4(And 5)‐cyclopropylamino‐5(and 4)halo‐3(2H)pyridazinones. Formation and characterization of isomers

Abstract

The reactions of 4,5‐dihalo‐3(2H)pyridazinones with ammonia and amines gave mixtures of 5‐amino‐4‐halo‐ and 4‐amino‐5‐halo‐3(2H)pyridazinones separated by chromatography. Structures were elucidated by means of retention values (Rf) and confirmed by independent synthesis.

A Concise Synthesis of a Tetrahydropyrazolopyrazine Building Block

“…Compound 8 was prepared in three steps and 77% yield from 3,6-dichloropyridazine using an optimized process based on literature procedures. 8,13 5-Methyl-2-nitro-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (11). 2-Methylaminoethanol (220 g, 2.92 mol), toluene (2.68 L) and 1 (383 g, 2.47 mol) were cooled to 15 °C, then thionyl chloride (498 mL, 6.83 mol) was added over 10 min at ≤25 °C, followed by DMF (18.8 mL).…”

“…As a variety of closely related compounds have also been prepared using essentially the same method according to the patent literature, − ,, a more robust method preferably without using a transition metal would be highly desirable. Alkylamines have been reported to directly react with analogues of 8 . − In addition, the coupling of a less reactive arylamine with 8 using potassium tert- butoxide as the base has been reported, albeit to give the desired product in low yield of 25%…”

Suzuki-aza-Wittig, Suzuki-condensation and aza-Wittig-electrocyclic ring-closure tandem reactions for synthesis of fused nitrogen-containing ring systems

“…19 Compound 1d was obtained similarly, while the literature described its synthesis by the reaction of the 2-methyldichloro compound 1c with concentrated HI. 20 Regioselective amination of 4,5-dibromo-2-methylpyridazin-3(2H)-one 1b, 21 and 2-benzyl-4,5-dibromopyridazin-3(2H)-one 1a 22 could not be achieved by reaction with aqueous ammonia to the appropriate 5-amino-4-bromo derivatives 5a 23 and 5b 21 as the isomeric 4-amino-5-bromo compounds 6a and 6b 21 were also formed in minor amounts. The same problem was encountered in the case of the published 15,16 reactions of 4,5-dichloro-2-methylpyridazin-3(2H)-one 1c 17 with different amines.…”

Synthesis and Biological Evaluation of Novel Pyridazinone-Based α4Integrin Receptor Antagonists

“…4-Halopyridazinone precursors were commercially available or were prepared using published procedures. , In cases where preparation of the required halopyridazinone has not been reported, experimental methods are provided preceding the synthesis in which it was used.…”