HCID 52917575, compound → HCID 51346965, compound

HRID 2172984Notes

Reaction equation

HRID 2172984 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[C:9]([C:11]2([NH:14][C:15]([C:17]3[C:18]4[CH:19]=[N:20][N:21]([C:27]5[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=5)[C:22]=4[CH:23]=[C:24](Br)[CH:25]=3)=[O:16])[CH2:13][CH2:12]2)[CH:8]=[CH:7][N:6]=1)(=[O:4])=[O:3].CS([C:38]1C=C(C2(NC(C3C4C=NN(C5C=CC(F)=CC=5)C=4C=C(I)C=3)=O)CC2)C=C[N:39]=1)(=O)=O>CN(C=O)C.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.[C-]#N.[Zn+2].[C-]#N>[CH3:1][S:2]([C:5]1[CH:10]=[C:9]([C:11]2([NH:14][C:15]([C:17]3[C:18]4[CH:19]=[N:20][N:21]([C:27]5[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=5)[C:22]=4[CH:23]=[C:24]([C:38]#[N:39])[CH:25]=3)=[O:16])[CH2:13][CH2:12]2)[CH:8]=[CH:7][N:6]=1)(=[O:4])=[O:3]

Participants

6

Reactant 2

HCID 52917575HCID 52917575, compoundHCID 52917576HCID 52917576, compound

Product 1

HCID 51346965HCID 51346965, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a stirred solution of 6-bromo-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid [1-(2-methanesulfonyl-pyridin-4-yl)-cyclopropyl]-amide, and 1-(4-fluoro-phenyl)-6-iodo-1H-indazole-4-carboxylic acid [1-(2-methanesulfonyl-pyridin-4-yl)-cyclopropyl]-amide (150 mg) in DMF (1.0 mL, degassed and anhydrous) is added tetrakis(triphenylphosphine)palladium (33 mg, 0.028 mmol) and zinc cyanide (40 mg, 0.34 mmol). The solution is evacuated and purged with Argon (3 times) and warmed to 120° C. After 3 hours, the reaction is cooled to room temperature, diluted with saturated aqueous ammonium chloride (50 mL), and extracted with ethyl acetate (3×50 mL). The combined organic layers are washed with brine (50 mL), dried over magnesium sulfate, filtered and concentrated. The residue is purified on SiO2 using a gradient of 50-100% ethyl acetate in heptane to give a solid, which is triturated with ethyl ether to afford the title product.

Workup

  1. customThe solution is evacuated
  2. custompurged with Argon (3 times)
  3. temperaturethe reaction is cooled to room temperature
  4. additiondiluted with saturated aqueous ammonium chloride (50 mL)
  5. extractionextracted with ethyl acetate (3×50 mL)
  6. washThe combined organic layers are washed with brine (50 mL)
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue is purified on SiO2 using a gradient of 50-100% ethyl acetate in heptane
  11. customto give a solid, which
  12. customis triturated with ethyl ether

Sources & evidence

ORD record
ord-ffca95e857d54f7a949f8bfae093c265
Source dataset
uspto-grants-2015_06
Patent number
US09056858B2

Reaction notes

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