Dichloromethane → methyl 3-cyano-1H-indazole-6-carboxylate

HRID 880934Notes

Reaction equation

HRID 880934 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([O:13][CH3:14])=O)=[CH:8][CH:9]=2)[NH:4]N=1.Cl[CH2:16]Cl.[OH-:18].[NH4+:19].[Cl-].[NH4+:21]>CC(N(C)C)=O.[Zn].[C-]#N.[Zn+2].[C-]#N.Cl[Pd]Cl.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].[Cu]I>[C:16]([C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([O:13][CH3:14])=[O:18])=[CH:8][CH:9]=2)[NH:4][N:21]=1)#[N:19]

Participants

10

Reactant 4

HCID 6344DichloromethaneHCID 14923Ammonium HydroxideHCID 25517Ammonium ChlorideHCID 178497289HCID 178497289, compound

Product 1

HCID 67491426methyl 3-cyano-1H-indazole-6-carboxylateYield 73%

Reagents, catalysts & solvents 5

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of methyl 3-iodo-1H-indazole-6-carboxylate (3.0 g, 9.9 mmol), zinc dust (400 mg, 6.11 mmol), zinc cyanide (2.0 g, 17.0 mmol), [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II), complex with dichloromethane (1.15 g, 1.41 mmol), and copper (I) iodide (1.90 g, 9.97 mmol) in dimethylacetamide (55 mL) was purged with nitrogen for 15 minutes. The mixture was stirred at 120° C. for 15 hours. The reaction mixture was cooled, diluted with ethyl acetate (250 mL), and filtered through Celite, rinsing with ethyl acetate (100 mL). To the filtrate was added ˜400 mL of a solution of saturated aqueous ammonium chloride and concentrated ammonium hydroxide (prepared by adding ammonium hydroxide to a saturated aqueous solution of ammonium chloride until pH=8). The mixture was stirred for 1 hour. The layers were then separated. The organic layer was washed with water and brine, dried over sodium sulfate, filtered and concentrated in vacuo. To the residue was added methanol (40 mL) and the mixture was stirred overnight. The mixture was filtered and the solid was dried in vacuo to give methyl 3-cyano-1H-indazole-6-carboxylate as a tan solid (1.47 g, 73%). 1H NMR (400 MHz, DMSO-d6, δ): 13.40 (br. s., 1H), 8.25 (s, 1H), 7.94 (d, J=8.6 Hz, 1H), 7.83 (d, J=8.4 Hz, 1H), 3.88 (s, 3H).

Workup

  1. customwas purged with nitrogen for 15 minutes
  2. temperatureThe reaction mixture was cooled
  3. additiondiluted with ethyl acetate (250 mL)
  4. filtrationfiltered through Celite
  5. washrinsing with ethyl acetate (100 mL)
  6. additionTo the filtrate was added ˜400 mL of a solution of saturated aqueous ammonium chloride and concentrated ammonium hydroxide (
  7. customprepared
  8. stirringThe mixture was stirred for 1 hour
  9. customThe layers were then separated
  10. washThe organic layer was washed with water and brine
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. additionTo the residue was added methanol (40 mL)
  15. stirringthe mixture was stirred overnight
  16. filtrationThe mixture was filtered
  17. customthe solid was dried in vacuo

Sources & evidence

ORD record
ord-6b206ac5e3c04ef48cdde31da2356d79
Source dataset
uspto-grants-2015_03
Patent number
US08993586B2

Reaction notes

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