Thiophenol → 1-(1-Methylethyl)-N-[6-(1H-pyrazolo[3,4-b]pyridin-4-yl)-1H-indazol-4-yl]-1H-pyrazole-5-carboxamide

HRID 244718Notes

Reaction equation

HRID 244718 reaction equation
I[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8](S(C3C=CC=CC=3)(=O)=O)[N:9]=[CH:10][C:3]=12.C[N:21]1[CH:25]=[C:24](C)[C:23]([C:27]([NH:29][C:30]2[CH:38]=[C:37]([Sn](C)(C)C)[CH:36]=[C:35]3[C:31]=2[CH:32]=[N:33][N:34]3S(C2C=CC=CC=2)(=O)=O)=[O:28])=[N:22]1.[C:52]1(S)[CH:57]=CC=C[CH:53]=1>CN(C=O)C>[CH3:53][CH:52]([N:22]1[C:23]([C:27]([NH:29][C:30]2[CH:38]=[C:37]([C:2]3[CH:7]=[CH:6][N:5]=[C:4]4[NH:8][N:9]=[CH:10][C:3]=34)[CH:36]=[C:35]3[C:31]=2[CH:32]=[N:33][NH:34]3)=[O:28])=[CH:24][CH:25]=[N:21]1)[CH3:57]

Participants

5

Reactant 3

HCID 7969ThiophenolHCID 583564471,4-Dimethyl-N-[1-(phenylsulfonyl)-6-(trimethylstannanyl)-1H-indazol-4-yl]-1H-pyrazole-3-carboxamideHCID 673189474-Iodo-1-(phenylsulfonyl)-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 583563451-(1-Methylethyl)-N-[6-(1H-pyrazolo[3,4-b]pyridin-4-yl)-1H-indazol-4-yl]-1H-pyrazole-5-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
135 °C

Procedure

4-Iodo-1-(phenylsulfonyl)-1H-pyrazolo[3,4-b]pyridine (69 mg) in DMF (0.4 ml) was added to 1,4-dimethyl-N-[1-(phenylsulfonyl)-6-(trimethylstannanyl)-1H-indazol-4-yl]-1H-pyrazole-3-carboxamide (100 mg) in DMF (0.4 ml). Solvias catalyst (4 mg) was added and the sealed vessel was heated in the Anton Paar microwave at 135° C. for 20 min. PS-thiophenol resin was added and the reaction was stirred overnight before being filtered onto a C18SPE cartridge, pre-washed with 0.1% TFA, with acetonitrile. The cartridge was washed with 0.1% TFA in acetonitrile and the collected solvent was removed under a stream of nitrogen. The residue was dissolved in DMSO (1 ml) and purified by MDAP (method C). The solvent was evaporated in vacuo. The residue was dissolved in isopropanol (0.3 ml), 2M sodium hydroxide (aq) (0.3 ml) was added and the reaction was left at room temperature overnight. The solvent was removed under a stream of nitrogen and the residue was dissolved in DMSO (0.5 ml) and purified by MDAP (method C). The solvent was evaporated in vacuo to give title compound, 9 mg.

Workup

  1. filtrationbefore being filtered onto a C18SPE cartridge
  2. washpre-washed with 0.1% TFA, with acetonitrile
  3. washThe cartridge was washed with 0.1% TFA in acetonitrile
  4. customthe collected solvent was removed under a stream of nitrogen
  5. dissolutionThe residue was dissolved in DMSO (1 ml)
  6. custompurified by MDAP (method C)
  7. customThe solvent was evaporated in vacuo
  8. dissolutionThe residue was dissolved in isopropanol (0.3 ml)
  9. addition2M sodium hydroxide (aq) (0.3 ml) was added
  10. waitthe reaction was left at room temperature overnight
  11. customThe solvent was removed under a stream of nitrogen
  12. dissolutionthe residue was dissolved in DMSO (0.5 ml)
  13. custompurified by MDAP (method C)
  14. customThe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-424c5cf71c5f41c3948d6ef67aa0d923
Source dataset
uspto-grants-2014_02
Patent number
US08658635B2

Reaction notes

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