Synthesis from amines, tert

Synthesis of thiazolidinones [PEG -RMIM]X ionic liquids have been used for rapid synthesis of a small library of amido 4-thiazolidinones from amine, aldehyde, and mercaptoacid components (Scheme 7.22) [74]. In an initial feasibility study, acid-functionalized benzaldehydes were first coupled to the [PEG -RMIM]X ionic liquids. Imines were formed by reaction of the supported aldehydes with primary amines. The reactions were run in open vessels. Optimum results were obtained by irradiating the reaction mixture with low power at 100 °C for 20 min. The imines were then condensed with mercaptoacids to give the desired thiazolidinones which were then cleaved from the ionic liquid support by amide formation. Microwave irradiation was again used in this cleavage step. The procedure entailed addition of a small amount of solid potassium tert-butoxide to a premixed mixture of the amine and supported thiazolidinone and microwave exposure for 10-20 min at 100 or 150 °G depending on the amine used. In another study, a series of one-... 

Another inventive extension of click chemistry is the concept of cUck-resins that promote solid phase supported reactions to work under nearly perfect conditions, fulfilling the requirements of click chemistry [32, 33]. This approach has enabled the assembly of a library of carboxylic arene bioisoesters, with the general formula V [34] as potential dopamine D4 receptor ligands [35]. In essence, the authors completed parallel synthesis of bioactive tert-amines V, utilizing triazolyl-methylacrylate 7 as a linker. The product was readily generated from the commercial azidomethyl substituted polystyrene 5 and propargyl acrylate 6 via Cu(I) catalyzed 1,3-dipolar cycloaddition (Scheme 15.4). 

COPE - MAMLOC - WOLFENSTEIN Olefin synthesis Olefin formalion by elimination from tert amine N-oxides... 

The synthesis of quinapril begins with formation of the AT-carboxyalkyl alanine intermediate 26 (Scheme 10.6) (Hoefle and Klutchko, 1982 Kaltenbronn et al., 1983 Klutchko et al., 1986). Displacement of ethyl-2-bromo-4-phenylbutanoate (24) by (S)-alanyl-tert-butyl ester provided the secondary amine as a diastereomeric mixture. Deprotection of this mixture allowed for the selective recrystalhzation of the undesired (/ ,S)-isomer, and isolation of the desired (6,6)-isomer 26 from the mother liquor. 

Initially, the Boc group was used for reversible a-amine protection and most side-chain functional groups were protected as benzyl derivatives, which are stable to Boc removal in HC1 or TFA. This Boc/Bzl strategy is still frequently used and is the method of choice in several laboratories. It has, however, been replaced in many laboratories by the base-labile Fmoc group, which allows weak acid deprotection of tert-butyl groups from the side chains. For short- and moderate-sized peptides both systems are effective. For protein synthesis, the relative merits have not yet been fully established. 

Nitro-l/f-p5rrazole-l-[A/, 7V-bis(tert-butoxycarbonyl)]carboxamidine (1) has been developed as a new reagent for the rapid and efficient solid and solution phase synthesis of bis(carbamate)-protected guanidines from primary and secondary amines <99TL53>. 

The synthesis of chlorocyanoketene presented here has advantages over other routes such as dehydrohalogenation of the appropriate acid chloride.5 The most obvious advantage is that the ketene is generated slowly during thermolysis. Thus, its concentration is always low. In addition, since it is generated by pyrolytic means, the presence of tert-amines and/or metals is avoided. No other method for the synthesis of chlorocyanoketene has been reported. However, we have found that it can be prepared with difficulty from chlorocyanoacetyl chloride. 

The synthesis of FQ (Fig. 20) is simple and quite economical, which renders FQ attractive for the development of an antimalarial drug intended for use in areas, concerned by malaria, that are mostly overlaying with low-income countries. FQ was obtained starting from the commercially available AQV-dimethyl-1-ferrocenylmethanamine. The ferrocenic aldehyde results from a C-C bond formation, a two-step sequence involving metallation with tert/o-butyllithium and a reaction with DMF. This step has been previously studied and the 1,2 orientation of the two substituents of the cyclopentadienyl has been unambiguously established [125], The aldehyde is converted to the corresponding oxime, which is then reduced to the primary amine. The SNat reaction between the amine and 4,7-dichloroquinoline leads to the desired FQ [121]. 

An important application of oxidation of a C-H bond adjacent to a nitrogen atom is the selective oxidation of amides. This reaction proceeds in the presence of ferf-BuOOH as the oxidant and Ru(II) salts. Thus in the example of Eq. (36), the a-tert-butylperoxy amide of the isoquinoline was obtained, which is an important synthetic intermediate for natural products [138]. This product can be conveniently reacted with a nucleophile in the presence of a Lewis add. Direct trapping of the iminium ion complex by a nudeophile was achieved in the presence of trimethylsilyl cyanide, giving a-cyanated amines as shown in Eq. (37) [45]. This ruthenium/peracid oxidation reaction provides an alternative to the Strecker reaction for the synthesis of a-amino acid derivatives since they involve the same a-cyano amine intermediates. In this way N-methyl-N-(p-methoxyphenyl) glycine could be prepared from N,N-dimethyl-p-methoxyaniline in 82% yield. 

---