Amide heterocyclic amines

Although acetonitrile is one of the more stable nitriles, it undergoes typical nitrile reactions and is used to produce many types of nitrogen-containing compounds, eg, amides (15), amines (16,17) higher molecular weight mono- and dinitriles (18,19) halogenated nitriles (20) ketones (21) isocyanates (22) heterocycles, eg, pyridines (23), and imidazolines (24). It can be trimerized to. f-trimethyltriazine (25) and has been telomerized with ethylene (26) and copolymerized with a-epoxides (27). 

Other heterocyclic amines used for the synthesis of amides include, among others, 4-amino-1,2,3-trimethylpyrazolone (27%) and 6-aminoindazole (15%). 

In 2002, Leadbeater and Torenius reported the base-catalyzed Michael addition of methyl acrylate to imidazole using ionic liquid-doped toluene as a reaction medium (Scheme 6.133 a) [190], A 75% product yield was obtained after 5 min of microwave irradiation at 200 °C employing equimolar amounts of Michael acceptor/donor and triethylamine base. As for the Diels-Alder reaction studied by the same group (see Scheme 6.91), l-(2-propyl)-3-methylimidazolium hexafluorophosphate (pmimPF6) was the ionic liquid utilized (see Table 4.3). Related microwave-promoted Michael additions studied by Jennings and coworkers involving indoles as heterocyclic amines are shown in Schemes 6.133 b [230] and 6.133 c [268], Here, either lithium bis(trimethylsilyl)amide (LiHMDS) or potassium tert-butoxide (KOtBu) was em-... 

A2 Planar poly (hetero)-aromatic amines and amides Caffeine Furafulline TCDD, PAHs Many heterocyclic amines... 

Heterocyclic amines have also been used for aminolysis. Subsequent cyclization of the acylamino amides leads to imidazolones that show a diverse range of biological activities as antibacterial, antifungal, antiviral, antihelmintic, and anti-Parkinsonian agents, as well as central nervous systems (CNS) stimulants. 

The reaction of A-(2,2-dimcthyl 4-oxo-thictan-3-yl)-acetamide 26 with complex heterocyclic amines 27a-d, cyanoguanidine derivatives 27e-f, or a sugar derivative, namely 1-amino-1-deoxy-D-fructopyranose 27g, in various conditions resulted in cysteine amide derivatives 28a-g in satisfactory yields (Table 2) <2000BML1347, 2001T7173, 2001T825, 2002BMC2303>. 

The resulting alkyl or aryl diethyl phosphates were selectively detected at the 10-25 ng level with the P-mode FPD. Similarly, Jacob et al (36) used dimethyl thiophosphinic chloride in the presence of excess triethylamine to convert primary aliphatic, aromatic and heterocyclic amines to the corresponding N-dimethyl-thiophosphinic amides. The excess reagent was easily removed by treating the reaction mixture with methanol-sodium hydrogen car-... 

F. Mixed Complexes between Chiral Lithium Amides containing Amines and Lithiated Heterocycles... 

Acetylation is an important metabolic route for aromatic and heterocyclic amines, hydrazines and sulphonamides. An amide bond is formed between the amino group of the chemical and the acetate. This reaction is catalyzed by acetylases, the acetyl group being donated by acetyl CoA. 

Many amides have been prepared from pyrazinecarboxylic acid chlorides some are listed below with the relevant amines and references 2-chlorocarbonyl [MeNHj/ EtOAc (138) Me NH/EtOAc (138) BujNH etc/EtOAc (138) aniline/EtOAc (138, 1335) other aromatic and heterocyclic amines/EtOAc (138) sulfanilamide/ pyridine (1336) p-(2 -aminoethyl)benzenesulfonamide (1385) p-anisidine/benzene (1334) 4-hydroxypiperidine/benzene chloroform (1386) morpholine/DMF/20° (1387) 2-aminopyrimidine/benzene (1388) glycine/NaOH/ether (1201, cf. 1333, 1360)] 2-chlorocarbonyl-5-methyl [MeNHj/benzene (1337) MejNH/benzene (1337) 4-phenylpiperazine or diethanolamine/benzene-chloroform (1386) 2-chlorocarbonyl-3-phenyl (6-aminopenicillanic acid) (1024) 2-chloro-3-chloro-carbonyl (morpholine/benzene) (838) 2-chloro-5-chlorocarbonyl (NH4OH) (839) 2-chloro-6-chlorocarbonyl (Et2NH/benzene) (870, 1389) 2-chlorocarbonyl-5-hydroxy (aniline/benzene) (1055) 2-chlorocarbonyl-3-methoxy (morpholine/ benzene) (867) 2-chlorocarbonyl-5-methoxy (morpholine/benzene-chloroform) (1386) and 2-(l -chlorocarbonylethyI) (morpholine/benzene) (364). 

In addition to the construction of the amidine structure iV-alkylation reactions can occur,ring opening in the case of heterocyclic amines and formylation of acidic methylene or methyl groups. 76i,793 jjjg reaction of formamide with excess /V,N-dialkylformamide acetals deviates from this reaction pattern, here azavinylogous formamide acetals (358 Scheme 62) are formed. A, A -Dialkyl-iV -formylformamidines (359) can be prepared either by action of A, N-dialkylformamide acetals on bis(trimethylsilyl)formamide or by treatment of azavinylogous amide acetds (358) with trimethyl-chlorosilane. ... 

In the presence of alkoxides chloroform reacts with secondary amines or aziridines to yield a mixture of aminal esters (486), amide acetals (487) and tris(dialkylamino)methanes (488 equation 224). Predominantly aminal esters (489 equation 225) are formed in the reaction of dchloromethyl ether with aziridines and sodium hydioxide. The heterocyclic aminal ester (491 equation 226) was prepared from the perimidine (490) and triethyl orthoformate. ... 

Lithium amide has been used in place of sodamide for the preparation of heterocyclic amines with antihistaminic activity. For example, a mixture of 2-amiuo-pyridine, /3-dimethylaminoethyl bromide hydrobromide, and 2 equivalents of lithium amide is refluxed in toluene for 22 hrs. Kaye, who notes that lithium amide... 

BU4NF, THF, rt-reflux, 75-98% yield. This method is specific for electron-deficient amines such as heterocyclic amines and electron poor anilines. Because TBAF contains about 4% water and is considered basic, some amides are also cleaved. 

Another useful synthetic route to amides 25 utilized the methyl ester (12 R = Me) prepared by ring expansion of the corresponding benziso-thiazoline ester 8 (R = OMe).9 Methylation of 12 produced ester 28. Combination of various amines with ester 28, or the corresponding ethyl ester, gives analogs of compound 25.7,817,18 The use of heterocyclic amines in this reaction has produced the N-heterocyclic amides sudoxicam (20)19 and piroxicam (29),2 0 21 potent anti-inflammatory agents that are discussed more fully in Section II,D. 

Compound 141 produced broad spectra at room temperature, due to slow rotation of about the N-CO bond of the two A-methyl tertiary amides. Spectroscopic studies were therefore carried out at 50°C, at which temperature sharp, well-resolved spectra were obtained. Cleavage of the crotyl ester and preparative TLC removed most eontaminants from 142, which, however, strongly retained Ph3P=0 (from the Pd catalyst). It was difficult to completely eliminate this contaminant, but at this juncture we were not overly concerned about its presence. In fact, a Russian group had found that certain heterocyclic amine A-oxides act as nucleophilic... 

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