Ethyl 5-amino-1-methyl-1H-pyrazole-4-carboxylate → HCID 135713177, compound

HRID 241950Notes

Reaction equation

HRID 241950 reaction equation
[O-][CH2:2][CH3:3].[Na+].C([C:7](CC)([C:11]([O-:13])=O)[C:8]([O-:10])=[O:9])C.[NH2:16][C:17]1[N:21]([CH3:22])[N:20]=[CH:19][C:18]=1[C:23]([O:25]CC)=O>C(O)C>[OH:25][C:23]1[C:18]2[CH:19]=[N:20][N:21]([CH3:22])[C:17]=2[NH:16][C:11](=[O:13])[C:7]=1[C:8]([O:10][CH2:2][CH3:3])=[O:9]

Participants

5

Reactant 3

HCID 271299Ethyl 5-amino-1-methyl-1H-pyrazole-4-carboxylateHCID 2723922Sodium ethoxideHCID 69515632,2-Diethylpropanedioate

Product 1

HCID 135713177HCID 135713177, compoundYield 64.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Sodium ethoxide (95%, 83 g, 1.18 moles) was dissolved in 175 mL of absolute ethanol, following the protocol described in J. Heterocyclic Chem. (1978) 15:319 with some modifications. Diethylmalonate 2 (184.6 g, 1.18 moles) was added and stirred at room temperature for 10 minutes. Ethyl 5-amino-1-methylpyrazole-4-carboxylate 1 (50 g, 0.295 moles) was added slowly and the resulting solution refluxed overnight at 100° C. During the reflux period, an off-white solid began to form. The solution was evaporated to dryness on a rotary evaporator and the residue dissolved in a minimum amount of water. Upon acidification (pH 2) of the aqueous solution with concentrated hydrochloric acid, the resulting precipitate was filtered and recrystallized from acetic acid-water to give 3 as a white solid (˜45 g, 64%). NMR (trifluoroacetic acid): δ 1.60 (t.3H.J=7 Hz, CH3 of ester), 4.22 (s, 3H, N—CH3), 4.80 (q, 2H, J=7 hz, CH2), 8.49 (s, 1H, H-3)

Workup

  1. temperaturethe resulting solution refluxed overnight at 100° C
  2. customto form
  3. customThe solution was evaporated to dryness on a rotary evaporator
  4. dissolutionthe residue dissolved in a minimum amount of water
  5. filtrationUpon acidification (pH 2) of the aqueous solution with concentrated hydrochloric acid, the resulting precipitate was filtered
  6. customrecrystallized from acetic acid-water

Sources & evidence

ORD record
ord-23aacc74fbc34f6980762a89567fabcc
Source dataset
uspto-grants-2014_02
Patent number
US08653098B2

Reaction notes

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