Potassium Phosphate, Tribasic → 6-fluoro-1-(phenylsulfonyl)-3-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)-1H-indole

HRID 2274762Notes

Reaction equation

HRID 2274762 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][C:7]([F:11])=[CH:8][CH:9]=2)[N:4]([S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)(=[O:14])=[O:13])[CH:3]=1.CC1(C)C(C)(C)OB([C:29]2[CH:30]=[N:31][N:32]([C:34]3[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=3)[CH:33]=2)O1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([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]>[F:11][C:7]1[CH:6]=[C:5]2[C:10]([C:2]([C:29]3[CH:30]=[N:31][N:32]([C:34]4[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=4)[CH:33]=3)=[CH:3][N:4]2[S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)(=[O:14])=[O:13])=[CH:9][CH:8]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 665212834-(4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)pyridine2×HCID 863462493-Bromo-6-fluoro-1-(phenylsulfonyl)-1H-indole2×

Product 1

HCID 1180602116-fluoro-1-(phenylsulfonyl)-3-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)-1H-indoleYield 96.4%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of 3-bromo-6-fluoro-1-(phenylsulfonyl)-1H-indole (Intermediate 2; 317 mg; 0.9 mmol) and 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)pyridine (Intermediate 9; 485 mg; 1.80 mmol), Pd2 dba3 (48 mg; 0.05 mmol) and X-phos (96 mg; 0.20 mmol), and K3PO4 (954 mg; 4.5 mmol) in 1,4-dioxane (8 mL) and water (1 mL) was flushed with argonand reacted at 125° C. for 25 minutes in a microwave reactor. The reaction mixture was filtered through Celite, washed with EtOAc (50 mL), concentrated, and purified by a silica gel chromatography (petroleum ether/EtOAc=1/1) to afford 363 mg (96%) of the title compound as a yellow solid.

Workup

  1. customwas flushed with argonand
  2. customreacted at 125° C. for 25 minutes in a microwave reactor
  3. filtrationThe reaction mixture was filtered through Celite
  4. washwashed with EtOAc (50 mL)
  5. concentrationconcentrated
  6. custompurified by a silica gel chromatography (petroleum ether/EtOAc=1/1)

Sources & evidence

ORD record
ord-f8a8d61c57a94176aecef5c1426e7d13
Source dataset
uspto-grants-2015_09
Patent number
US09126984B2

Reaction notes

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