1-Poly(fluoroalkyl)benzodiazepines

The first example of linear peptides containing a N-trifluoroethylated backbone amide linkage and the surprising solution dynamics observed by 19F NMR

“…In the early 1970s, Steinman et al [2] prepared 1-trifluoroethyl-5-phenyl-1,4-benzodiazepin-2-one (II in Scheme 1) in low yields by first removing proton from 1 position of parent compound (I) and then reacting with trifluoroethyl iodide. This reaction could not be substantially improved by altering the reaction conditions or by the use of trifluoroethyl benzenesulfonate or trifluoroethyl trichloromethanesulfonate (triclate) as the alkylating agents.…”

“…Based on Dickey's research [12], trifluoroethylation of anilines with 2-chloro-1,1,1-trifluoroethane by autoclave reactions, and Hansen's work [13], trifluoroethylation of diethylamine with trifluoroethyl trifluoromethanesulfonate (triflate), Steinman et al [2] prepared and used triclate to obtain the secondary Ntrifluoroethylated anilines and aminobenzophenones. These were then coupled directly with bromoacetyl bromide and phthalimidoacetyl chloride to form desired tertiary amide functionalities.…”

“…Selective trifluoroethylation of bioactive compounds has been investigated since the early 1960s [1][2][3][4][5]. However, the progress in this research area is much slower compared to selective fluorination of bioactive compounds, such as amino acids and peptides [6,7].…”

“…However, the progress in this research area is much slower compared to selective fluorination of bioactive compounds, such as amino acids and peptides [6,7]. In the past decade, we have focused on the synthesis and applications of the novel trifluoroethylating agent CF 3 CH 2 I(C 6 H 5 )N(SO 2 CF 3 ) 2 . The chemo selectivity of this agent was demonstrated by trifluoroethylation of the functionalities of a-amino acids [8][9][10].…”

[2′‐18F]‐2‐oxoquazepam: Synthesis of a 5‐(2‐[18F]fluorophenyl)‐1,4‐benzodiazepine‐2‐one

“…A major chemical component which might be expected to cause separation problem would be any amounts of the 2'-nitro-l,4-benzodiazepin-2-one co-synthesized, by the same reactions as for 5, from the 2-nitrobenzaldehyde used in the synthesis of 2. We were, however, unsuccessful in synthesizing reference 2'-nitro-1,4-benzodiazepin-2-one by this method nor has it, to our knowledge, been reported in the literature, 1,4-Benzodiazepine-2-ones with nitro groups in the 5-aryl ring have been prepared by direct nitration, with substitution occurring primarily in the meta position (19). On the straight-phase system used for the preparative separation (18) it was found that a relationship between the capacity factor, k', and the om values could be used to predict the relative retention times for the benzodiazepines.…”