Cesium carbonate → HCID 66763792, compound

HRID 2188979Notes

Reaction equation

HRID 2188979 reaction equation
Br.Br[C:3]1[CH:8]=[CH:7][N:6]=[N:5][CH:4]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:15][O:16][C:17]1[C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][C:20](B(O)O)=[C:19]([CH3:30])[CH:18]=1.O1CCOCC1>C1(C)C=CC=CC=1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[CH3:15][O:16][C:17]1[CH:18]=[C:19]([CH3:30])[C:20]([C:3]2[CH:8]=[CH:7][N:6]=[N:5][CH:4]=2)=[CH:21][C:22]=1[C:23]([O:25][CH3:26])=[O:24]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 534079064-Bromopyridazine hydrobromideHCID 66763599HCID 66763599, compound

Product 1

HCID 66763792HCID 66763792, compound

Reagents, catalysts & solvents 2

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture containing 4-bromopyridazine hydrobromide (0.20 g, 0.83 mmol), cesium carbonate (1.1 g, 3.3 mmol) and 4-methoxy-5-(methoxycarbonyl)-2-methylphenylboronic acid (0.22 g, 1.0 mmol) was charged with dioxane (8.3 mL). Nitrogen gas was purged through the mixture for 15 min with stirring. Stirring was halted and tris(dibenzylideneacetone) dipalladium(0) (0.38 g, 0.04 mmol) was added, followed by ticyclohexylphosphine (0.04 g, 0.13 mmol) in toluene (0.15 mL). Stirring was resumed and the mixture was heated at 80° C. for 105 minutes under nitrogen gas. The reaction was cooled to RT, filtered and concentrated to a residue. The residue was purified on silica gel (5-100% ethyl acetate/hexanes) to afford methyl 2-methoxy-4-methyl-5-(pyridazin-4-yl)benzoate as an off white solid. 1H NMR (400 MHz, CHLOROFORM-d) 9.32-9.14 (m, 2H), 7.75 (s, 1H), 7.46 (dd, J=5.0, 2.3 Hz, 1H), 6.95 (s, 1H), 3.98 (s, 3H), 3.90 (s, 3H), 2.39 (s, 3H). LCMS retention time: 2.805 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 3 micron, C18, 2.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 0.8 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where solvent A was 10% methanol/90% H2O/10 mM TFA and solvent B was 10% H2O/90% methanol/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 259 (MH+).

Workup

  1. customNitrogen gas was purged through the mixture for 15 min
  2. stirringStirring
  3. stirringStirring
  4. temperatureThe reaction was cooled to RT
  5. filtrationfiltered
  6. concentrationconcentrated to a residue
  7. customThe residue was purified on silica gel (5-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-4782cb6c60494567afa682500f99de63
Source dataset
uspto-grants-2012_12
Patent number
US08324212B2

Reaction notes

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