Solid-phase synthesis of functionalized 1,2,4-triazin-6-ones

Solid‐Supported Synthesis and 5‐HT7/5‐HT1A Receptor Affinity of Arylpiperazinylbutyl Derivatives of 4,5‐dihydro‐1,2,4‐triazine‐6‐(1H)‐one

“…Then, obtained support‐bound amides 9 were converted into respective thio‐analogs using Lawesson reagent in THF. Treatment of the obtained thioamides 10 with hydrazine monohydrate solution in dioxane at 90 °C for 36 h allowed for the one‐pot cleavage and cyclization which yielded the final triazinone derivatives 11 – 20 . These were purified after evaporation of the cleavage cocktail using preparative LC‐MS.…”

“…Presented work allowed for identification of some potent dual 5-HT 7 /5-HT 1A receptor ligands (13,14,(18)(19)(20). Moreover, the study revealed that LCAPs with triazinone fragment might be regarded as a new core for the development of 5-HT 7 and 5-HT 1A Rs ligands.…”

“…General procedure for cleavage/cyclization (11)(12)(13)(14)(15)(16)(17)(18)(19)(20) Solution of hydrazine monohydrate (30 eq, 2.4 mmol, 120 mg) in dioxane (1.5 mL) was added to resin-bound products 10 (125 mg each), and the reactors were placed at 90°C for 36 h. The filtrate was recovered, and the resin was washed with dioxane (3 9 1 mL). The combined fractions were subsequently evaporated under vacuum, dissolved in MeCN/H 2 O (50/50; v/v), and lyophilized to yield a white foam which was further purified using preparative liquid chromatograph coupled to mass spectrometer.…”

“…The presence of chlorine atom in the position 4 of the phenyl ring significantly decreased affinity for 5-HT 1A Rs and increased 5-HT 7 /5-HT 1A receptor selectivity (11 versus 15). Interestingly, the introduction of halogen atoms in the positions 2 and 3 of the phenyl ring (16,20) gave dual 5-HT 7 and 5-HT 1A receptors ligands with binding preference for 5-HT 7 sites.…”

Six‐Membered Heterocycles: Triazines, Tetrazines and Other Polyaza Systems

“…This synthesis has also been studied in the solid phase [263] (Scheme 20.48). Another procedure for the solid-phase synthesis of functionalized 4,5-dihydro-1,2,4-triazin-6(1H)-ones 166 has been developed from thioamide 165 and hydrazine [264,265] …”