Thiazole-5-Carboxamide

Compounds (397) can be prepared by reaction of 4-chloro-thiazole-5-carbonitriles with ethyl 2-thioacetate or a 2-thioacetamide <92T7689>. The thieno [2,3-d]thiazole-5-carboxamides (397b) obtained in that way lead to thiazolo[4, 5 4,5]-thieno[3,2-d]pyrimidin-5(6//)-one (398) upon treatment with triethyl orthoformate in acetic anhydride (Scheme 99). 

Thiazole carboxamides are readily dehydrated to nitriles in good yields by heating with phosphorus oxychloride (91), phosphorus pentoxide (87, 71), or phosphoryl chloride (16) (Scheme 19). 

Antagonists of niacin include pyridine-3-sulfonie acid (in bacteria), 3-acetylpyridine, 6-aminonicctinamide, and 5-thiazole carboxamide. Synergists include vitamins Bj, B, B. B]). and D, pantothenic acid, folic acid, and soiualotrupliin (growth hormone). 

Thiabendazole, 2-(4 -thiazolyl)benzimidazoIe (32), is prepared from o-phenylene-diamine and 4-thiazole carboxamide (33) in polyphosphoric acid (Brown et al.,... 

The most important applications of the in situ photochemical fluorodediazoniation start from heterocyclic amines for which the diazonium tetrafluoroborates are impossible to isolate. In this way, fluorinated imidazoles,123-253,254-257 261 benzimidazoles,262 pyrazoles,254-256,262 indazoles,158 thiazoles,259 and triazoles259-262 have been prepared (Table 4). Some of these are the precursors of biologically active compounds such as fluoro-substituted histidines or histamines,123,253-257,258 or 5-fluoro-l/ -D-ribofuranosylimidazole-4-carboxamide.261... 

J 4-Hydroxy-2-methyl-1,1-dioxo-1,2-di hydro-116-benzo[e][1,2]thiazine-3-carboxylic acid (5-methyl-thiazol-2-yl)-amide, 4-hydroxy-2-methyl-A/-(5-methyl-2-thiazoyl)-2H-1,2-benzothiazine-3-carboxamide-1,1 -dioxide, C14H13N3O4S2, Mr 351.40, mp 264 °C (decomp.)... 

S, 7a7 )-l-(rerr-Butoxycarbonyl)-V7-nietbyl-5-oxotetrahydrospirofpyiToliduie-2,6 -pyrrolo-[2,l-b]thiazole]-3 -carboxamide (86) 1"11... 

S, 7a7 )-l-Acetyl-/V7-nietbyl-5 -oxotetrahydrospiro[pyrrolidine-2,6 -pyrrolo[2,l-6]thiazole]-3-carboxamide (87) [m ... 

Oxidation of 5-chlorobenzo[6]thiophene-2,3-quinone with hydrogen peroxide in the presence of ammonia gives 5-chloro- 1,2-benziso-thiazole-3-carboxamide (179d).m... 

Diazoniobenzenesulfonamido)thiazole tetrafluoroborate, 3113 l-(4-Diazoniophenyl)-l,2-dihydropyridine-2-iminosulfinate, 3386 l(2 -Diazoniophenyl)2-methyl-4,6-diphenylpyridinium diperchlorate, 3841 1(2 -, 3 -, or4 -Diazoniophenyl)-2,4,6-triphenylpyridinium diperchlorate, 3864a 3-Diazoniopyrazolide-4-carboxamide, 1418 5-Diazoniotetrazolide, 0545 3-Diazo-5-phenyl-3//-pyrazole, 3112... 

Imidazole and thiazole rings have demonstrated instability under photolysis conditions. For example, the API thiabendazole undergoes cleavage of the thiazole ring to form benzimidazole-2-carboxamide and benzimidazole as well as cleavage of the imidazole ring to form thiazole-4-(7V-carbomethoxy)-carboxamide (Fig. 116) (106). 

Heterocycles were explored as replacements for the nonphenolic ring (Table 3) [19]. Unsubstituted thiazoles, pyridines, and thiophenes gave active agonists, but with little or no selectivity. While an TV-methyl imidazole had little if any opioid agonist activity in this series, often additional substituents on the heterocycles provided potent compounds with delta opioid receptor selectivity. For instance, compound 34, a thiophene with a diethyl carboxamide, displayed selective delta opioid receptor agonism (although no binding selectivity was observed). 

Aminopyrrolidin-1 -yl)-6-fluoro-4-oxo-1 -(thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (13, R = OH) gave the corresponding 3-carboxamide (13, R = NH2) via the unisolated acid chloride (13, R = Cl) (ClC02Et, Et3N then NH3/EtOH 54%).352... 

Preparation of (3/ ,6/ ,7aS)-6-benzyl-6-f-butoxycarbonylamino-5oxohexahydro-pyrrolo[2,l-b]thiazole-3-carboxamide... 

Preparation of 2-(2-morpholin-4-yl-ethyl)-4-trifluoromethyl-thiazole-5-[l-(3-dimethylamine)phenyl]-ethyl-l-carboxamide (general procedure)... 

Ribavirin, USP. Ribavirin is l-j3-o-ribofuranosyl-l.2.4-thiazole-3-carboxamide. The compound is a purine nucleoside analogue with a modified base and a D-riho.se sugar moiety. The. structure of ribavirin is show n below. 

When a 2-su phinyl-carboxamide is warmed with hydrazoic acid, a 3-iminoiso-thiazole I-oxide is formed. 

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