4-Nitropyrazole-3-carboxylicacid

White to off-white crystalline powder

In a 250 mL round bottom flask, 7.0 g (36.6 mmol) of crude I-n was added. 4-((tetrahydro-2H-[1, 4]dioxo[2, 3-c]pyrrole-6(3H)-yl)methyl)benzene-1, 2-diamine (2.19 g, 8.78 mmol), 4-nitro-1H-pyrrole-3-carboxylic acid (1.24 g, 7.91 mmol), EDCl (1.68 g, 8.78 mmol) and HOBt (1.19 g, 8.78 mmol)It was stirred at room temperature overnight in DMF (22 mL). The solvent was removed under reduced pressure.AcOH (35 mL) was added to the residue and heated to reflux for 3.5 hr.The solvent was removed under reduced pressure and purified by column chromatography (dichloromethane/methanol (v/v) = 10/1).The product was obtained (1.65 g, 51percent).The compound 2-amino-4-(morpholinomethyl)phenol (2.54 g, 16 mmol) was dissolved.In DMF (15mL), Add 4-nitro-1 hydrogen-pyrazole-3-carboxylic acid (3.4 g, 16 mmol)With HATU (7.4 g, 19.6 mmol), react at room temperature overnight.After the reaction was completed, the solvent was evaporated and ethyl acetate (3×50 mL).Washed with water (2 × 50 mL), dried over anhydrous sodium sulfate (10 g), Dry to give the crude product (1.5 g), which was used directly to the next step.4-(2-Thio-5-azabicyclo[2.2.1]heptane-5-ylmethyl)benzene-1, 2-diamine (0.7 g, 3 mmol), 4-nitro-1 hydrogen -pyrazole-3-carboxylic acid (0.47 g, 3 mmol)Dissolved in DMF (15 mL) followed by EDCI (0.63 g, 3.3 mmol)HOBt (0.45 g, 3.3 mmol) was stirred at room temperature for 24 hours.The solvent was removed under reduced pressure, and acetic acid (20 mL) was evaporated.After completion of the reaction, concentration and purification by column (dichloromethane/methanol (v/v) = 10/1), The product was obtained (0.5 g, 50percent).4-(2-oxa-5-heterobicyclo[2.2.1]-heptan-5-ylmethyl)phenyl-1, 2-diamine(0.85g, 3.88mmol), 4-nitro-1H-pyrrole-3-carboxylic acid (0.58g, 3.69mmol), EDCl (0.78g, 4.06mmol) and HOBt (0.55g, 4.06mmol)DMF (10 mL) was stirred at room temperature overnight. The solvent was removed under reduced pressure.AcOH (16 mL) was added to the residue and heated to reflux for 3.5 hr.The solvent was removed under reduced pressure and purified by column (dichloromethane/methanol (v/v) = 10/1).A yellow solid (0.79 g, 63percent) was obtained.4-(octahydrocyclopentane[c]pyrrolylmethyl)-phenyl-1, 2-diamine (4.0 g, 17.32 mmol), 4-Nitro-1H-pyrrole-3-carboxylic acid (0.65 g, 4.12 mmol), EDCI (0.87 g, 4.53 mmol) and HOBt (0.61 g, 4, 53 mmol) were added to the reaction mixture.Stir at room temperature overnight.The solvent was removed under reduced pressure and ethyl acetate (20 mL) was evaporated. The solvent was removed under reduced pressure and purified by column to afford product (1.10 g, 54percent).4-Nitro-1H-pyrrole-3-carboxylic acid (0.65 g, 4.12 mmol), EDCI (0.87 g, 4.53 mmol) and HOBt (0.61 g, 4.53 mmol) were added to the reaction mixture.Stir at room temperature overnight. The solvent was removed under reduced pressure.AcOH (20 mL) was added to the residue, and the mixture was refluxed for 3 hr.The solvent was removed under reduced pressure and purified by column (dichloromethane/methanol (v/v) = 10/1).The product was obtained (2.10g, >100percent).

Molecular Weight:157.08
XLogP3:-0.1
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:1
Exact Mass:157.01235559
Monoisotopic Mass:157.01235559
Topological Polar Surface Area:112
Heavy Atom Count:11
Complexity:188
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes