Acetic Acid → HCID 2768374, compound

HRID 1720254Notes

Reaction equation

HRID 1720254 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][CH:3]=1.[C:11]([O:17][CH2:18][CH3:19])(=[O:16])[CH2:12][C:13]([CH3:15])=O.S([O-])([O-])(=O)=O.[Ca+2].C(O)(=O)C>C(O)C>[NH:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([NH:1][C:13]([CH3:15])=[CH:12][C:11]([O:17][CH2:18][CH3:19])=[O:16])[CH:10]=2)[CH:6]=[N:7]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8868Ethyl Acetoacetate3×HCID 24497Calcium Sulfate3×HCID 814231H-Indazol-6-amine2×

Product 1

HCID 2768374HCID 2768374, compoundYield 84.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a suspension of 6-aminoindazole (40.0 g, 0.30 mol) in absolute ethanol (500 ml) was added ethyl acetoacetate (70.37 g, 54 mol), calcium sulfate (CaSO4) (20 g) and acetic acid (2 ml). The reaction mixture was heated to reflux and after 24 hours more calcium sulfate (10 g) and ethyl acetoacetate (19 ml) was added and the reflux continued for another 24 hour period. It was necessary to add more CaSO4 (5 g) and ethyl acetoacetate (10 ml) and to reflux the reaction mixture for an additional 24 hours to complete the conversion of 6-aminoindazole to product. The solid was removed by filtration and the filtrate subjected to rotary evaporation. Ethanol was added and the slurry cooled in a refrigerator. The solid was collected by filtration, washed with hexanes and dried in a vacuum oven to give the cyclization precursor ethyl 3-(indazol-6-ylamino)but-2-enoate as a light brown solid (62.19 g, 84%).

Workup

  1. temperatureThe reaction mixture was heated
  2. additionwas added
  3. temperatureto reflux the reaction mixture for an additional 24 hours
  4. customThe solid was removed by filtration
  5. customthe filtrate subjected to rotary evaporation
  6. additionEthanol was added
  7. temperaturethe slurry cooled in a refrigerator
  8. filtrationThe solid was collected by filtration
  9. washwashed with hexanes
  10. customdried in a vacuum oven

Sources & evidence

ORD record
ord-1d6653d3e6264d07a68d4292778b2840
Source dataset
uspto-grants-1996_04
Patent number
US05506235

Reaction notes

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