2-(4′-(ethylsulfonyl)-2′-fluoro-6-methoxy-[1,1′-biphenyl]-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Preparation 69, 90 mg, 0.21 mmol) in dioxane (2.5 mL) and water (1 mL) was added 4-chloro-7-ethyl-7H-imidazo[4,5-c]pyridazine (Preparation 8, 40 mg, 0.21 mmol) and sodium carbonate (68 mg, 0.64 mmol). The reaction was degassed and tetrakis(triphenylphosphine) palladium(0) (25 mg, 0.02 mmol) was added. The reaction was further degassed and then heated to 110° C. for 2 hours and then cooled to room temperature. The reaction mixture was diluted with EtOAc (40 mL) was passed through celite and the solvent removed in vacuo. The crude material was purified by reverse phase column chromatography eluting with a gradient of 0.1% formic acid in MeCN/water. The resulting residue was dissolved in DMSO (1 mL) and purified using preparative HPLC to give the title compound as a colourless solid in 26% yield, 24 mg.

Workup

  1. customThe reaction was degassed
  2. customThe reaction was further degassed
  3. temperaturecooled to room temperature
  4. additionThe reaction mixture was diluted with EtOAc (40 mL)
  5. customthe solvent removed in vacuo
  6. customThe crude material was purified by reverse phase column chromatography
  7. washeluting with a gradient of 0.1% formic acid in MeCN/water
  8. dissolutionThe resulting residue was dissolved in DMSO (1 mL)
  9. custompurified

Sources & evidence

ORD record
ord-daa71901b4f54da2bee0c04c4dd804cc
Source dataset
uspto-grants-2015_02
Patent number
US08952008B2

Reaction notes

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