Premium
Synthesis of imidazo[4,5‐ d ]pyridazine nucleosides related to inosine
Author(s) -
Dan Cook P.,
Dea Phoebe,
Robins Roland K.
Publication year - 1978
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.5570150101
Subject(s) - pyridazine , chemistry , sodium methoxide , anhydrous , medicinal chemistry , catalysis , acetyl chloride , stereochemistry , organic chemistry
Several imidazo[4,5‐ d ]pyridazine nucleosides which are structurally similar to inosine were synthesized. Anhydrous stannic chloride‐catalyzed condensation of persilylated imidazo[4,5‐ d ]‐pyridazin‐4(5 H )one (1) and imidazo[4,5‐ d ]pyridazine‐4,7(5 H ,6 H )dione ( 16 ) with 1‐ O ‐acetyl‐2,3,5‐tri‐ O ‐benzoyl‐β‐D‐ribofuranose ( 3 ) provided (after sodium methoxide deblocking) 6‐β‐D‐ribo furanosylimidazo[4,5‐ d ]pyridazin‐4(5 H )one (5) and 3,6‐di‐(β‐D‐ribofuranosyI)imidazo[4,5‐ d ]pyridazin‐4‐one ( 7 ); and 1‐(β‐D‐ribofuranosyl)imidazo[4,5‐ d ]pyridazine‐4,7(5 H ,6 H )dione ( 19 ) and 1,5 or 6‐di‐(β‐D‐ribofuranosyl)imidazo[4,5‐ d ]pyridazine‐4,7(5 H or 6 H )dione ( 21 ), respeeitvely. 4,7‐Diehloro‐1‐β‐D‐ribofuranosylimidazo[4,5‐ d ]pyridazine ( 12 ) and dimethyl 1‐β‐D‐ribofuranosylimidazole‐4,5‐dicarboxylate ( 26 ), both prepared from stannic chloride‐catalyzed ribosylations of the corresponding heterocycles, were converted in several steps to 3‐β‐D‐ribo‐furanosy limidazo[4,5‐ d ]pyridazin‐4(5 H )one ( 14 ) and nucleosidc 19 , respectively. Acid‐catalyzed isopropylidenation of mesomeric betaine 7 or nuclcoside 14 provided 3‐(2,3‐isopropylidene‐β‐D‐ribofuranosyl)imidazo[4,5‐ d ]pyrizin‐4(5 H )one ( 31 ). 1‐β‐D‐Ribofuranosylimidazo[4,5‐ d ]‐pyridazine ( 29 ) was obtained in several steps from nueleoside 12 . The structure of the nucleosides was established by the use of carbon‐13 and proton nmr.