Purines. LIV. Intramolecular Cyclization of 9-Ethyl-1-(2-hydroxyethyl)adenine Caused by Nucleophiles : Formation of N^6,1-Ethanoadenine Derivatives

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Treatment of 9-ethy-1-(2-hydroxythyl)adenide hydrobromide (1a) in boiling N, N-dimethylformamide (DMF) with an excess of thiourea for 7 h or with an excess of ammonium thiocyanate for 3 h provided 3-ethyl-7,8-dihydro-3H-imidazo[2,1-i]purinium thiocyanate (8) in 51% or 58% yield, respectively. On treatment with an excess of triphenyl phosphite in boiling DMF for 20 min, 1 a underwent a similar cyclization to from the same tricycle, which was isolated in 81% yield (from 1 a)in the form of the perchlorate salt (12). A similar treatment of 1 a with triethyl phosphite furnished the 9-ethyl analogue (15) in 83% yield. Conversion of 12 into the free base and oxidation of latter with active MnO_2 in boiling CH_2Cl2 for 16 h gave 3-ethyl 3-ethyl-3H-imidazo[2,1-i]purine (13) (66% overall yield from 12), which was identical with a sample synthesized from 9-ethyladenine (9) and chloroacetaldehyde according to the general N^6,1-etheno bridgeing procedure. On treatment with methanolic ammonia at room temperature, the tricycle 15 afforded 9-ethyl-N^6-[2-(ethylamino)ethyl]adenine hydrobromide (26) in 79% yield. Mechanisms are proposed for the above intramolecular cyclizations of 1 a caused by the S- and P-atom nucleophiles.
公益社団法人日本薬学会の論文
1993-03-15