Heterocycles, synthesis dimethylamino

Phosphonium hexafluorophosphate, benzotriazolyl-N-hydroxytris(dimethylamino)-in peptide synthesis, 5, 728 Phosphonium salts chromene synthesis from, 3, 753 reactions, 1, 531 Phosphonium salts, vinyl-in pyrrole synthesis, 4, 343 Phosphonium ylides in heterocyclic synthesis, 5, 165 Phosphoramide, triethylene-as pharmaceutical, 1, 157 Phosphoramide, triethylenethio-as pharmaceutical, 1, 157 Phosphorane, pentaphenyl-synthesis, 1, 532 Phosphoranes, 1, 527-537 Berry pseudorotation, 1, 529 bonding, 1, 528... 

In a recent study, another method for microwave-assisted heterocycle synthesis leading to a small set of imidazole derivatives has been reported [54], These pharmaceutically important scaffolds were synthesized utilizing polymer-bound 3-N,N-(dimethylamino)isocyanoacrylate. This polymer support was easily prepared by treatment of [4-(bromomethyl)phenoxy]methyl polystyrene with a twofold excess of the appropriate isocyanoacrylate potassium salt in N,N-dimethylformamide (Scheme 7.37). The obtained intermediate was subsequently treated with N,N-di-methylformamide diethyl acetal (DMFDEA) in a mixture of tetrahydrofuran and ethanol to generate the desired polymer-bound substrate. 

Microwave-assisted heterocycle synthesis has also been used to prepare a small set of pharmaceutically important imidazole derivatives [54]. The procedure utilized an initially prepared polymer-bound 3-N,N-(dimethylamino) isocyanoacrylate. The best results in imidazole synthesis were obtained by microwave-assisted reaction of an eightfold excess of the polymer-supported isonitrile suspended in 1,2-dimethoxyethane (DME) with the corresponding amines (Scheme 16.31). Cleavage with 50% trifluoroacetic acid in dichloromethane afforded the desired heterocyclic scaffolds in moderate yields. 

Substituted 3-dimethylamino- and 3-cyanopropenoates in the synthesis of heterocyclic systems 99JHC1581. 

In 1979, Schollkopf et al. " formed a-isocyano- 3-dimethylamino-acryl methyl esters 86, and Bienayme prepared many similar isocyanides,which can undergo a variety of heterocycles, forming reactions like the synthesis of 88 from 84-87 (Scheme 1.20). 

Nizatidine Nizatidine is N-[2-[[[2-[(dimethylamino)methyl]-4-thiazolyl]methyl] thio] ethyl]-2-nitro-l,l-ethenediamine (16.2.15). According to its chemical structure, nizatidine is somewhat of a hybrid structure of ranitidine and famotidine, in which a side chain of ranitidine and carrying heterocycle, 2-aminothiazol, are used. Likewise, its synthesis also is a specific combination of pathways used for making both prototype drugs. 2-(Dimethyl-aminomethyl)-4-hydroxymethylthiazol serves as the initial compound, from which the desired nizatidine (16.2.15) is synthesized by subsequent reaction with 2-mercaptoethy-lamine hydrochloride and then with iV-methyl-l-methythio-2-nitroethenamine [71,72]. 

Fisch et al. reported the synthesis of a 1,2,4,5-tetraborinane heterocyclic compound 19 which was stabilized by dimethylamino groups (Scheme 4) and showed a raido-structure (Fig. 2).53... 

The first synthesis of phenothiazine was reported by Bernthsen about 80 years ago. In the evolution of the chemistry of this heterocycle, three periods can be discerned. First, phenothiazine was of interest owing to its quinonoid derivatives—an important chapter in sulfur dye chemistry. Research work in the field of phenothiazine was then stimulated by the discovery of the anthelmintic action of unsubstituted and of some C -substituted phenothiazines. During the last two decades, the exceptional pharmacological properties of some A-substituted phenothiazines, e.g., the antihistaminic activity of promethazine, 10-(2-dimethylamino-l-propyl)phenothiazine, and particularly the psychotherapeutic action of chlorpromazine, 2-chloro-10-(3-dimethylamino-1 -propyl )phenothiazine, focused interest mainly on the synthesis and testing of a great number of compounds of this type. The phenothiazine drugs now play a very important part in chemotherapy. 

Vinamidinium salts are important intermediates in the synthesis of heterocycles. The 2-chloro-l,3-bis(dimethylamino)trimethinium hexafluorophosphate salt has been used in the preparation of the highly selective Cox-2 inhibitor etoricoxib (Scheme 1). This method describes a straight-forward preparation of the hexafluorophosphate salt which is a crystalline, thermally and shock-stable, non-hygroscopic solid. The submitters have extensively studied the preparation of vinamidinium salts and demonstrated that the method is applicable to substituted acetic acids that contain an electron-withdrawing group (Table 1)." The annulation reaction is also general and useful for the preparation of pyridines, pyridones and pyridine N-oxides. ... 

Our method represents a simple, rapid and high yield preparation of N,N-dimethylamino isocyanate. This interesting intermediate has been the subject of several publications and is useful for the synthesis of a wide variety of heterocycles, carbazates, and other molecules containing a hydrazine group. 

In the presence of a strong base, malononitrile reacts with a dimethylamino-methylene group and forms a ring with a neighbouring lactam carbonyl function, the dimethylamino group being eliminated. The usefulness of nitriles in the synthesis of heterocycles as been reviewed [3332a]. 

Further examples have been added to the range of 2-amino substituted 3-dimethylamino-propenoates which are of value in the synthesis of 2//-pyran-2-ones and other heterocycles <93PHC34,97JHC247, 263, 813>. 

Dialkyl Acetone-1,3-Dicarboxylates and their Mono-and b/s(Dimethylamino) methylidene Derivatives in the Synthesis of Heterocyclic Systems... 

Type G (N—C—S—C—Q Synthesis.—iV-(5-Aryl-l,3-oxathiol-2-ylidene) tertiary iminium salts (33) yield a variety of heterocyclic compounds upon reaction with nucleophiles containing an amino-group. The action of ammonia on (33 RgN = piperidino, morpholino, or dimethylamino), for... 

Fluoromalonaldehyde (25), which exists in solution as the enol form Z configuration), has been condensed with heterocyclic JV -alkylinunonium salts to give y-fluoropentamethinecyanine dyes (see Scheme 23). Synthesis of the aldehyde (Scheme 22) involves hydrolysis of 2-fluoro-3-dimethylamino-acrolein, the product of Vilsmeier formylation of sodium fluoroacetate. - ... 

Burkholder C, Dolbier WR Jr, Medebielle M (1998) Tetrakis(dimethylamino)ethylene as a useful reductant of some bromodifluoromethyl heterocycles. Application to the synthesis of new gem-difluorinated heteroarylated compounds. J Org Chem 63 5385-5394... 

Baraznenok IL, Nenajdenko VG, Balenkova ES (2003) Synthesis of CFs-heterocycles based on 4-dimethylamino-l,l,l-trifluoro-3-buten-2-one. Chem Heterocycl Comp 39 776-779... 

Synthesis of 3-(l-phenylhydrazono-L-threo-2,3,4-trihydroxybutyl)-lH-quinoxalin-2-one 34 was achieved in 86% yield by MW irradiation for 2.5 min of L-ascorbic acid 30 with o-phenylenediamine and phenylhydrazine in the presence of acetic acid (Scheme 34). Another method of synthesis of a fused heterocyclic tetracycle could be obtained from MW irradiation of 2-(N,N-dimethylamino)methylene-5,5-dimethylcyclohexane-l,3-dione and 2-benzimid-azoleacetonitrile (Scheme 35). The reaction proceeds in isopropanol using a catalytic amount of piperidine leading to the formation of tetrahydrobenzimidazo[l,2-fl]quinoline derivative 38 [57]. 

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