1,4-Dioxane → 3-Fluoro-6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-amine

HRID 520573Notes

Reaction equation

HRID 520573 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH2:21])[C:5]2[C:6]([F:20])=[N:7][N:8]([S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:9]=2[CH:10]=1.CC1(C)C(C)(C)OB([C:30]2[CH:38]=[CH:37][CH:36]=[C:35]3[C:31]=2[CH:32]=[CH:33][NH:34]3)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>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].O>[F:20][C:6]1[C:5]2[C:4]([NH2:21])=[CH:3][C:2]([C:30]3[CH:38]=[CH:37][CH:36]=[C:35]4[C:31]=3[CH:32]=[CH:33][NH:34]4)=[CH:10][C:9]=2[N:8]([S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])[N:7]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 113224711H-Indole-4-boronic acid, pinacol esterHCID 583564216-Bromo-3-fluoro-1-(phenylsulfonyl)-1H-indazol-4-amine

Product 1

HCID 666916863-Fluoro-6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-amine

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

6-Bromo-3-fluoro-1-(phenylsulfonyl)-1H-indazol-4-amine (350 mg), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (230 mg), potassium phosphate (601 mg) and Pd(dppf)Cl2 (69 mg) were placed in a microwave vial with 1,4-dioxane (5 ml) and water (2.5 ml) and the mixture heated at 110° C. for 30 min. After this time the mixture was partitioned between water (200 ml) and DCM (200 ml) and the DCM layer was collected. The aq layer was extracted with DCM (100 ml) and the combined organic layers dried using a hydrophobic frit and the solvent was removed in vacuo. The residue was adsorbed onto silica gel and purified using chromatography on silica gel eluting with 0-100% ethyl acetate in cyclohexane to give the title compound, 350 mg.

Workup

  1. customAfter this time the mixture was partitioned between water (200 ml) and DCM (200 ml)
  2. customthe DCM layer was collected
  3. extractionThe aq layer was extracted with DCM (100 ml)
  4. customthe combined organic layers dried
  5. customthe solvent was removed in vacuo
  6. custompurified

Sources & evidence

ORD record
ord-249f3cc70d804d65999304599ac6b559
Source dataset
uspto-grants-2016_05
Patent number
US09326987B2

Reaction notes

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