Potassium Phosphate, Tribasic → HCID 89657311, compound

HRID 632742Notes

Reaction equation

HRID 632742 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17])[NH2:5].[CH3:18][N:19]1[CH:24]=[C:23](B2OC(C)(C)C(C)(C)O2)[C:22]2[CH:34]=[CH:35][N:36]([S:37]([C:40]3[CH:46]=[CH:45][C:43]([CH3:44])=[CH:42][CH:41]=3)(=[O:39])=[O:38])[C:21]=2[C:20]1=[O:47].CC12CC3(C)P(C4C=CC=CC=4)C(C)(CC(C)(O3)O1)O2.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.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]>[NH2:5][C:4]1[CH:6]=[CH:7][C:8]([O:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[F:17])=[C:2]([C:23]2[C:22]3[CH:34]=[CH:35][N:36]([S:37]([C:40]4[CH:46]=[CH:45][C:43]([CH3:44])=[CH:42][CH:41]=4)(=[O:39])=[O:38])[C:21]=3[C:20](=[O:47])[N:19]([CH3:18])[CH:24]=2)[CH:3]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 534277901,3,5,7-Tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantaneHCID 61720969HCID 61720969, compoundHCID 867210626-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one

Product 1

HCID 89657311HCID 89657311, compoundYield 72.3%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 3-bromo-4-(2,4-difluorophenoxy)aniline (5.0 g, 11.67 mmol), 6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (3.85 g, 12.84 mmol), 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantane (0.399 g, 1.366 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.321 g, 0.350 mmol), and potassium phosphate (6.19 g, 29.2 mmol) in dioxane (50 mL) and water (12.5 mL) was degassed and back-filled with nitrogen several times. The reaction mixture was heated at 60° C. for 16 hours and then cooled to ambient temperature. The reaction mixture was partitioned between water and ethyl acetate. The aqueous layer was extracted with additional ethyl acetate three times. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, 60% ethyl acetate/hexanes) to provide 4-(5-amino-2-(2,4-difluorophenoxy)phenyl)-6-methyl-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (4.40 g, 72.3% yield).

Workup

  1. customwas degassed
  2. additionback-filled with nitrogen several times
  3. temperaturecooled to ambient temperature
  4. customThe reaction mixture was partitioned between water and ethyl acetate
  5. extractionThe aqueous layer was extracted with additional ethyl acetate three times
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash column chromatography (silica gel, 60% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-032ec910c4794172910ea9b145040db9
Source dataset
uspto-grants-2016_04
Patent number
US09321765B2

Reaction notes

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