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

HRID 1615991Notes

Reaction equation

HRID 1615991 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-amineYield 27.8%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
110 °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 (2.28 g, 9.37 mmol), Pd(dppf)Cl2 (0.623 g, 0.852 mmol) and sodium carbonate (2.71 g, 25.6 mmol) were divided equally between 2× microwave vials and each dissolved in 1,4-dioxane (8 mL) and water (8 mL). The vials were heated in the microwave at 110° C. for 15 min, then allowed to cool. 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 and the solvent removed in vacuo. The residue (4.6 g) was pre-adsorbed onto silica, which was added to the top of 2×100 g silica SPE cartridges. These were 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 an orange solid (920 mg).

Workup

  1. temperatureto cool
  2. filtrationfiltered through Celite
  3. washwashing with EtOAc
  4. customThe resulting mixture was partitioned between water (100 ml) and EtOAc (100 ml)
  5. customthe layers separated
  6. extractionThe aqueous layer was extracted with further EtOAc (2×50 ml)
  7. customthe solvent removed in vacuo
  8. additionwas added to the top of 2×100 g silica SPE cartridges
  9. washThese were 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-978128aecc954e57af46714155bf1e25
Source dataset
uspto-grants-2014_07
Patent number
US08765743B2

Reaction notes

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