Synthesis of the Mutagenic 2-Amino-1,6-dimethylimidazo[4,5-b]pyridine (1,6-DMIP) and Five of Its Isomers

Lindström, Stefan B.; Ahmad, Tania; Grivas, Spiros

doi:10.3987/com-93-6573

Cited by 9 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Серед низки його похідних виявлено антагоністи рецептора ангіотензину ІІ [1], тромбоксан А 2 простагландинового Н 2 рецептора [2], інгібітори гідролази лейкотриєну А 4 [3], специфічної серин\треонін протеїнкінази [4,5] та дипептидилпептинази [6]. При цьому також варто звернути увагу і на наявність мутагенних властивостей у деяких 2-аміноімідазо [4,5-b]піридинів [7,8] та їх конденсованих похідних [9,10], які можуть утворюватися в процесі термічного оброблення м'яса і риби.…”

unclassified

Convenient approaches to the synthesis of 6-amino- and 6-oxoimidazo[4,5-b]pyrazolo[3,4-e]pyridines

Yakovenko¹,

Вовк²

2021

J. org. pharm. chem.

View full text Add to dashboard Cite

Aim. To develop convenient approaches to the synthesis of 6-amino- and 6-oxoimidazo[4,5-b]pyrazolo[3,4-e]pyridines as promising biologically active scaﬀolds.Results and discussion. It has been found that cyclocondensation of N-Boc-4-aminopyrazole-5-carbaldehydes with creatinine can be used as an eﬀective method for obtaining 6-aminoimidazo[4,5-b]pyrazolo[3,4-e]pyridines previously unknown. For the synthesis of their 6-oxoanalogs, the reaction of 5-aminopyrazolo[4,3-b]pyridine-6-carboxylic acids used in a modifed Curtius rearrangement with diphenylphosphorylazide was successful. This method was implemented through the stage of the intermediate aminoisocyanates formation.Experimental part. The reaction of N-Boc-4-aminopyrazole-5-carbaldehydes with creatinine in the presence of pyrrolidine as a catalyst in reﬂuxing acetic acid allowed to obtain 6-aminoimidazo[4,5-b]pirazolo[3,4-e]pyridines with the yields of 54 – 70 %. The structure of the compounds synthesized was proven by spectral measurements. In the 1H NMR spectra there were singlets of H-3 (7.63 – 7.88 ppm) and H-8 (7.87 – 8.26 ppm) protons, as well as broad singlets of the NH2 group in the range of 7.05 – 7.21 ppm. Heating of 5-aminopyrazolo[4,3-b]pyridine-6-carboxylic acids with triethylamine and diphenylphosphorylazide in dioxane for 6 hours gave 1-substituted imidazo[4,5-b]pyrazolo[3,4-е]pyridine-6(5Н)-ones with the yields of 67 – 80 %. The IR-spectra of the compounds synthesized were characterized by the absorption bands of the C=O (1705 – 1708 cm-1) and NH (3275 – 3281 cm-1) groups. 1H NMR-spectra were characterized by singlets of H-3 and H-8 protons in the intervals of 7.43 – 8.08 ppm and 7.92 – 8.32 ppm respectively, as well as by two broad singlets of NH-protons in the ranges of 10.90 – 11.12 ppm and 11.25 – 11.37 ppm.Conclusions. Eﬀective approaches to the synthesis of new promising heterocyclic systems of 6-amino- and6-oxoimidazo[4,5-b]pirazolo[3,4-e]pyridines have been developed. Cyclocondensations of N-Boc-4-aminopyrazole-5-carbaldehydes with creatinine and 5-aminopyrazolo[4,3-b]pyridine-6-carboxylic acids with diphenylphosphorylazide have been proven to be convenient ways to obtain these compounds with good yields.Key words: N-Boc-4-aminopyrazole-5-carbaldehyde; creatinine; 5-aminopyrazolo[4,3-b]pyridine-6-carboxylic acid; diphenylphosphorylazide; 6-amino(oxo)imidazo[4,5-b]pyrazolo[3,4-e]pyridines;cyclocondensation

show abstract