Potassium Carbonate → (3-amino-2,6-difluoro-phenyl)-[5-(2-methyl-pyrimidin-5-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]methanone

HRID 60116Notes

Reaction equation

HRID 60116 reaction equation
[NH2:1][C:2]1[C:3]([F:29])=[C:4]([C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17](B4OC(C)(C)C(C)(C)O4)[CH:18]=3)[NH:13][CH:12]=2)=[O:10])[C:5]([F:8])=[CH:6][CH:7]=1.Br[C:31]1[CH:32]=[N:33][C:34]([CH3:37])=[N:35][CH:36]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.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]>[NH2:1][C:2]1[C:3]([F:29])=[C:4]([C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:31]4[CH:32]=[N:33][C:34]([CH3:37])=[N:35][CH:36]=4)[CH:18]=3)[NH:13][CH:12]=2)=[O:10])[C:5]([F:8])=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 143877445-Bromo-2-methylpyrimidineHCID 58368802HCID 58368802, compound

Product 1

HCID 58368924(3-amino-2,6-difluoro-phenyl)-[5-(2-methyl-pyrimidin-5-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]methanone

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

In a reaction vial, (3-amino-2,6-difluoro-phenyl)-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-methanone is combined with (48, 0.850 g, 2.129 mmol), 5-bromo-2-methyl-pyrimidine (49, 0.737 g, 4.26 mmol), potassium carbonate (0.589 g, 4.26 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.174 g, 0.213 mmol) in 14.20 mL of dioxane and 7.10 mL of water (7.10 mL). The reaction is heated at 100° C. overnight. Upon cooling, the reaction mixture is partitioned between water/brine and ethyl acetate/tetrahydrofuran and then filtered through Celite. The organic layer is separated and concentrated under vacuum. The resulting residue is purified by silica gel column chromatography eluting with 0-10% methanol in dichloromethane to provide the desired compound as a tan solid (50, ˜220 mg).

Workup

  1. customIn a reaction vial
  2. temperatureUpon cooling
  3. customthe reaction mixture is partitioned between water/brine and ethyl acetate/tetrahydrofuran
  4. filtrationfiltered through Celite
  5. customThe organic layer is separated
  6. concentrationconcentrated under vacuum
  7. customThe resulting residue is purified by silica gel column chromatography
  8. washeluting with 0-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-5416b2e15b9c42a5b1e871eb8154979b
Source dataset
uspto-grants-2016_09
Patent number
US09440969B2

Reaction notes

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