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Synthesis and NMR studies of some imidazo[4,5‐ d ]pyridazine nucleosides
Author(s) -
Gagnier R. Paul,
Halat Michael J.,
Otter Brian A.
Publication year - 1984
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570210243
Subject(s) - chemistry , pyridazine , nucleoside , boron trichloride , ribonucleoside , stereochemistry , nuclear magnetic resonance spectroscopy , derivative (finance) , medicinal chemistry , computational chemistry , boron , organic chemistry , rna , biochemistry , financial economics , economics , gene
Unlike imidazo[4,5‐ d ]pyridazin‐4(5 H )‐one ( 1a ), which undergoes ribosylation at N‐6 in the Vorbruggen procedure for nucleoside synthesis, the 5‐benzyloxymethyl derivative 12 undergoes ribosylation at N‐1 and N‐3 to give a separable mixture of 14 and 15 . Removal of the N‐5 blocking groups from 14 and 15 by treatment with boron trichloride at −78° affords the intermediates 16 and 17 , which were debenzoylated to give the 4‐oxo nucleosides 5 and 6 . Thiation of 16 and 17 , followed by S‐methylation and ammonolysis leads to the 4‐amino nucleosides 2 and 3 . The glycosylation sites of these nucleosides were assigned by using a combination of 1 H and 13 C nmr data, especially measurements of the spin‐lattice relaxation times (T 1 ) of the base protons. Using these techniques, it is shown that a nucleoside previously reported to be 3 is in fact the N‐6 isomer.