Potassium Phosphate, Tribasic → 3-(2-(2,4-difluorophenoxy)-5-(methylsulfonylmethyl)pyridin-3-yl)-7-methoxy-1-methyl-1H-pyrrolo[2,3-c]pyridine

HRID 633559Notes

Reaction equation

HRID 633559 reaction equation
[CH3:1][O:2][C:3]1[N:4]=[CH:5][CH:6]=[C:7]2[C:11](B3OC(C)(C)C(C)(C)O3)=[CH:10][N:9]([CH3:21])[C:8]=12.Br[C:23]1[C:24]([O:34][C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][C:36]=2[F:42])=[N:25][CH:26]=[C:27]([CH2:29][S:30]([CH3:33])(=[O:32])=[O:31])[CH:28]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:42][C:36]1[CH:37]=[C:38]([F:41])[CH:39]=[CH:40][C:35]=1[O:34][C:24]1[C:23]([C:11]2[C:7]3[C:8](=[C:3]([O:2][CH3:1])[N:4]=[CH:5][CH:6]=3)[N:9]([CH3:21])[CH:10]=2)=[CH:28][C:27]([CH2:29][S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][N:25]=1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 867210783-Bromo-2-(2,4-difluorophenoxy)-5-(methylsulfonylmethyl)pyridineHCID 903879807-methoxy-1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine

Product 1

HCID 904160973-(2-(2,4-difluorophenoxy)-5-(methylsulfonylmethyl)pyridin-3-yl)-7-methoxy-1-methyl-1H-pyrrolo[2,3-c]pyridineYield 102.7%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
60 °C

Procedure

The product from Example 59A (0.061 g, 0.212 mmol), the product from Example 60E (0.08 g, 0.212 mmol), tris(dibenzylideneacetone)dipalladium(0) (5.8 mg, 6.35 μmol), 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamante (6.2 mg, 0.021 mmol) and potassium phosphate (0.157 g, 0.74 mmol) were combined and sparged with argon for 15 minutes. Meanwhile a solution of 4:1 dioxane/water (2 mL) was sparged with nitrogen for 15 minutes and transferred by syringe into the reaction vessel under argon. The mixture was stirred at 60° C. for 2 hours and partitioned between ethyl acetate and water. The organic layer was washed with saturated aqueous sodium chloride, dried (anhydrous Na2SO4), treated with 3-mercaptopropyl functionalized silica gel, filtered, and concentrated to afford the title compound (0.1 g, 100%).

Workup

  1. customsparged with argon for 15 minutes
  2. customMeanwhile a solution of 4:1 dioxane/water (2 mL) was sparged with nitrogen for 15 minutes
  3. customtransferred by syringe into the reaction vessel under argon
  4. custompartitioned between ethyl acetate and water
  5. washThe organic layer was washed with saturated aqueous sodium chloride
  6. dry with materialdried (anhydrous Na2SO4)
  7. additiontreated with 3-mercaptopropyl functionalized silica gel
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-9cb8e2f89b8643aab3a689dcabd1e0b0
Source dataset
uspto-grants-2016_04
Patent number
US09321764B2

Reaction notes

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