Preparation of a series of 5-methyl-3-(substituted)-[1,2,4]triazines

Gichinga, Moses G.; Olson, Jeremy P.; Butala, Elizabeth; Gilmour, Brian P.; Navarro, Hernan; Carroll, F. Ivy

doi:10.1016/j.tetlet.2011.04.075

Cited by 2 publications

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“…Although a modest yield of 29 % was obtained when n ‐propanol was used to synthesize 3‐( n ‐propoxy)‐1,2,4‐triazine ( 13a ; Table , Entry 2), the yields considerably improved when more acidic alcohols (Table , Entries 3 and 4) and phenols (Table , Entries 5–7) were used as the nucleophilies , . Notably, the employment of Cs 2 CO 3 as a mild and efficient base in the reaction of phenols with 5a is more desirable than using a strong, moisture‐sensitive base such as NaH, which is the preference of the literature procedure , . In contrast, when a weaker base such as Na 2 CO 3 was used for the reaction of 5a with n ‐propanol, we did not observe any formation of 13a (Table , Entry 1).…”

Section: Resultsmentioning

confidence: 76%

“…Although the reactivities of compounds that contain the core structure 5 have been explored with mercaptans, alcohols, and amines, these reactions are carried out under a variety of conditions that can differ significantly with regards to the strength of the base. For example, some reports describe the use of milder bases such as lutidine or triethylamine for the reaction of 5 with mercaptans,, whereas others use much harsher conditions such as employing NaH as the base for the reaction . Similarly, the reactions of alcohols with 5 have been carried out with a stronger base, including BuLi according to some reports , .…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of 3‐(Alkylamino)‐, 3‐(Alkoxy)‐, 3‐(Aryloxy)‐, 3‐(Alkylthio)‐, and 3‐(Arylthio)‐1,2,4‐triazines by Using a Unified Route with 3‐(Methylsulfonyl)‐1,2,4‐triazine

et al. 2016

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Synthesis of 3-(Alkylamino)-, 3-(Alkoxy)-, 3-(Aryloxy)-, 3-(Alkylthio)-, and 3-(Arylthio)-1,2,4-triazines by Using a Unified Route with 3-(Methylsulfonyl)-1,2,4-triazineDa-Hua Shi, [a] Jitendra R. Harjani,* [a] Robert W. Gable, [b] and Jonathan B. Baell* [a] Abstract: In our attempts to synthesize 3-(alkylthio)-and 3-(alkoxy)-1,2,4-triazines without substituents at the 5-or 6-position, the synthesis of their anticipated precursor 3-(methylsulfonyl)-1,2,4 triazine was also optimized. The reactivity of 3-(methylsulfonyl)-1,2,4-triazine towards alkyl and aryl thiols, primary and secondary alkylamines, phenols, and alcohols was explored, and the reactions were optimized to maximize the isolaIntroduction 3-Substituted 1,2,4-triazines 1 (Figure 1) have been used as precursors in the syntheses of furo-, dihydrofuro-, thieno-, thiopyrano-, pyrrolo-, and dihydropyrano [2,3-b]pyridines by intramolecular Diels-Alder reactions. [1][2][3] A number of these heterocyclic cores are found in antibiotics and herbicides that have pharmacological activity. [1][2][3] In the context of medicinal chemistry, 3-substituted 1,2,4-triazines 1 have drawn attention as mGluR5 antagonists, which are targets in the development of pharmacotherapies to treat drug and alcohol addictions. [4][5][6] Some 3-substituted 1,2,4-triazines have been found to inhibit SCD-1, an enzyme linked to obesity and hepatocarcinogenesis, [7] whereas others have been identified as selective serotonin 5-HT 7 ligands.[8] A very recent report describes their potential as compounds that are capable of modulating skeletal muscle contractility.[9] Our group has identified some 3,3′-disubstituted 5,5′-bi-1,2,4-triazines, which are conveniently derived from 3-substituted 1,2,4-triazines by a cyanide-induced oxidative coupling reaction (Scheme 1) and have low nanomolar levels of activity against Plasmodium falciparum with low cytotoxicity. [10] A literature survey of 3-substituted 1,2,4-triazines indicates that 3-halo-, 3-methylthio-, and 3-methylsulfonyl-1,2,4-triazines (i.e., 2-5) are the most frequently employed precursors for their synthesis (Figure 1). As described in a recent report, the substitution of a bromo group at the 3-position of 1,2,4-triazines with [ tion of the corresponding 3-substituted 1,2,4-triazine. Good yields were obtained for the products of the reactions with all of the aforementioned nucleophiles, with the exception of alcohols, by using alkali metal carbonates. Higher yields of 3-(alkoxy)-1,2,4-triazines were obtained by using the appropriate magnesium alkoxide as the nucleophile.

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Section: Resultsmentioning

confidence: 76%