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

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Reaction Steps

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)

Provenance & Evidence