Sodium Carbonate → 4-[4'-(Ethylsulfonyl)-2',6-difluorobiphenyl-3-yl]-7-(propan-2-yl)-7H-imidazol[4,5-c]pyridazine

HRID 1845990Notes

Reaction equation

HRID 1845990 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](B3OC(C)(C)C(C)(C)O3)[CH:13]=2)=[C:8]([F:28])[CH:7]=1)(=[O:5])=[O:4])[CH3:2].Cl[C:30]1[C:31]2[N:38]=[CH:37][N:36]([CH:39]([CH3:41])[CH3:40])[C:32]=2[N:33]=[N:34][CH:35]=1.C([O-])([O-])=O.[Na+].[Na+]>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:30]3[C:31]4[N:38]=[CH:37][N:36]([CH:39]([CH3:41])[CH3:40])[C:32]=4[N:33]=[N:34][CH:35]=3)[CH:13]=2)=[C:8]([F:28])[CH:7]=1)(=[O:5])=[O:4])[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 867232144-chloro-7-isopropyl-7H-imidazo[4,5-c]pyridazineHCID 902176162-(4'-(Ethylsulfonyl)-2',6-difluoro-[1,1'-biphenyl]-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 762872624-[4'-(Ethylsulfonyl)-2',6-difluorobiphenyl-3-yl]-7-(propan-2-yl)-7H-imidazol[4,5-c]pyridazineYield 80%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 2-[4′-(ethylsulfonyl)-2′,6-difluorobiphenyl-3-yl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Preparation 47, 48 mg, 0.12 mmol) and 4-chloro-7-isopropyl-7H-imidazo[4,5-c]pyridazine (Preparation 6, 22 mg, 0.11 mmol) in anhydrous dioxane (0.56 mL) was added aqueous Na2CO3 solution (2M, 0.17 mL, 0.34 mmol) and a stream of nitrogen gas was bubbled through the suspension for 5 minutes. Tetrakistriphenylphosphine palladium(0) (2.3 mg, 0.002 mmol) was added and the mixture was heated under microwave irradiation at 120° C. for a total of 15 minutes. The reaction mixture was cooled, diluted with water (20 mL) and extracted with EtOAc (3×15 mL). The organic layers were combined, washed with brine, dried over Na2SO4, filtered and the filtrate was evaporated in vacuo to leave a tan sticky solid that was purified by silica gel column chromatography eluting with heptane:EtOAc to afford the title compound as a tan solid in 80% yield, 40 mg.

Workup

  1. customa stream of nitrogen gas was bubbled through the suspension for 5 minutes
  2. temperatureThe reaction mixture was cooled
  3. extractionextracted with EtOAc (3×15 mL)
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customthe filtrate was evaporated in vacuo
  8. customto leave a tan sticky solid
  9. customthat was purified by silica gel column chromatography
  10. washeluting with heptane

Sources & evidence

ORD record
ord-203b9a313ebe4b518ac57f18844128f1
Source dataset
uspto-grants-2015_02
Patent number
US08952008B2

Reaction notes

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