1,4-Dimethyl-N-[1-(phenylsulfonyl)-6-(trimethylstannanyl)-1H-indazol-4-yl]-1H-pyrazole-3-carboxamide → N-[6-(6-Cyano-1H-indol-4-yl)-1H-indazol-4-yl]-1,4-dimethyl-1H-pyrazole-3-carboxamide

HRID 520649Notes

Reaction equation

HRID 520649 reaction equation
Br[C:2]1[CH:10]=[C:9]([C:11]#[N:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2S(C1C=CC([N+]([O-])=O)=CC=1)(=O)=O.[CH3:25][N:26]1[CH:30]=[C:29]([CH3:31])[C:28]([C:32]([NH:34][C:35]2[CH:43]=[C:42]([Sn](C)(C)C)[CH:41]=[C:40]3[C:36]=2[CH:37]=[N:38][N:39]3S(C2C=CC=CC=2)(=O)=O)=[O:33])=[N:27]1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C=O)C>[C:11]([C:9]1[CH:8]=[C:7]2[C:3]([CH:4]=[CH:5][NH:6]2)=[C:2]([C:42]2[CH:41]=[C:40]3[C:36]([CH:37]=[N:38][NH:39]3)=[C:35]([NH:34][C:32]([C:28]3[C:29]([CH3:31])=[CH:30][N:26]([CH3:25])[N:27]=3)=[O:33])[CH:43]=2)[CH:10]=1)#[N:12]

Participants

5

Reactant 2

HCID 583564471,4-Dimethyl-N-[1-(phenylsulfonyl)-6-(trimethylstannanyl)-1H-indazol-4-yl]-1H-pyrazole-3-carboxamideHCID 666922724-Bromo-1-[(4-nitrophenyl)sulfonyl]-1H-indole-6-carbonitrile

Product 1

HCID 53233212N-[6-(6-Cyano-1H-indol-4-yl)-1H-indazol-4-yl]-1,4-dimethyl-1H-pyrazole-3-carboxamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

4-Bromo-1-[(4-nitrophenyl)sulfonyl]-1H-indole-6-carbonitrile (70 mg), 1,4-dimethyl-N-[1-(phenylsulfonyl)-6-(trimethylstannanyl)-1H-indazol-4-yl]-1H-pyrazole-3-carboxamide (51 mg) and Pd(PPh3)4 (22 mg) were weighed to a microwave vial and DMF (1 ml) was added. The reaction was heated at 120° C. for 1 h, then cooled and passed through a silica (1 g) cartridge, which had been pre-washed with methanol and washed through with methanol:DCM. The solvent was dried under nitrogen blowdown. The residue was purified using MDAP (method K but using an isocratic 50:50 solvent mix over 10 min). Purified fraction was dissolved in methanol (1 ml) and 2M NaOH (aq) (2 ml) was added and the reaction left at RT over the weekend. The reaction was neutralised using 2M HCl (aq) and dried under nitrogen blowdown. The residue was taken into water and extracted into ethyl acetate. The ethyl acetate was passed through a hydrophobic frit, then through an SAX cartridge pre-conditioned with ethyl acetate. The solvent was evaporated by nitrogen blow down to give title compound, 12 mg.

Workup

  1. additionwas added
  2. temperaturecooled
  3. washhad been pre-washed with methanol
  4. washwashed through with methanol
  5. customThe solvent was dried under nitrogen
  6. customThe residue was purified
  7. additionmix over 10 min)
  8. customPurified fraction
  9. dissolutionwas dissolved in methanol (1 ml)
  10. addition2M NaOH (aq) (2 ml) was added
  11. waitthe reaction left at RT over the weekend
  12. customdried under nitrogen
  13. extractionextracted into ethyl acetate
  14. customThe solvent was evaporated by nitrogen blow down

Sources & evidence

ORD record
ord-ddfb70eb47554b59934a953c87838a19
Source dataset
uspto-grants-2016_05
Patent number
US09326987B2

Reaction notes

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