Water → HCID 86686387, compound

HRID 1043956Notes

Reaction equation

HRID 1043956 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].O.Br[C:9]1[C:14]([F:15])=[CH:13][C:12]([C:16]2[N:20]([CH:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[N:19]=[CH:18][C:17]=2[C:27]([O:29][CH2:30][CH3:31])=[O:28])=[C:11]([F:32])[CH:10]=1.[CH3:33][O:34][C:35]1[C:40](B(O)O)=[C:39]([CH3:44])[CH:38]=[C:37]([CH3:45])[N:36]=1>[Cl-].[Na+].O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C.O1CCOCC1>[F:32][C:11]1[CH:10]=[C:9]([C:40]2[C:35]([O:34][CH3:33])=[N:36][C:37]([CH3:45])=[CH:38][C:39]=2[CH3:44])[C:14]([F:15])=[CH:13][C:12]=1[C:16]1[N:20]([CH:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[N:19]=[CH:18][C:17]=1[C:27]([O:29][CH2:30][CH3:31])=[O:28]

Participants

9

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 86686388HCID 86686388, compoundHCID 86686389HCID 86686389, compound

Product 1

HCID 86686387HCID 86686387, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
110 °C

Procedure

Pd(PPh3)4 (50 mg), cesium carbonate (282 mg) and water (0.5 mL) were added to a mixed solution of ethyl 5-(4-bromo-2,5-difluorophenyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylate obtained in Preparation Example 10 (180 mg), (2-methoxy-4,6-dimethylpyridin-3-yl)boronic acid obtained in Preparation Example 27 (90 mg) and 1,4-dioxane (2 mL), and the mixture was stirred at 110° C. for six hours. After cooling the reaction mixture to room temperature, ethyl acetate and brine were added, and the mixture was filtered through a cotton plug. The organic layer was separated and dried over anhydrous magnesium sulfate. The desiccant was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (ethyl acetate/n-heptane, 25% to 46% to 53%) to give the title compound (157 mg).

Workup

  1. temperatureAfter cooling the reaction mixture to room temperature
  2. filtrationthe mixture was filtered through a cotton plug
  3. customThe organic layer was separated
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe desiccant was removed by filtration
  6. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-080f957879cf4629a592e89b726a3e75
Source dataset
uspto-grants-2013_10
Patent number
US08563565B2

Reaction notes

Loading…