Hydrolysis of the carboxamide

Alkaline hydrolysis of the carboxamide derivatives 142 upon heating in 1M KOH at reflux afforded the N-3-unsubstituted bicycle 143 (Equation 8) <1992FA1021>. Methanolic ammonia has also been used to remove the N-3-substituent from 144 giving 145 (Equation 9) <1996USP5508154>. 

Oxidation to the sulfoxide and hydrolysis of the carboxamide bond appeared to be the two primary reactions. 

A number of diarylmethyl alkylpiperazines, such as, for example lidoflazine, have found use as coronary vasodilators for the treatment of angina. The most recent of these interestingly incorporates a 2,6-dichloroaniline moiety reminiscent of antiarrhythmic agents. Treatment of the piperazine carboxamide 124 with acetone leads to formation of the nitrogen analogue of an acetal, the aminal 125. Alkylation of the remaining secondary nitrogen with chloroamide 126 leads to the intermediate 127. Exposure to aqueous acid leads to hydrolysis of the aminal function... 

On the other hand, the reaction of 3-,sec-aminophenols (71) with phthalic anhydride does not give the corresponding keto acids (72). The keto acids (72) having a secondary amino group at 4-position are prepared by the reaction of 3-sec-aminophenols (71) with phthalimide at 150-220°C in the presence of boric acid, followed by hydrolysis of the intermediate carboxamide with aqueous sodium hydroxide (Eq. 3). 

The carboxyl group of 2-[4-(4-carboxybenzoyl)benzyloxy]-3-methyM77-pyrido[l,2- ]pyrimidin-4-one, prepared by hydrolysis of the methyl ester, was reacted first with (Et02C)20 in DMF at room temperature and then with 4-phenylpiperazine and 4-piperidinopiperidine to give the appropriate amide derivatives <1996EPP733633>. The N-substituted derivatives of 4-oxo-477-pyrido[l,2-tf]pyrimidine-3-carboxamides and -3-acetamides and 1,6-dimethyl-4-oxo-l,6,7,8-tetrahydro-477-pyrido[l,2-tf]pyrimidine-3-carboxamide were prepared by treatment of the appropriate... 

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. 

This enzyme [EC 3.5.4.10] catalyzes the hydrolysis of the purine ring of IMP to produce 5-formamido-l-(5-phosphoribosyl)imidazole-4-carboxamide. 

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]... 

The reduced basicity of phenothiazine nitrogen requires that even acylation proceed via the anion. The amide (34-2) from the methyl thioether (34-1) can be prepared, for example, by sequential reaction with sodium amide and acetic anhydride. Oxidation of that intermediate with peracid proceeds preferentially on the more electron-rich alkyl thioether to give the sulfone this affords the phenothiazine (34-3) on hydrolysis of the amide. Complex side chains are most conveniently incorporated in a stepwise fashion. The first step in the present sequence involves reaction of (34-3) as its anion with l-bromo-3-chloropropane to give (34-4). The use of that halide with alkylate piperidine-4-carboxamide (34-5) affords the antipsychotic agent metopimazine (34-6) [35]. 

The alkaline hydrolysis of the l,4-benzodiazepin-2-one (236) and its 4-oxide resulted in ring opening via amide cleavage. Similarly treatment with methylamine gave (246) which proved to be a useful intermediate in the synthesis of the 3-carboxamide (247). 

The 5,7-dioxopyrimido[4,5-rf]pyrimidine-5,7-dione (254) can be obtained by fusion of the amide (253) with urea (68JMC568). This amide is prepared by hydrolysis of the corresponding cyanopyrimidine in concentrated sulfuric acid. 4-Aminopyrimidine-5-carboxamides can also be condensed with alkyl and aryl esters to give pyrimido[4,5-d]pyrimidin-4-ones... 

In recent years there has been considerable interest in the reactions of nitriles in the coordination sphere of metal ions. Breslow et al.312 first reported that the hydrolysis of 2-cyano-l,10-phenanthro-line to the corresponding carboxamide is strongly promoted by metal ions such as copper(II), nickel(II) and zinc(II). Base hydrolysis of the 1 1 nickel complex is 107 times faster than that of the uncomplexed substrate. The entire rate acceleration arises from a more positive value of AS. Somewhat similar effects have been observed for base hydrolysis of 2-cyanopyridine to the corresponding carboxamide. In this case rate accelerations of 109 occurred with the nickel(II) complex.313... 

The derivatives (32), (33), and (56) have been prepared by cyclization of the diazonium salts of the appropriate 5-amino-1,2,3-triazoles (55) (Scheme 3). 2,8-Diazaadenine-l-Ar-oxide (32) is formed in 60% yield from the amidoxime (55 X = NOH, R = H), which is made by hydrolysis of 8-azaadenine-1-TV-oxide <60JA3189>. 2,8-Diazahypoxanthine (33) was obtained as a dihydrate in good yield by diazotization of the carboxamide (55 X = O, R = H). The intermediate diazonium salt could be isolated and cyclized rapidly under alkaline conditions <61J0C2396,66JMC733). 2,8-Diazaa-denosine (56) is formed in low yield by diazotization of the carboxamidine (55 X = NH, R = / -d-ribofuranosyl) <72JMC182>. 

The resistance of the furoxan ring to chemical attack allows derivatives to be prepared via the reactions of the substituents (Section 4.22.3.4). Carboxylic acids are available by permanganate oxidation of methyl derivatives or by hydrolysis of the corresponding esters reaction with ammonia affords carboxamides. Acylfuroxans provide a source of hydroxyalkyl compounds by reduction, and oximes, for example, via nucleophilic addition. Acylation and oxidation of aminofuroxans allows the amide and nitro derivatives to be prepared. Nucleophilic displacements of nitro substituents can take place, but can be somewhat hazardous on account of the explosive nature of these compounds. Alkoxy derivatives are formed with sodium alkoxide, while reaction with thiolate anions yields sulfides, from which sulfones can be synthesized by peracid oxidation. Nitrofuroxans have also been reduced to... 

Treatment of 1-cyanoformamidinebenzhydrazide (11) with boiling acetic acid produces 2-phenyl-l,3,4-oxadiazole-5-carboxamide (12) with elimination of NH3 and partial hydrolysis of the CN group, together with 3-cyano-5-phenyl-1,2,4-triazole (13).51 The thermal... 

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. 

The 3-methyl group of 3-methyl-[l,2,4]triazolo[4,3-a]pyridine was inert to metalation and could not be condensed with benzaldehyde (66JOC265). Attempts to make the 3-carboxylic acid (100) by hydrolysis of the 3-carboxamide (101) led instead to (1) by an apparent decarboxylation of the intermediate (100) (66JOC251). 

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