Studies on syntheses and reactions of methoxypyridazines. I Methoxylation of 3,4,5-trichloropyridazine.

Nagashima, Hiromu; Oda, Hirohisa; Hida, J.; Kaji, Koichi

doi:10.1248/cpb.35.421

Cited by 7 publications

(4 citation statements)

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“…We therefore carried on the reaction of compound 5 with phosphorus oxychloride to obtain 3,4,5-trichloropyridazine 8 (route c), followed by stepby-step methoxylations. 12 Monomethoxylation of compound 8 with equimolar sodium methoxide at room temperature afforded a mixture of 4-methoxy-and 5-methoxy-monosubstituted derivatives 9 and 10 at 32% and 53% respectively and a tiny amount of the 3-methoxy analogue, which is in agreement with previously reported data. 12 The monomethoxy compounds 9 and 10 were further methoxylated with an equimolar amount of NaOMe under reflux conditions to give the dimethoxy compounds 11 (minor) and 12 (major), 12 (minor) and 13 (major), respectively.…”

Section: Synthesissupporting

confidence: 91%

“…12 Monomethoxylation of compound 8 with equimolar sodium methoxide at room temperature afforded a mixture of 4-methoxy-and 5-methoxy-monosubstituted derivatives 9 and 10 at 32% and 53% respectively and a tiny amount of the 3-methoxy analogue, which is in agreement with previously reported data. 12 The monomethoxy compounds 9 and 10 were further methoxylated with an equimolar amount of NaOMe under reflux conditions to give the dimethoxy compounds 11 (minor) and 12 (major), 12 (minor) and 13 (major), respectively. On the basis of the above results, we can conclude that the reactivity of the three chlorine atoms of the multichloropyridazines is 5 > 4 > 3.…”

Section: Synthesissupporting

confidence: 91%

“…5-Chloro-3,4-dimethoxypyridazine (11) and 3-chloro-4,5-dimethoxypyridazine (12). Monomethoxylated product 9 (3.62 g, 20 mmol) in MeOH (40 ml) was added NaOMe (25% in MeOH, 20 mmol, 1 equiv.)…”

Section: General Proceduresmentioning

confidence: 99%

“…1 H NMR (CDCl 3 ) for 9: δ 9.01 (s, 1H), 4.15 (s, 3H); 1 H NMR (CDCl 3 ) for 10: δ 8.91 (s, 1H), 4.13 (s, 3H). 5-Chloro-3,4-dimethoxypyridazine ( 11) and 3-chloro-4,5dimethoxypyridazine (12). Monomethoxylated product 9 (3.62 g, 20 mmol) in MeOH (40 ml) was added NaOMe (25% in MeOH, 20 mmol, 1 equiv.)…”

Section: General Proceduresmentioning

confidence: 99%

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Synthesis and characterizations of pyridazine-based iron chelators

Kong

Chen

et al. 2014

Dalton Trans.

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In an attempt to design ligands which require both a high iron(III) affinity and a low iron(II) affinity, the 3-hydroxypyridin-4-one structure has been modified to introduce an additional nitrogen atom in the pyridine ring to form a pyridazine. The target molecules were synthesized from a chlorine-substituted pyridazine using step-by-step methoxylations. A total of six 3- and 5-hydroxypyridazin-4(1H)-ones have been synthesized, with a methyl, ethyl or n-propyl group on the N1 of the pyridazine ring. In the reaction of the pyridazines with alkyl iodide, the presence of acetone drives the reaction to afford pyridazinones rather than the desired pyridaziniums. The pK(a) values of the free ligands, the stability constants of their iron(III) complexes and corresponding pFe(III) values demonstrate that this type of ligand has lower values when compared with those of deferiprone. The reduction potential values of the iron complexes obtained from cyclic voltammetry measurements, are used to determine the corresponding pFe(II) values. Although two compounds of the 20 series have marginally higher log β3(Fe(III))/log β3(Fe(II)) ratios than those of deferiprone, they possess pFe(III) values <20, indicating that this type of chelator is unlikely to be optimized into a useful therapeutic agent.

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Section: Synthesissupporting

confidence: 91%

Section: Synthesissupporting

confidence: 91%

Section: General Proceduresmentioning

confidence: 99%

Section: General Proceduresmentioning

confidence: 99%

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