Dimethylformamide → Methyl 3-cyano-1H-indazole-5-carboxylate

HRID 2404276Notes

Reaction equation

HRID 2404276 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[C:11]#[N:12].[C:13]([O-:16])(=[O:15])C.[Na+].[CH3:18]N(C)C=O>CO.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Pd](Cl)Cl>[C:11]([C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([C:13]([O:16][CH3:18])=[O:15])[CH:3]=2)[NH:7][N:6]=1)#[N:12]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 517045Sodium AcetateHCID 247289115-bromo-1H-indazole-3-carbonitrile

Product 1

HCID 44632177Methyl 3-cyano-1H-indazole-5-carboxylateYield 68%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 887MethanolSolvent

Procedure

A suspension of 5-bromo-3-cyanoindazole (3 g, 13.51 mmol), palladium dichloride 1,1′-bis(diphenylphosphino)ferrocene (1.76 g, 2.16 mmol), sodium acetate (3.32 g, 40.5 mmol), dimethylformamide (1 mL) in methanol (100 mL) was degassed, and kept under carbon monoxide (80 psi) pressure at 80° C. in a autoclave for 16 hours. The mixture was diluted with water (50 mL), filtered through Celite® bed and the filtrate was concentrated. The obtained residue was acidified with 10% citric acid solution and extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous sodium sulfate and concentrated. The obtained crude product was purified by column chromatography (100-200 mesh silica gel) using 10% ethyl acetate in chloroform as eluent to afford methyl 3-cyano-1H-indazole-5-carboxylate (1.8 g, 68%) as a solid. 1HNMR (CDCl3) δ ppm 10.8 (s, 1H), 8.7 (s, 1H), 8.22 (d, 1H), 7.64 (d, 1H), 4.0 (s, 3H).

Workup

  1. customwas degassed
  2. customat 80° C.
  3. customfor 16 hours
  4. additionThe mixture was diluted with water (50 mL)
  5. filtrationfiltered through Celite® bed
  6. concentrationthe filtrate was concentrated
  7. extractionextracted with ethyl acetate (2×100 mL)
  8. washThe combined organic layers were washed with brine (50 mL)
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated
  11. customThe obtained crude product
  12. customwas purified by column chromatography (100-200 mesh silica gel)

Sources & evidence

ORD record
ord-1ca8783634c0488fa6b9c91c975e6201
Source dataset
uspto-grants-2014_08
Patent number
US08802690B2

Reaction notes

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