Benzamides fluoro

Preparation of iV-((/ )-2,2-dimethyl-[l,3]dioxolan-4-ylmethoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide... 

Cis-4-amlno-5-chloro-N-[l-[3-(4-fluoro-phenoxy) propyl]-3-methoxy-4-piperidinyl]-2-methoxy-benzamide, HCl... 

The authors adapted this methodology to prepare 3,3,3-trifluoroalanine 220. Benzamide was first converted to 217 (Ar = CgHs) followed by reductive cyclization to 5-fluoro-2-phenyl-4-(trifluoromethyl)oxazole 218 (Ar = C6H5). Displacement of fluoride in 218 gave 5-ethoxy-2-phenyl-4-(trifluoromethyl)oxazole 219, which was converted to 220 with iodotrimethylsilane (Scheme 1.61). 

Small F-thiols such as the aliphatic [ F]fiuropropane-l-thiol, a PEG3-derivative ([ F]fluoro-PEG3-thiol) and an aromatic system, 4-[ F]Fluoromethyl-N-(2-mercaptoethyl) benzamide, are also useful prosthetic groups, which allow an efficient chemoselective conjugation to N-chloroacetylated peptides (Glaser et al. 2004). 

N-(4-Fluoro-o-tolyl)-N-nitrosobenzamide dissolved in coned. H2SO4, then poured into cold water N-(4-fluoro-o-tolyl)benzamide. Y 91%. I. K. Barben and H. Suschitzky, Soc. 1960, 2735. 

As previously shown, 3-fluoro sialosyl fluorides could be employed as donor substrates for TcTS. Due to the fluoro substituent and its pronounced electron-withdrawing features at the anomeric center, these derivatives show delayed reactions with acceptor structures [28]. This effect proved to be useful in determination of essential mechanistic aspects, since the intermediate enzyme substrate complex could be crystallized and studied [25, 26]. By further modification via introduction of a 9-benzamide function as in compound 24 this effect was increased. In contrast to the expected outcome the enhanced binding of this aromatic residue was unexpectedly due to its location in the acceptor-binding site rather than in the glycerol sidechain binding domain, as evidenced by X-ray structural studies (Fig. 11) [52]. 

The application of fluorinated furazan is rather limited for synthesis and reactivity. Most studied derivative is 3-amino-4-trifluoromethyl-l,2,5-oxadiazole, which is commercially available. Nevertheless, in recent years, some perspective applications have been envisaged. In the agrochemical field a large library (more than 300 derivatives) of A-(4-triflnoromethyl-l,2,5-oxadiazol-3-yl)benzamides 257 has been prepared and considered for herbicidal activity [ 140], while l-(4-fluoro-1,2,5-oxadiazol-3-yl)pyrazole derivatives 258 were claimed as herbicides and plant growth regulators (Fig. 14) [141]. 

Fig. 2.12 Identical molecular chain formed via C-H- - -F-C H-bonds in case of a 2-fluoro-7V-(2-fluorophenyl)benzamide b 2-fluoro-iV-(2-clilorophenyl)benzaniide. c Part of crystal packing in 2-fluoio-lV-(2-bromophenyl)benzamide showing presence of C-H---F-C H-bonds [88, 89]...

Fig. 2.14 Different molecular motifs formed via C-H - F-C hydrogen bonds in the presence of strong N-H - 0=C and weak C-H-"0=C hydrogen bonds in a Af-(3-fluorophenyl)acetamide, b 3-fluoro-Af-methylbenzamide, c Af-(3-(trifluoromeihyl)phenyl)acetamide, and d Af-methyl-3-(trifluo-romethyl)benzamide [101]...

Mocilac P, Donnelly K, Gallagher JF (2012) Structural systematics and conformational analyses of a 3x3 isomer grid of fluoro-N-(pyridyl)benzamides physicochemical correlations, polymorphism and isomorphous relationships. Acta Cryst B68 189... 

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