Potassium Phosphate, Tribasic → tert-butyl 4-(6-fluoro-1-(phenylsulfonyl)-1H-indol-3-yl)-1H-pyrazole-1-carboxylate

HRID 2274758Notes

Reaction equation

HRID 2274758 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6](I)=[CH:7][N:8]2[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:29]2[CH:30]=[N:31][N:32]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH:33]=2)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:29]3[CH:30]=[N:31][N:32]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH:33]=3)=[CH:7][N:8]2[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 672798376-fluoro-3-iodo-1-(phenylsulfonyl)-1H-indole2×

Product 1

HCID 118060266tert-butyl 4-(6-fluoro-1-(phenylsulfonyl)-1H-indol-3-yl)-1H-pyrazole-1-carboxylateYield 61%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 6-fluoro-3-iodo-1-(phenylsulfonyl)-1H-indole (Intermediate 3; 535 mg; 1.33 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (588 mg; 2.0 mmol), K3PO4 (848 mg; 4.0 mmol) in dioxane (20 mL) and water (2 mL) was added Pd(dppf)Cl2 (110 mg; 0.13 mmol) under nitrogen. The mixture was stirred at 90° C. overnight. The mixture was filtered through Celite, diluted with EtOAc (100 mL) and water (100 mL). The aqueous layer was extracted with EtOAc (50 mL×2). The combined organic layers were washed with brine (100 mL), dried over anhydrous Na2SO4, concentrated, and purified by a silica gel chromatography (petroleum ether/EtOAc=10/1-2/1) to afford 357 mg (61%) of the title compound as a yellow solid.

Workup

  1. filtrationThe mixture was filtered through Celite
  2. additiondiluted with EtOAc (100 mL) and water (100 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (50 mL×2)
  4. washThe combined organic layers were washed with brine (100 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. custompurified by a silica gel chromatography (petroleum ether/EtOAc=10/1-2/1)

Sources & evidence

ORD record
ord-37e6dab2aa0b456fbcc8cd06b2010538
Source dataset
uspto-grants-2015_09
Patent number
US09126984B2

Reaction notes

Loading…