Diethyl (ethoxymethylene)malonate → diethyl N-(1-phenyl-pyrazol-3-yl)-aminomethylenemalonate

HRID 1979746Notes

Reaction equation

HRID 1979746 reaction equation
[C:1]1([N:7]2[CH:11]=[CH:10][C:9]([NH2:12])=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(O[CH:16]=[C:17]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:18]([O:20][CH2:21][CH3:22])=[O:19])C>C(O)C>[C:1]1([N:7]2[CH:11]=[CH:10][C:9]([NH:12][CH:16]=[C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:23]([O:25][CH2:26][CH3:27])=[O:24])=[N:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 6871Diethyl (ethoxymethylene)malonateHCID 5943201-phenyl-1H-pyrazol-3-amine

Product 1

HCID 13216660diethyl N-(1-phenyl-pyrazol-3-yl)-aminomethylenemalonate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

1-phenyl-3-amino-pyrazole, m.p. 90°-91° C. (18 g) was reacted with diethyl ethoxymethylenemalonate (29.3 g) in anhydrous ethanol (180 ml) at the reflux temperature for 15 hours. After cooling the solution was evaporated in vacuo to dryness: the residue was dissolved in isopropyl ether (200 ml) and decolorized by charcoal. Crystallization obtained by dilution with hexane gave diethyl N-(1-phenyl-pyrazol-3-yl)-aminomethylenemalonate, m.p. 81°-82° C. (31 g), which was reacted with polyphosphoric acid (13 g; 6.1 g of P2O5 and 6.9 g of H3PO4) and POCl3 (57 g) under stirring at the reflux temperature for 30 minutes. After cooling the reaction mixture was diluted with ice water and then the solution was decolorized, with charcoal: neutralization with 35% NaOH gave a precipitate which was filtered and washed with water. Washing with hexane gave 1-phenyl-7-oxo-1H,7H-pyrazolo[1,5-a]pyrimidine-6-carboxylic acid, ethyl ester, m.p. 187°-190° C. (24.2 g), which was hydrolized by heating with a mixture 1:1 of 37% HCl:acetic acid (1.2 l) at the reflux temperature for 4 hours. After cooling the reaction mixture was neutralized to pH=6 with 35% NaOH and the precipitate was filtered and washed with water: crystallization from isopropyl alcohol gave 9.7 g of 1-phenyl-7-oxo-1H,7H-pyrazolo[1,5-a]pyrimidine-6-carboxylic acid m.p. 185°-190° C. dec., N.M.R. (DMSO-d6) δ p.p.m.: 6.94 (d) (1H, C-3 proton), 7.59 (s) (5H, phenyl protons), 8.74 (d) (1H, C-2 proton), 8.81 (s) (C-5 proton).

Workup

  1. temperatureAfter cooling the solution
  2. customwas evaporated in vacuo to dryness
  3. dissolutionthe residue was dissolved in isopropyl ether (200 ml)
  4. customCrystallization
  5. customobtained by dilution with hexane

Sources & evidence

ORD record
ord-1d13c87cb6c14784a70cabcbe650429f
Source dataset
uspto-grants-1984_11
Patent number
US04482555

Reaction notes

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