A-carboxamide

This compound was first isolated as a secondary reaction product in the formation of diaminoguanidine hydrobromide and guanazine from the reaction of cyanogen bromide 

The reaction is carried out in a 2-1. beaker above which is suspended a 500-ml. dropping funnel for slow addition of the cyanate solution. A mechanical stirrer is employed to agitate the mixture throughout the reaction and digestion processes. 

Ninety-nine grams of carbohydrazide (1.10 mols) is dissolved in a solution containing 120 g. of glacial acetic acid (2.00 mols) and 1000 ml. of water. To this, a solution of 81 g. of potassium cyanate (1.00 mol) in 350 ml. water is added dropwise over a period of about 2 hours. The mixture is digested at room temperature for 5 hours. The precipitate is then removed by filtration and washed very thoroughly with water, alcohol, and ether. The dry product weighs approximately 115 g. (86%) and melts with decomposition at 227 to 228°. 

Carbohydrazide-iV-carboxamide is a white, nonhygro-scopic, crystalline substance which is insoluble in water and in alcohol and other organic solvents. It is soluble in mineral-acid solutions, from which it may be reprecipitated by the addition of ammonia however, it dissolves in sodium hydroxide with decomposition. 

This compound reduces Fehling solution and ammo-niacal silver nitrate readily. It is quite stable for long periods of time at 110°. When heated for 1 hour at 226°, it cyclizes to form urazine (synthesis 9). It condenses with aldehydes and ketones the hydrochloride reacts with addi- 

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A side chain carboxyl group in perhydropyrido[l,2-a]pyrazines was obtained from an ester group by acidic or alkalic hydrolysis. A side chain carboxyl group was converted into a carboxamide group by the treatment with an amine in the presence of 1-hydroxybenzotriazole (OOJAP(K)OO/ 86659). 

Further SAR studies on the cyclopentane scaffold have included variation of the hydrophobic side-chain to incorporate a carboxamide substituent (Chand et al. 2004), equivalent to the C6-carboxamide derivatives of zanamivir, and extension of the length of the hydrophobic side-chains (Chand et al. 2005a). Analogues that incorporate a longer 4-heptyl side-chain showed comparable efficacy to 34 upon oral and intranasal administration in mice, and comparable or better efficacy than oseltamivir and zanamivir (Chand et al. 2005a). 

The amino acid sequence of our first aPNA (which we termed backbone 1 or bl) was designed based on this amphipathic hehx sequence (Fig. 5.3 B). Specifically, this aPNA backbone included hydrophobic amino acids (Ala and Aib), internal salt bridges (Glu-(aa)3-Lys-(aa)3-Glu), a macrodipole (Asp-(aa)i5-Lys), and an N-ace-tyl cap to favor a-helix formation. The C-termini of these aPNA modules end in a carboxamide function to preclude any potential intramolecular end effects. Each aPNA module incorporates five nucleobases for Watson-Crick base pairing to a target nucleic acid sequence. 

The first known example of a mixed p agonist/5 antagonist was a TIPP analogue in which the free C-terminal carboxylate function had been replaced by a carboxamide function [37]. This compound, H-Tyr-Tic-Phe-... 

When JV /V -carbonyldiimidazole (CDI) is reacted with a primary amine in a 1 1 molar ratio, the product is an imidazole-A-carboxamide. However, these compounds dissociate in solution into isocyanates and imidazole even at room temperature,[1] forming a rapidly equilibrating system. Because of this equilibrium, primary imidazole-A-carboxamides can also be prepared from isocyanates and imidazole. 

Cascade Blue cadaverine and Cascade Blue ethylenediamine both contain a carboxamide-linked diamine spacer off the 8-methoxy group of the pyrene trisulfonic acid backbone. The cadaverine version contains a 5-carbon spacer, while the ethylenediamine compound has only a 2-carbon arm. Both can be coupled to carboxylic acid-containing molecules using a carbodiimide reaction (Chapter 3, Section 1). Since Cascade Blue derivatives are water-soluble, the carbodiimide EDC can be used to couple these fluorophores to proteins and other carboxylate-containing molecules in aqueous solutions at a pH range of 4.5-7.5. The reaction forms amide bond linkages (Figure 9.39). 

Other transformations of the substituents on the N-l atom were also reported <1997JOC7288> (Scheme 9) hydrolysis of the 5-cyano group of derivative 29 to a carboxamide 30 has also been reported. 

In the HMBC spectrum this NH proton exhibited 3/(CH) correlation to the C3" (5174.15) and 2/(CH) interaction to the C13 (5165.48) carbonyl, the latter in turn showing 2/(CH) interaction with H12(56.05). Thus it became clear that a carboxamide group linked the conjugated triene and the cyclopentenone unit. A 2/(CH) coupling of the triene terminus H7 to C4 (5jj/5c 5.86/71.20) established the point of attachment of the triene unit to C4. An observed NOE interaction between the H7 and H5 lent further support to this attachment and was suggestive of proximal orientation of the trans-A1 bond to the epoxy unit in the most preferred conformation. The absolute configuration at C4 was not established. 

Fuzeon (enfuvirtide) is an anti-HIV drug. It interferes with the entry of HIV into the CD4 cell. It is a synthetic peptide with 36 amino acids, the N terminus is acetylated while the C terminal forms a carboxamide. The peptide binds to the gp41 subunit of the HIV envelope glycoprotein and prevents the HIV from fusing with CD4. 

Experimental Procedure 2.1.2. Preparation of a Chromium Carbene Complex from a Carboxamide [(4)-2,2-Dimethyl-4-phenyloxazolidin-3-yl]methylene pentacarbonylchromium [126]... 

Asparagine (Asn or N) ((2S )-2-amino-3-carbamoyl-propanoic acid) is a polar, uncharged amino acid with the formula HOOCCH(NH2)CH2CONH2. It has a carboxamide as the side chain s functional group. Asx or B represent either Asn or Asp. Asn are often found near the beginning and end of alpha-helices, and in turn motifs in beta sheets. ... 

A very significant mortality in Western countries is associated with cardiac arrhythmias Consequently an intensive search is underway for agents to combat this condition - particularly for compounds with an unusual mode of action A class Ic (local anesthetic-like) agent of interest in ihis context is Indecainide (50) One of several routes to this compound covered by patents begins with sodium amide mediated alkylation of 9 cyanofluorene (48) with 3 isopropylamino-1 chloropropane to give amine 49 The synthesis concludes by partial hydrolysis of the nitnle func tion to a carboxamide linkage with sulfunc acid to produce indecainide (50) [15]... 

Halogen displacement in 2,3-dihalogeno-l,4-oxathiins has been exploited. An intramolecular approach with a carboxamide function as nucleophile affords the bicyclic /3-lactam 97 <1999H(50)713>. An intermolecular substitution with sodium A,A-dimethyldithiocarbamate in acetonitrile was also reported to give 98 after HBr elimination <1996S198>. 

Peptides are oligomers or polymers of amino acids linked together by a carboxamide group. An example of a pentapeptide is... 

When an amino group is adjacent to a carboxamide group, annulation usually leads to a pyrrolo[2,3-r/ pyrimidin-4-one 164. Such is the case when 163 is allowed to react with aliphatic carboxylic esters (Equation 61) <1996H(42)691>. 

The first synthesized concave bases, the concave pyridine bislactames 3 (Structures 1), possess two amide groups in each molecule. The rotational barrier for a carboxamide bond is ca. 75 kJ/mol [12b, 19]. Therefore at room temperature, E-and Z-forms are observed in the NMR spectra. Because each concave pyridine bislactame 3 contains two amide groups, diastereoisomeric conformers are observable (see Fig. 2). Structures 5 show the ZZ-, EZ- and -conformers for the concave pyridine 3c. 

The benzodiazepines are widely used sedative-hypnotics. All of the structures shown in Figure 22-2 are 1,4-benzodiazepines, and most contain a carboxamide group in the 7-membered heterocyclic ring structure. A substituent in the 7 position, such as a halogen or a nitro group, is required for sedative-hypnotic activity. The structures of triazolam and alprazolam include the addition of a triazole ring at the 1,2-position. 

Stereoselective hydrogenations. The stereochemistry of the hydrogenation of a double bond catalyzed by this Ir(I) complex is markedly controlled by the presence of a carboxamide group. The effect is attributed to coordination between the CONH group and iridium. Reductions of the same substrates with Pd/C show no stereoselection.2... 

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