Amino amides, preparation

A series of imidazolidin-4-ones 117 were prepared from a-amino amides 116 that reacted with aldehydes without solvent at 200 °C imder microwave irradi-... 

Diarylimidazohnes 119 that act as potential P2X receptor antagonists have been prepared by microwave-assisted cyclization of amino amides in the presence of TMS-polyphosphate at 140 °C for 8 min [78]. This reaction seems quite general (for variations on R) as more than 35 compounds have been prepared with this method (Scheme 41). 

A particularly interesting application of this reagent is the preparation of "geminal amino amides," a novel class of compounds that have surprising... 

In summary, the direct insertion of zinc dust to organic halides is an excellent method for preparing a broad range of polyfunctional organozinc halides bearing various functional groups like an ester" , an ether, an acetate" , a ketone, cyano", halide" , N,N-bis(trimethylsilyl)amino °, primary and secondary amino, amide, phthalimide , sulfide, sulfoxide and sulfone , boronic ester , enone " or a phosphonate . An alternative method is based on transmetalation reactions. 

The required a,a-disubstituted amino acid for 18 was prepared by an enzymatic resolution of the corresponding racemic amino amide (Scheme 28.11) (see also Chapters 2 and 19).42... 

Both Siegel et al. (122) and Lawrence et al. (123) have described automated systems for the purification of small arrays of amines and amides. A 48-member array of P-amino alcohols prepared from epoxides and amines was purified using SPE by Shuker et al. (124). Blackburn et al. (125) have described the purification of a 60-member 3-aminoimidazo[l,2-fl]pyridine array obtained from a multiple-component condensation, and Bussolari et al. (126) purified a small array of phenylpropyl amines obtained from dihydrocoumarins and amines. A few applications where ion-exchange resins have been substituted with other solid phases have also recently appeared. For example, the purification of several carbohydrate arrays tagged as hydrophobic O-laurates using Ci8 silica producing up to 10-30 mg of >90% pure individuals was described by Nilsson et al. (127), and Curran et al. purified fluorous-... 

The Hofmann and Curtius reactions as applied to both the mono-and diamides and hydrazides have been reported. Marquardt found that a low yield of the amine can be obtained in the Hofmann reaction of l,2,5-thiadiazole-3-carboxamide. The main side reaction was hydrolysis of the electron-deficient amide to the carboxylic acid. Under the same conditions the dicarboxamide (78) formed the amino acid (16b). Attempts to prepare diaminothiadiazole via the Hofmann reaction of the amino amide (16a) resulted only in amide hydrolysis and the formation of the same amino acid. 

Very often reduction of an aromatic nitro compound is carried out in the presence of acetic anhydride, whereby the corresponding acetamido compound is formed. Amino amides are prepared by catalytic hydrogenation of nitro amides, e.g., 2-aminoacetanilide (90%). ... 

In addition to the acetate aldol problem, stereoselective aldol additions of substituted enolates to yield 1,2-anti- or f/treo-selective adducts has remained as a persistent gap in asymmetric aldol methodology. A number of innovative solutions have been documented recently that provide ready access to such products. The different successful approaches to anri-selective propionate aldol adducts stem from the design of novel auxiliaries coupled to the study of metal and base effects on the reaction stereochemistry. The newest class of auxiliaries are derived from A-arylsulfonyl amides prepared from readily available optically active vicinal amino alcohols, such as cw-l-aminoindan-2-ol and norephedrine. 

Esters, Carboxylic Acids, and Ethers.—The rates of hydrolysis of 3(3- and 6(3-acetoxy-4 ,5 -epoxides and 1 a-acetoxy-2(3,3 (3-epoxides were observed to be accelerated relative to those acetates not containing a neighbouring epoxide group.24 Bile acid methyl esters were readily prepared from the carboxylic acids by reaction with methanol in the presence of toluene-p-sulphonic acid.25 Bile acids were readily converted into the amino-amides (14) by successive reaction with Bu N-... 

Although initially prepared and evaluated as a racemate, the NMDA antagonist activity was likely to reside primarily in a single enantiomer. The stereoselective nature of the NDMA receptor is well established, albeit not completely understood. Consequently, several attempts have been undertaken to develop synthetic protocols that would allow preparation of optically active compounds. Early reports of preparation of optically active co-amino-o-carboxyalkylphosphonic acids describe the preparation of (.S )-A P-3 from an optically active amino nitrile prepared by reaction of diethyl 1-formylphosphonate with hydrogen cyanide and (5)-(-)-a-methylbenzylamine. Acid hydrolysis, enrichment of the diastereomers by fractional recrystaUization, and debenzylation lead to the isolation of (.S )-A P-3 in 86% enantiomeric excess. " Recently reported procedures, which use chemoenzymatic processes, offer a more convenient and mild approach for the production of optically pure aminophosphonic acids. Enzymatic hydrolysis of amides using penicillinacylase (EC... 

Linear polyamide resins are prepared by the reaction of dimer fatty acid and diamine compounds. The resulting resin has frequent inner molecular ring structures and a repeating amino amide structure. 

The Swem oxidation of A-Fmoc-protected -amino alcohols 8 (Scheme 4) and the reduction of Weinreb amides prepared from Fmoc-a-amino acids with LiAlH4 at — 78°C were compared [83]. Both approaches afforded comparable synthetic yields, typically between 70 and 90% of the... 

In contrast, allergic reactions to local anesthetics, although rare, are known to occur exclusively with p-aminobenzoic ester-type local anesthetics (18). Whether the formation of PABA on ester hydrolysis is solely responsible for this hypersensitivity remains to be investigated. However, the preservative compounds, such as methyparaben, used in the preparation of amide-type local anesthetics are metabolized to PABA-like substance, p-hydroxybenzoic acid. Thus, patients who are allergic to amino ester-type local anesthetics should be treated with a preservative-free amino amide-type local anesthetic. 

---