2-Bromopyridine → (3-(Methylsulfinyl)-1-(5-(pyridin-2-yl)pyrimidin-2-yl)-1H-indol-6-yl)(morpholino)methanone

HRID 630463Notes

Reaction equation

HRID 630463 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[O:18])[CH:15]=3)[C:10]([S:25]([CH3:27])=[O:26])=[CH:9]2)=[N:6][CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][N:53]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.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>[CH3:27][S:25]([C:10]1[C:11]2[C:16](=[CH:15][C:14]([C:17]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[O:18])=[CH:13][CH:12]=2)[N:8]([C:5]2[N:4]=[CH:3][C:2]([C:52]3[CH:57]=[CH:56][CH:55]=[CH:54][N:53]=3)=[CH:7][N:6]=2)[CH:9]=1)=[O:26]

Participants

8

Reactant 5

HCID 79732-BromopyridineHCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 118666026(1-(5-Bromopyrimidin-2-yl)-3-(methylsulfinyl)-1H-indol-6-yl)(morpholino)methanone

Product 1

HCID 118666344(3-(Methylsulfinyl)-1-(5-(pyridin-2-yl)pyrimidin-2-yl)-1H-indol-6-yl)(morpholino)methanone

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
115 °C

Procedure

[1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex (0.014 g, 0.016 mmol) was added under an argon atmosphere at room temperature to a solution of [(1-(5-bromopyrimidin-2-yl)-3-(methylsulfinyl)-1H-indol-6-yl)(morpholino)methanone (0.15 g, 0.33 mmol), bis(pinacolato)diboron (0.093 g, 0.37 mmol) and potassium acetate (0.099 g, 0.99 mmol) in dioxane (6 mL). The reaction mixture was heated at 115° C. for 40 min and then cooled to ambient temperature. For the Suzuki coupling, which was also carried out under an inert atmosphere, 2-bromopyridine (0.078 g, 0.49 mmol), tetrakis(triphenylphosphine)palladium(0) (0.019 g, 0.016 mmol) and 2M potassium carbonate solution (0.5 mL) were added. The mixture was stirred at 100° C. for 2.5 h and then filtered through a plug of celite. The filtrate was concentrated and the resulting residue purified by flash column chromatography [methanol/dichloromethane=1:50] and a subsequent trituration with dichloromethane/hexane (1:2). White solid. Yield: 45 mg (30% of theory)

Workup

  1. temperaturecooled to ambient temperature
  2. additionwere added
  3. filtrationfiltered through a plug of celite
  4. concentrationThe filtrate was concentrated
  5. customthe resulting residue purified by flash column chromatography [methanol/dichloromethane=1:50]

Sources & evidence

ORD record
ord-9286f1c9bc714c9d949745543436cbda
Source dataset
uspto-grants-2016_04
Patent number
US09315490B2

Reaction notes

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