Cesium carbonate → 5-(Benzyloxy)-6-(6-methylpyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1661999Notes

Reaction equation

HRID 1661999 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][C:17]=1Br)[N:14]([CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)[N:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.CC([O-])=O.[K+].Br[C:49]1[CH:50]=[CH:51][C:52]([CH3:55])=[N:53][CH:54]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.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.[Fe+2].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.CCOC(C)=O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][C:17]=1[C:49]1[CH:54]=[N:53][C:52]([CH3:55])=[CH:51][CH:50]=1)[N:14]([CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)[N:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

11

Reactant 5

HCID 10796Cesium carbonateHCID 517044Potassium AcetateHCID 12010205-Bromo-2-methylpyridineHCID 2733548Bis(pinacolato)diboraneHCID 667670665-(Benzyloxy)-6-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

Product 1

HCID 667671245-(Benzyloxy)-6-(6-methylpyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleYield 46.2%

Reagents, catalysts & solvents 5

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 5-(benzyloxy)-6-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (4 g, 10.3 mmol) in 1,4-dioxane (25 mL) is added bis(pinacolato)diboron (3 g, 11.8 mmol), dppf (0.3 g, 541 μmol), PdCl2(dppf) (0.42 g, 514 μmol) and KOAc (2 g, 20.4 mmol) under N2. After the reaction mixture is stirred at reflux for 5 hours, 5-bromo-2-methylpyridine (2.1 g, 12.2 mmol), tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) (0.6 g, 519 μmol) and Cs2CO3 (4 g, 12.3 mmol) are added and the mixture is stirred at reflux overnight. The reaction mixture is cooled and filtered, the filtrate is concentrated. The residue is purified by silica gel column chromatography eluting with PE:EtOAc (2:1) to give the product (1.9 g, 46.0% yield). MS (m/z): 400.1 (M+H).

Workup

  1. temperatureat reflux for 5 hours
  2. stirringthe mixture is stirred
  3. temperatureat reflux overnight
  4. temperatureThe reaction mixture is cooled
  5. filtrationfiltered
  6. concentrationthe filtrate is concentrated
  7. customThe residue is purified by silica gel column chromatography
  8. washeluting with PE

Sources & evidence

ORD record
ord-3b136d0de8584be19934fae2556c9d03
Source dataset
uspto-grants-2011_10
Patent number
US08030302B2

Reaction notes

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