Acetaldehyde → N-Ethyl-3-(4-fluorophenyl)-1H-indazol-5-amine

HRID 1349599Notes

Reaction equation

HRID 1349599 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([N+:17]([O-])=O)[CH:15]=3)[N:10](COCCOC)[N:9]=2)=[CH:4][CH:3]=1.[CH:26](=O)[CH3:27]>C(O)C.[Pd].[C]>[CH2:26]([NH:17][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][CH:13]=1)[NH:10][N:9]=[C:8]2[C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)[CH3:27]

Participants

5

Reactant 2

HCID 177AcetaldehydeHCID 22479987HCID 22479987, compound

Product 1

HCID 22480152N-Ethyl-3-(4-fluorophenyl)-1H-indazol-5-amineYield 11%

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 702EthanolSolvent

Procedure

To a solution of 1-{[3-(4-fluorophenyl)-5-nitro(1H-indazolyl)]methoxy}-2-methoxyethane (100 mg, 0.29 mmol) in ethanol (30 mL, containing a contaminant of acetaldehyde) was added a scoup of Pd/carbon. The reaction was stirred overnight at room temperature under an atmosphere of hydrogen. It was filtered over celite and the solution concentrated to an oil. The oil was taken up in methanol (20 mL) and 6N HCl (20 mL) and heated to 75° C. for 3 hours. The solution was concentrated under vacuo, added to saturated bicarbonate (100 mL), and extracted with ethyl acetate (3×30 mL). The organic layers were dried (Na2SO4), concentrated to an oil and chromatographed on silica gel, eluting with 50% ethyl acetate/hexane to give the title compound (8 mg, 11% yield). 1H NMR (CDCl3) δ 10.4 (br s, 1H), 7.91 (dd, 2H), 7.26–7.17 (m, 3H), 6.99 (s, 1H), 6.84 (dd, 1H), 3.21 (q, 2H), 1.31 (t, 3H); ES-MS (m/z) 256 [M+1]+.

Workup

  1. filtrationIt was filtered over celite
  2. concentrationthe solution concentrated to an oil
  3. temperature6N HCl (20 mL) and heated to 75° C. for 3 hours
  4. concentrationThe solution was concentrated under vacuo
  5. additionadded to saturated bicarbonate (100 mL)
  6. extractionextracted with ethyl acetate (3×30 mL)
  7. dry with materialThe organic layers were dried (Na2SO4)
  8. concentrationconcentrated to an oil
  9. customchromatographed on silica gel
  10. washeluting with 50% ethyl acetate/hexane

Sources & evidence

ORD record
ord-53c1940ec60f4fb29a42f8044dbedba6
Source dataset
uspto-grants-2007_05
Patent number
US07211594B2

Reaction notes

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