Palladium catalyzed amination of 2-chloro-1,3-azole derivatives: Mild entry to potent H1- antihistaminic norastemizole

Hong, Yaping; Tanoury, Gerald J.; Wilkinson, H. Scott; Bakale, Roger P.; Wald, Stephen A.; Senanayake, Chris H.

doi:10.1016/s0040-4039(97)01273-2

Cited by 64 publications

(43 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[19] Lately, the palladium-catalyzed amination of 2-chlorobenzimidazoles, based on Buchwald chemistry, has also been described. [20,21] Despite recent advances towards a more direct synthesis of 2-aminobenzimidazoles, the synthetic approach in Janssen's seminal article [22] was preferred for our work because it does not use expensive catalysts, microwave irradiation, or high temperatures leading to undesired byproducts.…”

Section: Synthesismentioning

confidence: 99%

Synthesis and Anti‐Plasmodium Activity of Benzimidazole Analogues Structurally Related to Astemizole

2013

View full text Add to dashboard Cite

A series of compounds structurally related to astemizole were designed and synthesized with the goal of determining their anti-Plasmodium activity. Several modifications of the astemizole structure, namely the removal of the 4-fluorobenzyl and/or 4-methoxyphenethyl moieties, substitution of the benzene ring of the benzimidazole scaffold, replacement of the fluorine atom in the 4-fluorobenzyl group, and variation of the 4-aminopiperidine moiety, were explored. In vitro evaluation of the anti-Plasmodium activity of these compounds using the ItG strain showed that astemizole and some of its structurally similar derivatives have IC50 values in the nanomolar range and exhibit toxicity towards the parasite over Chinese ovarian hamster (CHO) cells with a selectivity as high as 200. The presence of a secondary cyclic amine at position 2 and substitution with chlorine at positions 4 and 5 in the benzimidazole moiety are two modifications that resulted in potent and selective antimalarials based on astemizole.

show abstract

Section: Synthesismentioning

confidence: 99%

Synthesis and Anti‐Plasmodium Activity of Benzimidazole Analogues Structurally Related to Astemizole

2013

View full text Add to dashboard Cite

show abstract

“…This procedure has been successfully applied mainly to benzo or hetero fused imidazole derivatives. Thus, the reaction of 2-chlorobenzimidazoles with 4-aminopiperidine led to the preparation of the antihistaminic norastemizole, 45 while a series of amide substituted purine derivatives were synthesized via palladium-catalyzed amidation reactions. 46 Thus, we set out to search for an adequate catalytic system to achieve the C-N coupling between p-anisidine and 2-bromo-1-methylimidazole (9) (Scheme 3).…”

Section: Scheme 2 Issue In Honor Of Prof Rosa M a Claramunt Arkivoc mentioning

confidence: 99%

C-N bond forming reactions in the synthesis of substituted 2-aminoimidazole derivatives

Gómez-SanJuan¹,

Botija²,

Méndez³

et al. 2013

Arkivoc

View full text Add to dashboard Cite

Carbon-nitrogen bond forming reactions oriented to the synthesis of 2-amino-imidazolidines and imidazoles have been investigated. The C-2 amination of imidazolidinones, via the corresponding 2-chlorodihydroimidazoles, led to 2-benzylaminodihydroimidazole or bis(dihydroimidazole)amino derivatives by choosing the adequate experimental conditions. On the other hand, the use of N-acyl-2-methylsulfanyldihydroimidazoles allowed carrying out the reactions with aromatic amines, such as p-anisidine. Finally, palladium catalyzed BuchwaldHartwig amination was the method of choice for C-N coupling between 2-haloimidazoles and aromatic amines in the synthesis of the corresponding imidazoles.

show abstract

“…For example, the reaction of primary amines with chloro-1,3-azoles has been used to produce the H-1-antihistaminic norastemizole [200]. As shown in Eq.…”

Section: Arylation Of Primary Alkylaminesmentioning

confidence: 99%

Palladium‐Catalyzed Amination of Aryl Halides and Sulfonates

Hartwig

2002

Modern Arene Chemistry

View full text Add to dashboard Cite

The transition metal catalyzed synthesis of arylamines by the reaction of aryl halides or triflates with primary or secondary amines has become a valuable synthetic tool for many applications. This process forms monoalkyl or dialkyl anilines, mixed diarylamines or mixed triarylamines, as well as N-arylimines, carbamates, hydrazones, amides, and tosylamides. The mechanism of the process involves several new organometallic reactions. For example, the CaN bond is formed by reductive elimination of amine, and the metal amido complexes that undergo reductive elimination are formed in the catalytic cycle in some cases by NaH activation. Side products are formed by b-hydrogen elimination from amides, examples of which have recently been observed directly. An overview that covers the development of synthetic methods to form arylamines by this palladium-catalyzed chemistry is presented. In addition to the synthetic information, a description of the pertinent mechanistic data on the overall catalytic cycle, on each elementary reaction that comprises the catalytic cycle, and on competing side reactions is presented. The review covers manuscripts that appeared in press before June 1, 2001. This chapter is based on a review covering the literature up to September 1, 1999. However, roughly one-hundred papers on this topic have appeared since that time, requiring an updated review.

show abstract

Palladium catalyzed amination of 2-chloro-1,3-azole derivatives: Mild entry to potent H1- antihistaminic norastemizole

Cited by 64 publications

References 18 publications

Synthesis and Anti‐Plasmodium Activity of Benzimidazole Analogues Structurally Related to Astemizole

Synthesis and Anti‐Plasmodium Activity of Benzimidazole Analogues Structurally Related to Astemizole

C-N bond forming reactions in the synthesis of substituted 2-aminoimidazole derivatives

Palladium‐Catalyzed Amination of Aryl Halides and Sulfonates

Contact Info

Product

Resources

About