Sodium Carbonate → 6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-amine

HRID 244696Notes

Reaction equation

HRID 244696 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH2:20])[C:5]2[CH:6]=[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:29]2[CH:37]=[CH:36][CH:35]=[C:34]3[C:30]=2[CH:31]=[CH:32][NH:33]3)O1.C(=O)([O-])[O-].[Na+].[Na+]>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]>[NH:33]1[C:34]2[C:30](=[C:29]([C:2]3[CH:3]=[C:4]([NH2:20])[C:5]4[CH:6]=[N:7][N:8]([S:11]([C:14]5[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=5)(=[O:13])=[O:12])[C:9]=4[CH:10]=3)[CH:37]=[CH:36][CH:35]=2)[CH:31]=[CH:32]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 113224711H-Indole-4-boronic acid, pinacol esterHCID 582558116-Bromo-1-(phenylsulfonyl)-1H-indazol-4-amine

Product 1

HCID 582680186-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-amine

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

6-Bromo-1-(phenylsulfonyl)-1H-indazol-4-amine (3 g, 8.52 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (2.278 g, 9.37 mmol), Pd(dppf)Cl2 (0.623 g, 0.852 mmol) and sodium carbonate (2.71 g, 25.6 mmol) were divided between 2× microwave vials and dissolved in 1,4-dioxane (16 mL) and water (16 mL); 8 ml of each solvent in each vial. The vials were heated in the microwave at 100° C. for 10 min. The mixtures were combined and filtered through Celite, washing with EtOAc. The resulting mixture was partitioned between water (100 ml) and EtOAc (100 ml) and the layers separated. The aqueous layer was extracted with further EtOAc (2×50 ml) and the organic extracts were combined, passed through a hydrophobic frit and the solvent removed in vacuo to give a brown solid which was pre-adsorbed onto silica and added to the top of a 100 g silica SPE cartridge. This was eluted with 0-100% EtOAc/cyclohexane over 60 minutes on the FlashMaster II. The product-containing fractions were combined and the solvent was removed in vacuo to afford the title compound as orange crystals which were dried on a high vacuum line for 1 hour.

Workup

  1. filtrationfiltered through Celite
  2. washwashing with EtOAc
  3. customThe resulting mixture was partitioned between water (100 ml) and EtOAc (100 ml)
  4. customthe layers separated
  5. extractionThe aqueous layer was extracted with further EtOAc (2×50 ml)
  6. customthe solvent removed in vacuo
  7. customto give a brown solid which
  8. additionadded to the top of a 100 g silica SPE cartridge
  9. washThis was eluted with 0-100% EtOAc/cyclohexane over 60 minutes on the FlashMaster II
  10. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-487d1d56110847318a5a79c4ef7e655a
Source dataset
uspto-grants-2014_02
Patent number
US08658635B2

Reaction notes

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