Synthesis and Transformations of Oxy Amides Derived from Cycloalka[ c ]- and Pyrano[3,4- c ]pyridines
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Synthesis and Transformations of Oxy Amides Derived from Cycloalka[c]- and Pyrano[3,4-c]pyridines S. N. Sirakanyana,*, S. G. Ghazaryanb, E. K. Hakobyana, and A. A. Hovakimyana a
Scientific Technological Center of Organic and Pharmaceutical Chemistry, National Academy of Sciences of Armenia, Yerevan, 0014 Armenia b
Armbiotechnology Scientific and Production Center, National Academy of Sciences of Armenia, Yerevan, 0056 Armenia *e-mail: [email protected] Received August 11, 2020; revised August 14, 2020; accepted August 19, 2020
Abstract—The alkylation of 3-hyroxycycloalka[c]- and 6-hydroxypyrano[3,4-c]pyridines with ethyl chloroacetate and ethyl 4-chlorobutanoate gave the corresponding oxy esters which were converted to amides by reaction with various amines. The synthesized acetamide derivatives underwent base-catalyzed Smiles type rearrangement to 3-aminotetrahydroquinolines or intramolecular cyclization to 1-aminofuro[2,3-b]isoquinolines, depending on the substituents on the amide nitrogen atom. Butanamide derivatives failed to react under similar conditions. Keywords: amino amides, furo[2,3-b]pyridines, Smiles rearrangement, oxoacetates, ethoxybutanoates
DOI: 10.1134/S1070428020100310 We previously reported that acetamides 3 containing a fused pyridine fragment undergo Smiles rearrangement by the action of sodium ethoxide to give the corresponding amino derivatives 4 or aminofuro[2,3-b]pyridinecarboxamides 5, depending on the substitution at the amide nitrogen atom [1–4]. In continuation of our studies in this field, herein we report the synthesis of new amino derivatives 4a–4d and amino amides 5a–5c. The starting compounds were acetates 2a and 2b which were prepared by alkylation of hydroxy derivatives 1 with ethyl chloroacetate. Compounds 2a and 2b were converted to amides 3a–3g by treatment with various amines (Scheme 1). From the theoretical viewpoint, it was interesting to perform similar transformations of analogous compounds with a longer carboxylic acid fragment (m = 2, 3). However, attempted alkylation of 1 with ethyl 3-chloropropanoate (m = 2) was unsuccessful. The alkylation of 1 [5] with ethyl 4-chlorobutanoate gave esters 2c–2e which were treated with various primary amines to afford amides 3h–3k. It should be noted that cyclic secondary amines failed to react with esters 2c–2e. Amides 3h–3k (m = 3) did not undergo Smiles rearrangement, and no corresponding amino derivatives 5 were obtained. It is well known that rearrangements
of this type occur when the oxygen and amide nitrogen atoms are separated by 2 or 3 carbon atoms [6–9]. The structure of the isolated compounds was confirmed by spectral data and elemental analyses. Esters 2a–2e (general procedure). Ethyl chloroacetate or ethyl 4-chlorobutanoate, 0.011 mol, was added dropwise with stirring to a suspension of 0.01 mol of compound 1 and 1.66 g (0.012 mol) of potassium carbonate in 50 mL of anhydrous DMF, and the mixture was heated at 75–80°C for 2 h. After cooling to room temperature, the mixture was poured into cold water, and
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