1H-Imidazole-5-carboxylic acid

Imidazole-4-carboxylic acid is under investigation in clinical trial NCT00583895 (Safety and Efficacy Study of Imcooh Cream in Patients Suffering From Moderate Atopic Dermatitis).

The mass ratio of 1 H-imidazole-4-carboxylic acid ethyl ester to potassium hydroxide solution was 1: 2.2, the reaction temperature was 30 After the completion of the reaction, the sulfuric acid solution is added, the pH is adjusted to 1, and the crude product is recrystallized from the recrystallization solvent to obtain 1H-imidazole-4-carboxylic acid.The 2.2g imidazole-4-carboxylic acid ethyl ester in 30 ml water, raising the temperature to 65 °C, stirring next adds by drops 3.3g the mass concentration is 20percent of the reacted with an aqueous solution of KOH to the end point.Adding dilute hydrochloric acid wash filters after adjusting pH to obtain 1H-imidazole-4-carboxylic acid.The nitroimidazole carboxylic acid was readily obtained by nitration of imidazole carboxylic acid (Scheme 2) as previously described [11, 23].1H-1-(Triphenylmethyl)-1H-To a RT solution of 1H-Using the methods of Examples 5 and 6, substituting Part E compound was added (0.20 g, 0.49 mmol) and the reaction was run at 85° C. (oil bath temperature) for 2 hours. DMSO was removed in vacuo (vacuum pump, dry ice-cooled receiver flask). Ethyl acetate (30 mL) and 1M HC1 were added. The ethyl acetate layer was washed 3 times with 1M HC1, 3 times with saturated aqueous K2 CO3 solution, brine, dried over Na2 SO4 and concentrated to yield 0.39 g of a viscous yellow oil. Flash chromatography on 27 g of silica gel (99.5/0.5 CH2 Cl2 /CH3 OH) yielded 0.16 g of title compound as a white crystalline solid. Also isolated was 0.16 g of unconsumed Part C compound.EXAMPLE 10 The reaction of was carried out using 10 moles of potassium hydroxide instead of potassium carbonate. 510 g (58percent of theory) of In a 250 mL three-necked flask equipped with a reflux unit, Dissolve 0.008 mol of 1H-In a 25 mL round bottom flask, compound 18 (70 mg, 0.12 mmol) was dissolved in MeOH (3 mL)The reaction was terminated by TLC, and the solvent was removed under reduced pressure to give a white residue.The residue was dissolved in DMF (2 mL).Adding to a reaction solution of compound 23 (16 mg, 0.14 mmol), DIPEA (61 mg, 0.47 mmol) and HATU (58 mg, 0.15 mmol) in DMF (3 mL)Stir at room temperature for 4 hours, The solvent was removed under reduced pressure.The residue was added to trifluoroacetic acid (3 mL) and stirred at room temperature for 2 hours.The solvent was removed under reduced pressure.The residue was prepared in reverse by C18 high performance liquid chromatography.The mobile phase was acetonitrile (0.1percent trifluoroacetic acid) and water (0.1percent trifluoroacetic acid) to give compound 25 (12 mg, a three-step reaction yield 29percent).White solid.

Molecular Weight:112.09
XLogP3:-0.1
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:112.027277375
Monoisotopic Mass:112.027277375
Topological Polar Surface Area:66
Heavy Atom Count:8
Complexity:104
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes