Amidine derivatives

Other amino substituted isoxazoles undergo ring-opening reactions on treatment with base. Thus the amidine derivative (249) gave the triazole (250) (64TL149), while the triazene (251) on reaction with ammonia gave the tetrazole (252) (64X461). 

In the 1880s, Pinner found that the amidine derivative 2 reacted with acetoacetic ester (4) to furnish 2-substituted-6-hydroxy-4-methylpyrimidine 5. The condensation of amidine derivative 2 with other (l-keto esters, malonic esters, and (l-diketones proceeded similarly (see the following pages for examples). ... 

The Cp Ti(amidinate) fragment provides a particularly useful platform for the synthesis of novel titanium imido complexes and the study of their unusual reactivity. Numerous single-, double-, and cross-coupling and imido-transfer reactions were investigated using these compounds. The synthetic routes leading to CpTi and Cp Ti amidinate derivatives are outlined in Scheme... 

Treatment of the bis(amidine) derivatives with a strong base such as Bu Li leads to conversion to the corresponding amidinato(amidine) complexes which on further reaction with triethylphosphine loose the coordinated free amidine as illustrated in Scheme 125. ... 

Reaction of Na[FcC(NCy)2l with CpFe(CO)2l afforded the carbamoyl derivative CpFe(CO)[FcC(NCy)N(Cy)C(0)] (Scheme 136). Although not thermally labile, a CO ligand is readily lost on UV irradiation to give the amidinate derivative CpFe(CO)[FcC(NCy)2]- The addition of CO (SOpsig) to a solution of... 

A series of lithium amidinates derived from (lf ,2i )-frfl s-l,2-diaminocyclo-hexane has been synthesized and structurally characterized. The sjmthetic routes are summarized in Scheme 200. ° ... 

N., A potent inhibitor of inducible nitric oxide synthase, ONO-1714, a cyclic amidine derivative, Biochem. Biophys. Res. Commun. 270 (2000), p.663-667... 

N-Methyl-AT-(substituted phenyl )formamidine was reacted with EMME in boiling toluene for 3 hr to give amidine derivatives (193) in poor yields (80EUP15440). 

The ring closure of the amidine derivative (1328) in refluxing ethanol in the presence of sodium ethylate afforded pyrimidin-4(3//)-one (1329) (59BCJ188). 

Factors influencing the choice of synthetic routes to pyrimidines depend very much upon the substitution pattern of the desired product. For pyrimidines unsubstituted at the 4- and 6-positions, a two-component ring synthesis reaction involving a 1,3-dialdehyde and a urea or amidine derivative is the most straightforward route, but only if the dialdehyde is readily available. For example, synthesis of 2-chloro-5-(2-pyridyl)pyrimidine 989, an intermediate in the synthesis of a selective PDE-V inhibitor, was achieved in two steps in 40% overall yield by condensation of 2-(2-pyridyl)malondialdehyde 987 with methylurea, followed by demethylation/chlorination of the pyrimidinone 988 with a mixture of POCI3 and PCls <20070PD237>. 

The halonitro compounds and the methanol used were of purum or pract. quality from Fluka. The amidine derivatives (in the form of their salts) were purchased from Fluka or Aldrich (purum or pract.). The N,N-dialkyl-formamidine acetates were prepared by analogy to a published procedure (ref. 8) from cyanamide and used as isolated (containing ca. 10% ammonium acetate). 

Amidine derivatives are effective dehalogenation inhibitors for the chemoselective hydrogenation of aromatic halonitro compounds with Raney nickel catalysts. The best modifiers are unsubstituted or N-alkyl substituted formamidine acetates and dicyandiamide which are able to prevent dehalogenation even of very sensitive substrates. Our results indicate that the dehalogenation occurs after the nitro group has been completely reduced i.e. as a consecutive reaction from the halogenated aniline. A possible explanation for these observations is the competitive adsorption between haloaniline, nitro compound, reaction intermediates and/or modifier. The measurement of the catalyst potential can be used to determine the endpoint of the desired nitro reduction very accurately. 

A proton NMR study by Mirek and Bogdanowicz-Szwed128 observed that the 5-proton was significantly deshielded in 3-amide, -thioamide, and -amidine derivatives, and this established the preferred conformation as 83. 

Cyanopyrazines react with aromatic amines in the presence of aluminum chloride as catalyst at temperatures below 200° and give amidine derivatives in good yield [Eq. (14)].228 Hydrogenation of... 

A method has been developed for distinguishing between the possible structural types of adducts for guanidine and amidine derivatives with DMAD using 13C NMR spectroscopy. The 5,6-dihydroimidazo[2,l-5]thiazol-3(2iJ)-one (237) is of interest since it contains an sp3 carbon atom attached to two nitrogen, one oxygen, and one sulfur atom and this leads to very low-field 13C resonances (5114.6) (81JCS(Pl)4l5). 

Unprecedented dihydrodipyridopyrazines were easily obtained by hetarynic dimerization of 2-alkylamino-3-halopyridines <02T3513>. The reaction of hexamethylphosphotriamide with amidines derived from Af-benzimidazoyl imidates 81 afforded benzimidazolo-1,3,5,2-triazaphosphorine 2-oxides 83 in good yield. When the condensation was carried out at room temperature /V-phosphonic amidines 82 could be isolated <02PS1033>. 

Baumeister et al. studied the hydrogenation of various halonitrobenzenes using Raney Ni modified with amidine derivatives.115 Formamidine acetate (19b) has been found to be the most effective inhibitor for dehalogenation. It has been shown that the dehalogenation occurs as a consecutive reaction after the halogenated aniline has been formed. A typical example with use of this inhibitor is shown in eq. 9.51 for the hydrogenation of l-chloro-2,4-dinitrobenzene in comparison with dicyandiamide. It is noted that the reaction time could be shortened with 19b compared to that with 19a. 

In the sense of an inter molecular amination with heterocyclic amidine derivatives, such as amino azines and diazines, and 2-chloro-3-iodopyridines followed by an intramolecular amination, Maes and coworkers [93] have established a facile synthesis of dipyrido[l,2-a 3, 2 -d]imidazole and its benzo-and aza-analogs 101-106 (Scheme 36). 

In a recent publication, amidine derivatives of a cyclic enaminone are used as the heterodiene component in a Diels-Alder reaction with diethyl maleate to yield 5-quinolones203 (equation 145). 

The reaction of amines and ketene acetals was used as a main synthetic approach to 1,1-enediamines in earlier years72. Both simple and conjugated 1,1-enediamines can be obtained by this route. Displacement reaction of ketene acetal 34 with two equivalents of piperidine furnishes 1,1-dipiperidinoethene (35) in 62% yield (equation 9)73. Primary amines and ammonia react with 34 to give amidine derivatives. Cyano-74 and trifluor-oacetyl-substituted enediamines75 have been synthesized from the corresponding ketene acetals in good to excellent yields (e.g. equation 10). 

Amidine derivatives, (IV), prepared by Pitzele (5) were effective as nitric oxide synthase inhibitors and used in the treatment of hypertension and thrombosis. 

Treatment of amidine derivative 609 with elemental sulfur in the presence of piperidine gives fused thiophene 611 via cyclization of the intermediate 610 (Scheme 91) <1998JCM294>. Saccaride-substituted thiophenes 613 <2005CAR547> and 2,2-dioxo-17/-thieno[3,4-z][l,2]thiazines 615 <1998JHC1449> are synthesized by the reaction of saccharide derivative 612 and l,l-dioxo-l,2-thiazines 614 with sulfur in the presence of Et3N. 

As shown by X-ray structure determination (Fig. 3), 7 does not contain a hexacoordinated silicon atom stabilized by amidinate ligands but rather may be regarded as an amidine derivative with a tetracoordinated silicon atom. 

Sondhi SM, Rani R, Roy P et al (2010) Conventional and microwave assisted synthesis of small molecule based biologically active heterocyclic amidine derivatives. Eur J Med Chem 45 902-908... 

Imidazoles (1) prepared from amidines derived from o -amino acids ... 

Imidazole-4-carboxylates have been made from amidines derived from or-ainino acids (see Section 2.2.1 and Table 2.2.1), by Claisen rearrangement of the adduct formed when an arylamidoxime reacts with a propiolate ester (see Section 2.2.1 and Scheme 2.2.6), from a-aminocarbonyls with cyanates or thiocyanates (see Section 4.1 and Table 4.1.1), from a-oximino- 6-dicarbonyl compounds heated with an aUcylamine (see Section 4.1 and Scheme 4.1.7), and by anionic cycloaddition of an alkyl isocyanoacetate to diethoxyacetonitrile (see Section 4.2 and Scheme 4.2.11 see also Scheme 4.2.12). A further useful approach is to use an appropriate tricarbonyl compound with an aldehyde and a source of ammonia (see Chapter and Scheme 5.1.1). Irradiation of 1-alkenyltetrazoles bearing an ester substituent may have applications (see Section 6.1.2.3). 

---