Potassium Phosphate, Tribasic → N-(4-(2,4-difluorophenoxy)-3-(6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenyl)ethanesulfonamide

HRID 632746Notes

Reaction equation

HRID 632746 reaction equation
[CH3:1][N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[C:5]2[CH:17]=[CH:18][N:19]([S:20]([C:23]3[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:4]=2[C:3]1=[O:30].Br[C:32]1[CH:33]=[C:34]([NH:47][S:48]([CH2:51][CH3:52])(=[O:50])=[O:49])[CH:35]=[CH:36][C:37]=1[O:38][C:39]1[CH:44]=[CH:43][C:42]([F:45])=[CH:41][C:40]=1[F:46].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].CC12CC3(C)P(C4C=CC=CC=4)C(C)(CC(C)(O3)O1)O2>[F:46][C:40]1[CH:41]=[C:42]([F:45])[CH:43]=[CH:44][C:39]=1[O:38][C:37]1[CH:32]=[CH:33][C:34]([NH:47][S:48]([CH2:51][CH3:52])(=[O:49])=[O:50])=[CH:35][C:36]=1[C:6]1[C:5]2[CH:17]=[CH:18][N:19]([S:20]([C:23]3[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:4]=2[C:3](=[O:30])[N:2]([CH3:1])[CH:7]=1

Participants

6

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 117770988N-(3-bromo-4-(2,4-difluorophenoxy)phenyl)ethanesulfonamide

Product 1

HCID 117773894N-(4-(2,4-difluorophenoxy)-3-(6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenyl)ethanesulfonamideYield 93.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 534277901,3,5,7-Tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantaneCatalyst

Conditions

Temperature
60 °C

Procedure

A mixture of 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 (6.00 g, 14.0 mmol), N-(3-bromo-4-(2,4-difluorophenoxy)phenyl)ethanesulfonamide (5.77 g, 14.7 mmol), 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantane (0.205 g, 0.700 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.321 g, 0.350 mmol) and potassium phosphate (2.97 g, 14.0 mmol) was combined and sparged with argon for 30 minutes. A mixture of dioxane (60 mL) and water (15 mL) was sparged with nitrogen for 30 minutes and transferred by syringe into the reaction vessel under argon. The reaction mixture was stirred at 60° C. for 2 hours, cooled to ambient temperature, and partitioned between ethyl acetate and water. The organic layer was washed with brine, dried (anhydrous sodium sulfate), treated with silica gel (2-4 g) for 45 minutes, filtered and concentrated to afford N-(4-(2,4-difluorophenoxy)-3-(6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenyl)ethanesulfonamide (8 g, 13.04 mmol, 93% yield).

Workup

  1. customsparged with argon for 30 minutes
  2. additionA mixture of dioxane (60 mL) and water (15 mL)
  3. customwas sparged with nitrogen for 30 minutes
  4. customtransferred by syringe into the reaction vessel under argon
  5. temperaturecooled to ambient temperature
  6. custompartitioned between ethyl acetate and water
  7. washThe organic layer was washed with brine
  8. dry with materialdried (anhydrous sodium sulfate)
  9. additiontreated with silica gel (2-4 g) for 45 minutes
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-99fabf65b0754003af0efabd2db932f5
Source dataset
uspto-grants-2016_04
Patent number
US09321765B2

Reaction notes

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