Dichloromethane → HCID 86656201, compound

HRID 1020935Notes

Reaction equation

HRID 1020935 reaction equation
[CH:1]([O:4]C1C=CC=NC=1)([CH3:3])[CH3:2].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].C(Cl)Cl.C(=O)([O-])[O-].[K+].[K+].Br[C:44]1[C:52]2[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=2)[NH:46][N:45]=1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].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.O.C(O)C.C1(C)C=CC=CC=1.CS(C)=O>[CH:1]([O:4][C:44]1[C:52]2[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=2)[NH:46][N:45]=1)([CH3:3])[CH3:2]

Participants

14

Reactant 6

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 113555083-IsopropyloxypyridineHCID 178419483HCID 178419483, compound

Product 1

HCID 86656201HCID 86656201, compound

Reagents, catalysts & solvents 7

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

5-isopropoxypyridine 2BIa (10 g, 0.046 mol), bis(pinacolato)diboron (14.1 g, 0.056 mol), potassium acetate (13.6 g, 0.14 mol) and PdCl2(dppf)2.CH2Cl2 (3.78 g, 0.0046 mol) were weight into a 2-necked 1 L flask equipped with a water condenser. DMSO (100 ml) was added and the mixture was purged with nitrogen for 15 min. The mixture was heated at 100° C. under nitrogen for 2 hr. After being cooled to r.t., water (100 ml), toluene (100 ml), ethanol (100 ml), potassium carbonate (32 g, 0.23 mol) and bromoindazole 3BI (22.4 g, 0.046 mol) were added. The mixture were purged with nitrogen for 10 min at r.t. and Pd(Ph3P)4 (5.35 g, 0.0046 mol) was added. The final mixture were heated at 100° C. for 2 hr and cooled to r.t. Water and ethyl acetate were added. Solids were filtered through Celite. Layers were separated and the separated organic layer was washed with water (×2). The combined aqueous layers were back extracted with ethyl acetate (×1). The combined organic layers were dried (MgSO4), filtered and solvents were removed in vacuum. Column purification [Hexanes-ethyl acetate=9:1 (v/v)] gave isopropoxyindazole 4BI (20 g, 80%) as yellow solid.

Workup

  1. customequipped with a water condenser
  2. customthe mixture was purged with nitrogen for 15 min
  3. temperatureAfter being cooled to r.t.
  4. customThe mixture were purged with nitrogen for 10 min at r.t.
  5. temperaturecooled to r.t
  6. filtrationSolids were filtered through Celite
  7. customLayers were separated
  8. washthe separated organic layer was washed with water (×2)
  9. extractionThe combined aqueous layers were back extracted with ethyl acetate (×1)
  10. dry with materialThe combined organic layers were dried (MgSO4)
  11. filtrationfiltered
  12. customsolvents were removed in vacuum
  13. customColumn purification [Hexanes-ethyl acetate=9:1 (v/v)]

Sources & evidence

ORD record
ord-81c0fda141484f068ec15f01b50b5557
Source dataset
uspto-grants-2014_05
Patent number
US08716483B2

Reaction notes

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