Acetic Acid → 1-(4-methoxybenzyl)-1H-indazole-3-carboximidamide

HRID 1776389Notes

Reaction equation

HRID 1776389 reaction equation
[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([C:17]#[N:18])=[N:9]2)=[CH:5][CH:4]=1.C[O-].[Na+].[Cl-].[NH4+:25].C(O)(=O)C>CO>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([C:17](=[NH:25])[NH2:18])=[N:9]2)=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 25517Ammonium ChlorideHCID 10942334Sodium MethoxideHCID 867324141-(4-methoxybenzyl)-1H-indazole-3-carbonitrile

Product 1

HCID 867324151-(4-methoxybenzyl)-1H-indazole-3-carboximidamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

9.25 g of 1-(4-methoxybenzyl)-1H-indazole-3-carbonitrile (1-1-1, 35.1 mmol, 1 eq.) were suspended in 128 ml of dry methanol under a nitrogen atmosphere. 0.949 g (17.6 mmol, 0.5 eq.) of sodium methanolate were added. The reaction mixture was stirred for 18 hours at room temperature. To the resulting mixture were added 2.82 g (52.7 mmol, 1.5 eq.) of ammonium chloride and 1.0 ml (17.6 mmol, 0.5 eq.) of 100% acetic acid and stirred for 5 hours at 50° C. After cooling down at room temperature the mixture was concentrated in vacuo. The residue was partitioned between aq. half saturated sodium hydrogen carbonate solution and dichloromethane/isopropanol 4:1. The aqueous layer was extracted three times with dichloromethane/isopropanol 4:1. The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by flash chromatography to yield 6.45 g (23 mmol, 65.5%) of the analytically pure target compound.

Workup

  1. stirringstirred for 5 hours at 50° C
  2. temperatureAfter cooling down at room temperature the mixture
  3. concentrationwas concentrated in vacuo
  4. customThe residue was partitioned between aq. half saturated sodium hydrogen carbonate solution and dichloromethane/isopropanol 4:1
  5. extractionThe aqueous layer was extracted three times with dichloromethane/isopropanol 4:1
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography
  10. customto yield 6.45 g (23 mmol, 65.5%) of the analytically pure target compound

Sources & evidence

ORD record
ord-56aa86c1b25c41a1afa10e4f17124c99
Source dataset
uspto-grants-2016_02
Patent number
US09265763B2

Reaction notes

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