Potassium Phosphate, Tribasic → HCID 86721079, compound

HRID 930938Notes

Reaction equation

HRID 930938 reaction equation
Br[C:2]1[C:3]([O:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=2[F:21])=[N:4][CH:5]=[C:6]([CH2:8][S:9]([CH3:12])(=[O:11])=[O:10])[CH:7]=1.[CH3:22][N:23]1[CH:28]=[C:27](B2OC(C)(C)C(C)(C)O2)[C:26]2[CH:38]=[CH:39][N:40]([S:41]([C:44]3[CH:50]=[CH:49][C:47]([CH3:48])=[CH:46][CH:45]=3)(=[O:43])=[O:42])[C:25]=2[C:24]1=[O:51].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:21][C:15]1[CH:16]=[C:17]([F:20])[CH:18]=[CH:19][C:14]=1[O:13][C:3]1[C:2]([C:27]2[C:26]3[CH:38]=[CH:39][N:40]([S:41]([C:44]4[CH:50]=[CH:49][C:47]([CH3:48])=[CH:46][CH:45]=4)(=[O:43])=[O:42])[C:25]=3[C:24](=[O:51])[N:23]([CH3:22])[CH:28]=2)=[CH:7][C:6]([CH2:8][S:9]([CH3:12])(=[O:11])=[O:10])=[CH:5][N:4]=1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 867210626-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-oneHCID 867210783-Bromo-2-(2,4-difluorophenoxy)-5-(methylsulfonylmethyl)pyridine

Product 1

HCID 86721079HCID 86721079, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
60 °C

Procedure

The product from Example 311e (0.075 g, 0.198 mmol), the product from Example 6a (0.085 g, 0.198 mmol), tris(dibenzylideneacetone)dipalladium(0) (5.45 mg, 5.95 μmol), 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamante (5.80 mg, 0.020 mmol) and potassium phosphate (0.126 g, 0.595 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 for 2 hours at 60° C. and partitioned between ethyl acetate and water. The organic layer was washed with saturated aqueous sodium chloride, dried (Na2SO4), treated with 3-mercaptopropyl functionalized silica gel, filtered, and concentrated. Purification by trituration in dichloromethane afforded the title compound (0.083 g, 70%).

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 (Na2SO4)
  7. additiontreated with 3-mercaptopropyl functionalized silica gel
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by trituration in dichloromethane

Sources & evidence

ORD record
ord-7e75cec054b1432590ed511cbc730649
Source dataset
uspto-grants-2016_03
Patent number
US09296741B2

Reaction notes

Loading…