Potassium Carbonate → 3-iodo-1-((1-methyl-1H-pyrazol-3-yl)methyl)-4-nitro-1H-indazole

HRID 79377Notes

Reaction equation

HRID 79377 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][C:4]([CH2:7]O)=[N:3]1.S(Cl)(Cl)=O.[I:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][C:21]=2[N+:23]([O-:25])=[O:24])[NH:16][N:15]=1.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.CN(C=O)C>[I:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][C:21]=2[N+:23]([O-:25])=[O:24])[N:16]([CH2:7][C:4]2[CH:5]=[CH:6][N:2]([CH3:1])[N:3]=2)[N:15]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 12845046(1-methyl-1H-pyrazol-3-yl)methanolHCID 178526562HCID 178526562, compound

Product 1

HCID 672615133-iodo-1-((1-methyl-1H-pyrazol-3-yl)methyl)-4-nitro-1H-indazoleYield 74.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To (1-methyl-1H-pyrazol-3-yl)methanol (2.01 g, 17.93 mmol) in DCM (80 mL) at 0° C. was cautiously added thionyl chloride (10.43 mL, 143.4 mmol). The cold bath was removed and the reaction mixture was stirred at ambient temperature for 3 hours. The reaction mixture was concentrated under reduced pressure. The residual yellow solid was diluted with DMF (30 mL). 3-Iodo-4-nitro-1H-indazole (5.181 g, 17.93 mmol) and K2CO3 (7.432 g, 53.78 mmol) were added to the DMF solution. The reaction mixture was stirred for 20 hours, and concentrated under reduced pressure to remove most of the DMF. The residue was diluted with DCM (100 mL) and washed with H2O. The organic phase was dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by silica gel chromatography (EtOAc/Hexane 1:3) to provide the product (5.11 g).

Workup

  1. customat 0° C.
  2. customThe cold bath was removed
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additionThe residual yellow solid was diluted with DMF (30 mL)
  5. stirringThe reaction mixture was stirred for 20 hours
  6. concentrationconcentrated under reduced pressure
  7. customto remove most of the DMF
  8. additionThe residue was diluted with DCM (100 mL)
  9. washwashed with H2O
  10. dry with materialThe organic phase was dried (Na2SO4)
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by silica gel chromatography (EtOAc/Hexane 1:3)

Sources & evidence

ORD record
ord-633e65df7b164fa2b174d505f013a6e6
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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