N-methyl-2-pyrrolidone → 1H-Indazole-4-carbonitrile

HRID 250202Notes

Reaction equation

HRID 250202 reaction equation
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.[CH3:11][N:12]1CCCC1=O>[C-]#N.[Zn+2].[C-]#N.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:11]([C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2)#[N:12]

Participants

5

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 223525484-bromo-1H-indazole

Product 1

HCID 247293471H-Indazole-4-carbonitrile

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
85 °C

Procedure

4-Bromoindazole (1.0 g, Judkins et al., WO 9641803) and zinc cyanide (0.6 g) were added to N-methylpyrrolidinone (12.5 ml) and placed under an argon atmosphere. To this mixture was added tetrakis(triphenylphosphine)palladium(0) (0.88 g) and the reaction was heated to 85° C. overnight. The reaction mixture was cooled and partitioned between ethyl acetate and water, the organic layer was washed with brine, dried (MgSO4), and evaporated to dryness. The product was purified by chromatography on silica gel using ethyl acetate-dichloromethane (5:95) as the eluting solvent to afford 0.581 g pure 4-cyanoindazole.

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between ethyl acetate and water
  3. washthe organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated to dryness
  6. customThe product was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-318f09f9124549e0846d263ad5435b19
Source dataset
uspto-grants-2011_01
Patent number
US07863305B2

Reaction notes

Loading…