Sodium Carbonate → 5-(7-Ethyl-7H-imidazo[4,5-c]pyridazin-4-yl)-4'-(ethylsulfonyl)-2'-methoxy-[1,1'-biphenyl]-2-ol

HRID 1845995Notes

Reaction equation

HRID 1845995 reaction equation
Cl[C:2]1[C:3]2[N:10]=[CH:9][N:8]([CH2:11][CH3:12])[C:4]=2[N:5]=[N:6][CH:7]=1.[CH2:13]([S:15]([C:18]1[CH:23]=[CH:22][C:21]([C:24]2[C:25]([OH:39])=[CH:26][CH:27]=[C:28](B3OC(C)(C)C(C)(C)O3)[CH:29]=2)=[C:20]([O:40][CH3:41])[CH:19]=1)(=[O:17])=[O:16])[CH3:14].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>[CH2:11]([N:8]1[C:4]2[N:5]=[N:6][CH:7]=[C:2]([C:28]3[CH:29]=[C:24]([C:21]4[CH:22]=[CH:23][C:18]([S:15]([CH2:13][CH3:14])(=[O:16])=[O:17])=[CH:19][C:20]=4[O:40][CH3:41])[C:25]([OH:39])=[CH:26][CH:27]=3)[C:3]=2[N:10]=[CH:9]1)[CH3:12]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 552967654-chloro-7-ethyl-7H-imidazo(4,5-c)pyridazineHCID 867232264'-(Ethylsulfonyl)-2'-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1'-biphenyl]-2-ol

Product 1

HCID 1363484045-(7-Ethyl-7H-imidazo[4,5-c]pyridazin-4-yl)-4'-(ethylsulfonyl)-2'-methoxy-[1,1'-biphenyl]-2-olYield 11%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

To a stirred solution 4-chloro-7-ethyl-7H-imidazo[4,5-c]pyridazine (Preparation 8, 80 mg, 0.44 mmol) and 4′-(ethylsulfonyl)-2′-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-ol (Preparation 89, 167 mg, 0.44 mmol) in dioxane (15 mL) and water (5 mL) was added sodium carbonate (106 mg, 1.0 mmol) and the reaction mixture was degassed before adding tetrakis(triphenylphosphine) palladium(0) (46 mg, 0.04 mmol). The reaction was heated to 100° C. for 18 hours. After this time the reaction was allowed to cool to room temperature, filtered through celite and the filtrate evaporated under reduced pressure. The crude was purified by silica gel column chromatography eluting with CH2Cl2:MeOH from 95:5 to 9:1 and then further purified by preparative HPLC to afford the title compound as colourless solid 11%, 19 mg.

Workup

  1. customthe reaction mixture was degassed
  2. temperatureto cool to room temperature
  3. filtrationfiltered through celite
  4. customthe filtrate evaporated under reduced pressure
  5. customThe crude was purified by silica gel column chromatography
  6. washeluting with CH2Cl2
  7. customMeOH from 95:5 to 9:1 and then further purified by preparative HPLC

Sources & evidence

ORD record
ord-052d258c822146f48ea0e6ec6514b37c
Source dataset
uspto-grants-2015_02
Patent number
US08952008B2

Reaction notes

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