4-Amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide → Sildenafil

Participants

Reaction Conditions

Reaction Steps

A solution of xylene (60 mL) containing 1-(4-ethoxy-3-formylphenylsulfonyl)-4-methylpiperazine (4.0 g, 0.013 mol, prepared analogously to the methods described in DE 24 44 720) and 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide (Example 37 of EP 0463756) (2.6 g, 0.014 mol) was submitted to 46 hours at 200° C. and 34.5 kPa (5 psi). The reaction was allowed to cool and the catalyst (10% Pd/C, 3.1 g, 50% w/w) was added. The reaction was heated at 200° C. under 34.5 kPa (5 psi) of pressure for a further 12 hours. The catalyst was recovered by filtration and the organic solvent removed in vacuo to give 4.2 g of crude product, which was purified by trituration in methyl ethyl ketone (MEK). This yielded 3.3 g (53%) of the title compound as an off-white solid.

Provenance & Evidence