Benzamide derivatives

When the benzamide derivative of 3-picoline 17 was subjected to the cyclization conditions with -BuLi, the reaction failed to yield the desired indole 18. However, when -BuLi was replaced by LDA, the desired azaindole 18 was isolated in 22% yield." ... 

It has been shown that, in the presence of lithium diethylamide at —70 °C, bromoben-zoic acids form arynes which may react with arylacetonitriles to yield, predominantly, 2-cyanobenzoic acids. The reaction of alkyl and aryl isocyanides with benzyne may yield benzamide derivatives, showing their ability to act as charge-reversed equivalents to isocyanates. The generation and cyclization of a benzyne-tethered alkyllithium have been reported, and lead to a convenient synthetic route for 4-substituted indans. ... 

Suzuki, T., Ando, T., Tsuchiya, K., Fukazawa, N., Saito, A., Mariko, Y. et al. (1999) Synthesis and histone deacetylase inhibitory activity of new benzamide derivatives. Journal of Medicinal Chemistry, 42, 3001-3003. 

The iodo benzamide derivative of pyrrolo[2,l-c][l,4]benzodiazepine 367 (R = I, Scheme 75, Section 5.1.1) reacts with bis(tributyl)tin, lithium chloride and tetrakis(triphenylphosphine) palladium(O) in refluxing dioxane to yield the stannyl derivative 370. The latter couples with substituted aryl bromides in the presence of... 

Rhodium-catalyzed hydroformylation of -(substituted amino)benzyl-amines (387, X = H2) and -(substituted amino)benzamides (387, R = H, X = O) in the presence of rhodium(II) acetate dimer and triphenylphos-phine in deoxygenated ethyl acetate gave a 7 3 mixture of 1,2,3,4,4 ,5-hexahydro-6//-pyrido[l,2-a]quinazolines (388, X = H2,0) and isomeric 3-methyl-l,2,3,3fl,4,5-hexahydropyrrolo[l,2-a]quinazolines (389, X = H2, O) (94AJC1061). The methyl derivative of benzylamine 387 (R = Me, X = H2) afforded a mixture of diastereoisomers 390 and 391 (X = H2). Their ratio depended on the reaction time. Longer reaction times gave more 391 (X = H2), containing the methyl group in an equatorial position. Compound 390 isomerized into 391 (X = H2), under the aforementioned conditions. The benzamide derivative (387, R = Me, X = O) yielded only one isomer (391, X = O), independent of the reaction period. 

Bockaert J, Sebben M, Dumuis A. Pharmacological characterization of 5-hydroxytryptamine4 (5-HT4) receptors positively coupled to adenylate cyclase in adult guinea pig hippocampal membranes effect of substituted benzamide derivatives. Mol Pharmacol 1990 37 408-411. 

The example of amisulpride (launched by Sanofi-Synthelabo in 1986) also supports the primary importance of dopamine D2 (as well as D3) but not 5-HT2A receptors in atypical antipsychotic action. This benzamide derivative displays high affinity only to D2 and D3 receptors (with some selectivity toward D3) [42], and in low doses (i.e., 50-100 mg day-1) it acts preferentially on negative [43] symptoms and at higher doses (400-800 mg day-1) on depressive symptoms [44] and cognitive impairment [45]. 

Trifluoromethyl benzamide derivatives, (VI), prepared by Chemey were effective as MCP-1 modulators and useful in treating inflammation disorders such as rheumatoid arthritis, asthma, and restinosis. 

Ultrarapidly activating potassium Kvl.5 channel blockers consisting of benzamide derivatives, (II), prepared by Baker (4) were effective in treating atrial fibrillation disorders. 

Phenyl-alkylene benzamide derivatives, (IV), effective as orexin antagonists were useful in the treatment of growth hormone deficiency associated with hypothalamic disorders. 

Water is used to remove excess sulfuric acid, and ethyl acetate to remove triphenylmethanol, benzophenone and the N-benzamide derivative of proline. 

The pK, of the protonated (CONH2)4 radical is 2.0, with a shift from 425 nm to 400 nm on deprotonarion. The change in the absorption maxima for both 3- and 4-carbamidopyridinyl radicals implies protonation on the amide group rather than the ring (Eq. 26). Thus, the pyridinyl radicals are more basic than benzamide derivatives, but very weakly basic compared to dihydropyridines (pK, ca. 7) or typical tertiary amin (pK, ca. 10-11). 

Within A -Phth-protected amino acid derivatives the C—N bond is extremely susceptible to basic and nucleophilic conditions, thus, leading to unwanted base-catalyzed side reactions of the Phth derivatives in the course of synthetic steps. The applicability of the phthalimido chemistry has been extended by converting the phthalimido moiety into the corresponding 2-(pyrrolidinocarbonyl)benzamide derivative 81, thereby eliminating the base- and nucleophile-sensitivity of the parent phthaloyl derivative (Scheme... 

After converting A -Phth-protected amines into the corresponding 2-(pyrrolidinocarbon-yl)benzamide derivative, Dieckmann reactions, ester hydrolysis, and transesterfication can be carried out. This strategy of pyrrolidine-based deactivation of phthaloyl-protected anoines followed by reclosure of the phthaloyl group has successfully been applied in the synthesis of (3-lactam antibiotics.P l... 

There are interesting transition metal-catalyzed-reactions that lead to aryl amides. The use of POCI3 and DMF, with a palladium catalyst, converts aryl iodides to benzamides. A palladium-catalyzed reaction of aryl hahdes and for-mamide leads to benzamide derivatives. Carbonylation is another method that generates amides. When an aryl iodide was treated with a secondary amine and Mo(CO)e, in the presence of 3 equivalents of DBU, 10% Pd(OAc)2, with micro-wave irradiation at 100°C, the corresponding benzamide was obtained. 

From the initial compounds it was clear that the spacing between the amide and the aromatic ring system in the N-methylamide side chain is critical for K-receptor activity. Whereas phenylacetamide derivatives (i.e., -NCHgCOCHaAr) such as U50,488 and its analogs exhibit k activity, benzamide derivatives (i.e., NHCOAr and -NCHgCOAr) exhibit morphine-like effects (115,488). In both series N-methyl substitution increases potency over the unsubstituted secondary amides (115, 489). 

Anionic bridged bis(amidinate) lithium lanthanide complexes have been found to be efficient catalysts for the amidahon of aldehydes with amines under mild conditions (Scheme 56). The achvity was found to follow the order of yttrium < neodymium < europium ytterbium. The catalysts are available for the formahon of benzamides derived from pyrrolidine, piperidine, and morpholine with good to excellent yields. In comparison with the corresponding neutral complexes, the anionic complexes showed higher achvity and a wider range of scope for the amines. A cooperation of the lanthanide and lithium metals in this process was proposed to contribute to the high activity of these catalysts [66,67]. 

Cyclization of 2,2 -Dithiobis(Benzaldehyde) and-(Benzamide) Derivatives via Sulfenylhalides... 

Suzuki T et al (1999) Synthesis and histone deacetylase inhibitory activity of new benzamide derivatives. J Med Chem 42(15) 3001-3003... 

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