1-Methyl-4-nitro-3-propyl-1H-pyrazole-5-carboxylic acid

• CAS: 139756-00-6
• Catalog Number: ACM139756006
• Category: Main Products
• Molecular Weight: 213.19
• Molecular Formula: C₈H₁₁N₃O₄
• Synonyms: 1-METHYL-4-NITRO-3-PROPYL-1H-PYRAZOLE-5-CARBOXYLIC ACID;2-METHYL-4-NITRO-5-PROPYL-2H-PYRAZOLE-3-CARBOXYLIC ACID;1-METHYL-4-NITRO-3-PROPYL-1H-PYRAZOL;1-Methyl-4-nitro-3-propyl-1H-pyrazole;1-Methyl-4-nitro-3-propyl-1H-pyrazole-5-carboxylic acid ,97%
• IUPAC Name: 2-methyl-4-nitro-5-propylpyrazole-3-carboxylic acid
• Canonical SMILES: CCCC1=NN(C(=C1[N+](=O)[O-])C(=O)O)C
• InChI Key: GFORSNBMYCLGIE-UHFFFAOYSA-N
• Boiling Point: 392.7ºC at 760mmHg
• Flash Point: 191.3ºC
• Density: 1.45g/cm³
• Appearance: Yellow to orange solid
• Exact Mass: 213.07500

Case Study

1-Methyl-4-Nitro-3-Propyl-1H-Pyrazole-5-Carboxylic Acid for the Synthesis of Sildenafil

Dale, David J., et al. Organic Process Research & Development, 2000, 4(1), 17-22.

This work reports a case of chemical development of sildenafil, where 1-methyl-4-nitro-3-propyl-1H-pyrazole-5-carboxylic acid is an important intermediate.
Synthesis route of sildenafil from 1-methyl-4-nitro-3-propyl-1H-pyrazole-5-carboxylic acid
· Synthesis of 1-Methyl-4-nitro-3-propyl-1H-pyrazole-5-carboxamide (3): A slurry of 1-methyl-4-nitro-3-propyl-1H-pyrazole-5-carboxylic acid (2) (1 kg, 4.69 mol) was prepared in toluene (5 L), to which a catalytic amount of dimethylformamide (37 mL) was added. The mixture was heated to 50 °C, and thionyl chloride (0.544 L, 7.5 mol) was introduced over a 10-minute period. Once the addition was completed, the reaction was stirred and maintained at 55-60 °C for 6 hours. The mixture underwent vacuum distillation (with a vessel temperature of 55 to 65 °C) to remove 0.5 L of solvent. After cooling to 20 °C, a cold (5 °C) concentrated ammonia solution (6 L) was added over 100 minutes. The resultant precipitate was granulated, collected by filtration, washed with water (2 × 2 L), and dried at 50 °C, yielding an off-white solid (0.92 kg, 92.3%).
· Synthesis of 4-Amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide (12): The nitropyrazole (3) (237.7 g, 1.12 mol) was suspended in ethyl acetate (2.02 L), and 47.5 g of 5% palladium on carbon was added. The mixture was hydrogenated at 50 °C and 50 psi for 4 hours until hydrogen uptake was complete. Following cooling, the catalyst was filtered out and washed with ethyl acetate, resulting in an ethyl acetate solution of the desired compound, which was subsequently used in the next step.