Sodium Carbonate → 2'-Fluoro-N-methyl-5'-[7-(propan-2-yl)-7H-imidazo[4,5-c]pyridazin-4-yl]biphenyl-4-sulfonamide

HRID 1845989Notes

Reaction equation

HRID 1845989 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](B2OC(C)(C)C(C)(C)O2)=[CH:4][C:3]=1[C:17]1[CH:22]=[CH:21][C:20]([S:23]([NH:26][CH3:27])(=[O:25])=[O:24])=[CH:19][CH:18]=1.Cl[C:29]1[C:30]2[N:37]=[CH:36][N:35]([CH:38]([CH3:40])[CH3:39])[C:31]=2[N:32]=[N:33][CH:34]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.CCOC(C)=O.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:29]2[C:30]3[N:37]=[CH:36][N:35]([CH:38]([CH3:40])[CH3:39])[C:31]=3[N:32]=[N:33][CH:34]=2)=[CH:4][C:3]=1[C:17]1[CH:18]=[CH:19][C:20]([S:23]([NH:26][CH3:27])(=[O:24])=[O:25])=[CH:21][CH:22]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 867232144-chloro-7-isopropyl-7H-imidazo[4,5-c]pyridazineHCID 867232182'-Fluoro-N-methyl-5'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1'-biphenyl]-4-sulfonamide

Product 1

HCID 867232172'-Fluoro-N-methyl-5'-[7-(propan-2-yl)-7H-imidazo[4,5-c]pyridazin-4-yl]biphenyl-4-sulfonamideYield 82%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 2′-fluoro-N-methyl-5′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)biphenyl-4-sulfonamide (Preparation 44, 112 mg, 0.29 mmol) and 4-chloro-7-isopropyl-7H-imidazo[4,5-c]pyridazine (Preparation 6, 54 mg, 0.27 mmol) in anhydrous dioxane (1.6 mL) was added aqueous Na2CO3 solution (2M, 0.41 mL, 0.81 mmol) and a stream of nitrogen gas was bubbled through the suspension for 5 minutes. Tetrakistriphenylphosphine palladium(0) (5.8 mg, 0.005 mmol) was added and the mixture was heated under microwave irradiation at 120° C. for 12 minutes. The reaction mixture was cooled and diluted with EtOAc (15 mL) and water (30 mL). The organic phase was extracted and the aqueous layer was back-extracted with EtOAc (2×15 mL). The organic layers were combined, washed with brine, dried over Na2SO4, filtered and the filtrate was evaporated in vacuo to leave a tan solid that was suspended in EtOAc (2.5 mL) and stirred at room temperature for 18 hours. The solid was filtered, rinsed with EtOAc (2×1 mL) and further dried to afford the title compound as an off-white solid in 82% yield, 120 mg.

Workup

  1. customa stream of nitrogen gas was bubbled through the suspension for 5 minutes
  2. temperatureThe reaction mixture was cooled
  3. extractionThe organic phase was extracted
  4. extractionthe aqueous layer was back-extracted with EtOAc (2×15 mL)
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customthe filtrate was evaporated in vacuo
  9. customto leave a tan solid
  10. filtrationThe solid was filtered
  11. washrinsed with EtOAc (2×1 mL)
  12. customfurther dried

Sources & evidence

ORD record
ord-2f321bab8a304b5f877af3314ea3ed98
Source dataset
uspto-grants-2015_02
Patent number
US08952008B2

Reaction notes

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