Acetic Acid → 1-(4-Ethoxy-2,6-difluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]-pyrazole-3-carboximidamide

HRID 1482922Notes

Reaction equation

HRID 1482922 reaction equation
[CH2:1]([O:3][C:4]1[CH:20]=[C:19]([F:21])[C:7]([CH2:8][N:9]2[C:13]3[CH2:14][CH2:15][CH2:16][C:12]=3[C:11]([C:17]#[N:18])=[N:10]2)=[C:6]([F:22])[CH:5]=1)[CH3:2].C[O-].[Na+].C(O)(=O)C.[Cl-].[NH4+:31]>CO>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([F:22])[C:7]([CH2:8][N:9]2[C:13]3[CH2:14][CH2:15][CH2:16][C:12]=3[C:11]([C:17](=[NH:31])[NH2:18])=[N:10]2)=[C:19]([F:21])[CH:20]=1)[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 25517Ammonium ChlorideHCID 10942334Sodium MethoxideHCID 900127051-(4-Ethoxy-2,6-difluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]-pyrazole-3-carbonitrile

Product 1

HCID 900127521-(4-Ethoxy-2,6-difluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]-pyrazole-3-carboximidamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

7.73 g of 1-(4-ethoxy-2,6-difluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]-pyrazole-3-carbonitrile 1-1-1 (25.5 mmol, 1.00 eq) were suspended in 100 mL methanol. 7.65 mL sodium methanolate in methanol (2.23 g, 41.3 mmol, 1.62 eq.) were added at rt. The reaction mixture was stirred for 4 h at rt. 2.36 mL acetic acid (2.45 g, 41.3 mmol, 1.62 eq.) and 2.05 g ammonium chloride (38.2 mmol, 1.50 eq.) were added and the reaction mixture was stirred at 50° C. for two days. The mixture was concentrated in vacuo and the residue was filtered off and washed with methanol. The filtrate was suspended in water and aqueous hydrochloric acid (4N). DCM was added, the aqueous layer was washed with DCM twice. To the aqueous layer aqueous sodiumhydroxid solution (2N) was added to reach pH 12. The aqueous layer was extracted with DCM/isopropanol (4:1) three times. The united organic layers were dried over a silicone filter, concentrated in vacuo to provide 2.67 g (7.99 mmol, 31.3%) of analytically pure target compound.

Workup

  1. stirringthe reaction mixture was stirred at 50° C. for two days
  2. concentrationThe mixture was concentrated in vacuo
  3. filtrationthe residue was filtered off
  4. washwashed with methanol
  5. additionDCM was added
  6. washthe aqueous layer was washed with DCM twice
  7. additionTo the aqueous layer aqueous sodiumhydroxid solution (2N) was added
  8. extractionThe aqueous layer was extracted with DCM/isopropanol (4:1) three times
  9. dry with materialThe united organic layers were dried over a silicone
  10. filtrationfilter
  11. concentrationconcentrated in vacuo
  12. customto provide 2.67 g (7.99 mmol, 31.3%) of analytically pure target compound

Sources & evidence

ORD record
ord-eb1608db11044b0f95acb59a26bd7c17
Source dataset
uspto-grants-2016_08
Patent number
US09416125B2

Reaction notes

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