Cesium carbonate → Darigabat

HRID 1845984Notes

Reaction equation

HRID 1845984 reaction equation
[CH2:1]([N:3]1[C:7]2[N:8]=[N:9][CH:10]=[C:11]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[C:14](I)[CH:13]=3)[C:6]=2[N:5]=[CH:4]1)[CH3:2].[CH2:20]([S:22]([C:25]1[CH:30]=[CH:29][C:28](B2OC(C)(C)C(C)(C)O2)=[C:27]([O:40][CH3:41])[CH:26]=1)(=[O:24])=[O:23])[CH3:21].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.CCOC(C)=O.[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[CH2:1]([N:3]1[C:7]2[N:8]=[N:9][CH:10]=[C:11]([C:12]3[CH:13]=[C:14]([C:28]4[CH:29]=[CH:30][C:25]([S:22]([CH2:20][CH3:21])(=[O:24])=[O:23])=[CH:26][C:27]=4[O:40][CH3:41])[C:15]([F:18])=[CH:16][CH:17]=3)[C:6]=2[N:5]=[CH:4]1)[CH3:2]

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 867232067-ethyl-4-(4-fluoro-3-iodophenyl)-7H-imidazo[4,5-c]pyridazineHCID 867232082-(4-(Ethylsulfonyl)-2-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 76287260DarigabatYield 13%

Reagents, catalysts & solvents 4

HCID 178454861HCID 178454861, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A stirred solution of 7-ethyl-4-(4-fluoro-3-iodophenyl)-7H-imidazo[4,5-c]pyridazine (Preparation 10, 100 mg, 0.27 mmol), 2-(4-ethylsulfonyl-2-methoxyphenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (Preparation 21, 88 mg, 0.27 mmol) and cesium carbonate (177 mg, 0.54 mmol) in dioxane (5 mL) and water (1 mL) was degassed with argon for 10 minutes followed by the addition of 1,1′-bis(di-tert-butylphosphino) ferrocene palladium dichloride (4.4 mg, 0.005 mmol). The resulting mixture was heated at 100° C. for 16 hours, cooled to room temperature and diluted with EtOAc (15 mL). The organic layer was washed with water (10 mL) and saturated brine solution (10 mL) then dried over Na2SO4, filtered and concentrated in vacuo. Purification by silica gel column chromatography eluting with CH2Cl2:MeOH 98:2 afforded the title compound as off white solid in 13% yield, 15 mg.

Workup

  1. temperaturecooled to room temperature
  2. washThe organic layer was washed with water (10 mL) and saturated brine solution (10 mL)
  3. dry with materialthen dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by silica gel column chromatography
  7. washeluting with CH2Cl2:MeOH 98:2

Sources & evidence

ORD record
ord-20ef1c37707545e0a1eeb22faa8d4006
Source dataset
uspto-grants-2015_02
Patent number
US08952008B2

Reaction notes

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