Ethyl 2-chloroacetoacetate → 3-(Cyclopropylamino)-5-methyl-1H-pyrazole-4-carboxylic acid, ethyl ester hydrochloride

HRID 1761553Notes

Reaction equation

HRID 1761553 reaction equation
[CH:1]1([NH:4][C:5](=S)[NH:6][NH2:7])[CH2:3][CH2:2]1.[Cl:9][CH:10]([C:16]([CH3:18])=O)[C:11]([O:13][CH2:14][CH3:15])=[O:12]>Cl>[ClH:9].[CH:1]1([NH:4][C:5]2[C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:16]([CH3:18])[NH:7][N:6]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 11858Ethyl 2-chloroacetoacetateHCID 18081583-Amino-1-cyclopropylthiourea

Product 1

HCID 145007133-(Cyclopropylamino)-5-methyl-1H-pyrazole-4-carboxylic acid, ethyl ester hydrochlorideYield 32.5%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

A stirred slurry of 10.4 g (0.079 mole) of 4-cyclopropyl-3-thiosemicarbazide under nitrogen atmosphere was treated with 13 g (0.079 mole) of ethyl 2-chloroacetoacetate, stirred at ambient temperature for 1 hr, treated with 30 mL of 2N ethanolic hydrogen chloride and heated to reflux. The reaction mixture was allowed to cool to ambient temperature while stirring for ~72 hr. the sulfur residue was removed by filtration and the filtrate concentrated in vacuo to an orange oil which solidified. Recrystallization twice from acetone gave 7.4 g of large blade-like crystals, after drying for 2 hr at 98° C. under reduced pressure, mp 147°-148.5° C. The filtrates gave an additional 6 g of crude product. The 2 solids were combined and recrystallized from methyl ethyl ketone to give 6.3 g of white crystalline powder, mp 151°-152° C.

Workup

  1. temperatureheated to reflux
  2. temperatureto cool to ambient temperature
  3. stirringwhile stirring for ~72 hr
  4. customthe sulfur residue was removed by filtration
  5. concentrationthe filtrate concentrated in vacuo to an orange oil which
  6. customRecrystallization twice from acetone
  7. customgave 7.4 g of large blade-like crystals
  8. customafter drying for 2 hr at 98° C. under reduced pressure, mp 147°-148.5° C
  9. customThe filtrates gave an additional 6 g of crude product
  10. customrecrystallized from methyl ethyl ketone

Sources & evidence

ORD record
ord-ca1a2f8323c147e5936ad409a46fadc1
Source dataset
uspto-grants-1989_05
Patent number
US04826866

Reaction notes

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