Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Mar 23:11:385-91.
doi: 10.3762/bjoc.11.44. eCollection 2015.

The reactions of 2-ethoxymethylidene-3-oxo esters and their analogues with 5-aminotetrazole as a way to novel azaheterocycles

Marina V Goryaeva  1 , Yanina V Burgart  1 , Marina A Ezhikova  1 , Mikhail I Kodess  1 , Viktor I Saloutin  1
Affiliations

The reactions of 2-ethoxymethylidene-3-oxo esters and their analogues with 5-aminotetrazole as a way to novel azaheterocycles

Marina V Goryaeva et al. Beilstein J Org Chem. .

Abstract

The interaction of 2-ethoxymethylidene-3-oxo esters and their analogues with 5-aminotetrazole is an efficient synthetic approach to novel azaheterocycles. 2-Ethoxymethylidene-3-oxo esters bearing alkyl substituents react with 5-aminotetrazole to form ethyl 2-azido-4-alkylpyrimidine-5-carboxylates which are capable of subsequent nucleophilic substitution. The use of diethyl 2-ethoxymethylidenemalonate in this reaction resulted in ethyl 7-hydroxytetrazolo[1,5-a]pyrimidine-6-carboxylate, while ethyl 2-ethoxymethylidenecyanoacetate yielded 5-[2,6-diamino-3,5-bis(ethoxycarbonyl)pyridinium-1-yl]tetrazol-1-ide through an alternative pathway. Ethyl 2-benzoyl-3-ethoxyprop-2-enoate reacted with 5-aminotetrazole by two reaction routes to form ethyl 2-benzoyl-3-(1H-tetrazol-5-ylamino)prop-2-enoate and ethyl 7-(1-ethoxy-1,3-dioxo-3-phenylpropan-2-yl)-5-phenyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate.

Keywords: 2-ethoxymethylidene-3-oxo esters; 5-aminotetrazole; cyclisation; diethyl 2-ethoxymethylidenemalonate; ethyl 2-ethoxymethylidenecyanoacetate.

PubMed Disclaimer

Figures

Scheme 1
Scheme 1
Interaction of 2-ethoxymethylidene-3-oxo esters 1a–c with 5-AT. R = CF3 (a), (CF2)2H (b), Me (c). Conditions, i: TFE, Δ, 32–38 h; ii: Air, rt, 12 days; iii: EtOH, rt, 9 days.
Scheme 2
Scheme 2
Synthesis of pyrimidines 4a,b and 5. R= CF3 (a), (CF2)2H (b). Conditions: i: 1,4-dioxane, NaOAc, Δ, 16–18 h; ii DMF, NaOAc, 80 °C, 24–26 h; iii: 1,4-dioxane, Et3N, Δ, 40 h.
Figure 1
Figure 1
X-ray crystal structure of compound 5 (ORTEP drawing, 50% probability level).
Scheme 3
Scheme 3
Interaction of 2-ethoxymethylidene malonate 1e with 5-AT. Conditions: i: EtOH, Et3N, Δ; ii: EtOH, Δ.
Scheme 4
Scheme 4
The reaction of 3-oxo ester 1d with 5-AT. Conditions, i: TFE, Δ, 48 h.
Scheme 5
Scheme 5
Interaction of ester 1f with 5-AT. Conditions i: EtOH (or TFE), Et3N, Δ, 40–60 min; ii: AcOH (or EtOH, AcOH), Δ, 32 h.
Figure 2
Figure 2
X-ray crystal structure of compound 11 (ORTEP drawing, 50% probability level).
See this image and copyright information in PMC

References

    1. Kudyakova Yu S, Bazhin D N, Goryaeva M V, Burgart Y V, Saloutin V I. Russ Chem Rev. 2014;83:120–142. doi: 10.1070/RC2014v083n02ABEH004388. - DOI
    1. Ram V J, Pratibha S, Singh S K, Kandpal M, Tekwani B L. Bioorg Med Chem Lett. 1997;7:1087–1090. doi: 10.1016/S0960-894X(97)00166-2. - DOI
    1. Kuribayashi S, Goto K, Naito S, Kamataki T, Yamazaki H. Chem Res Toxicol. 2009;22:323–331. doi: 10.1021/tx8003592. - DOI - PubMed
    1. Maddry J A, Ananthan S, Goldman R C, Hobrath J V, Kwong C D, Maddox C, Rasmussen L, Reynolds R C, Secrist J A, Sosa M I, et al. Tuberculosis. 2009;89:354–363. doi: 10.1016/j.tube.2009.07.006. - DOI - PMC - PubMed
    1. Ruisi G, Canfora L, Bruno G, Rotondo A, Mastropietro T F, Debbia E A, Girasolo M A, Megna B. J Organomet Chem. 2010;695:546–551. doi: 10.1016/j.jorganchem.2009.11.019. - DOI

LinkOut - more resources