Bredereck reagent

Reaction of 434 with the Bredereck reagent gave the enamino ketone... 

The formation of a pyrimido[5,4-f][l,2]thiazine by annulation of a pyrimidine ring onto a benzoH[l,2]thiazin-4-one has been reported, involving condensation with dimethylformamide dimethyl acetal followed by Bredereck s reagent (Scheme 90), and reaction of the resultant vinylogous amide with guanidine <2005W02005/037843>. Essentially, the same approach has been used to prepare annulated forms of the isomeric pyrimido[4,5-< ][l,2]thiazines, as outlined in Scheme 91 <1998W098/28281>. 

Diketone 12 must be condensed with a third, doubly functionalized octahydroacridine unit in the last step of the torand synthesis (cf Scheme 6.1). The following protocols (8-10) describe the three-step synthesis of torand precursor 15 from octahydroacridine 5. The reagents involved in these three steps are shown in Scheme 6.11. According to Protocol 8, octahydroacridine is condensed with benzaldehyde in the presence of acetic anhydride,24 as in the second stage of Protocol 2 (cf Scheme 6.3). The crystalline product 13 precipitates from the reaction mixture in high yield and purity. Ozonolysis of 13 (Protocol 9) is conducted by the method described in Protocol 7 for conversion of 11 to diketone 12 (cf. Scheme 6.10) and the same precautions apply. The product diketone 1425 requires no further purification after removal of benzaldehyde by trituration with diethyl ether. The third octahydroacridine unit is then readied for torand cyclization in Protocol 10 by condensing diketone 14 with Bredereck s reagent, r-butoxybis(dimethylamino)methane,26 which is commercially available. The bis[p-(dimethylamino)]enone product 15 is easily purified by precipitation from ether/dichloromethane. 

Carboxylation. Bredereck s reagent has been used in a simple synthesis of L-y-carboxyglutamic acid (S), an unusual natural amino add present in prothrombin and believed to be involved in elotting. The starting material is the lactam 1 derived from L-glutamic acid and available commercially. It is converted by reaction with this reagent into the enamide 2. Reaction with 2,2,2-trichloroethoxycarbonyl chloride transforms 2 into the trichloroethyl ester 3 in moderate yield. The synthesis of 5 is completed by reaction with benzyl alcohol and triethylamine followed by hy drogenolysis. ... 

Bredereck and Schmotzer (1044), from diaminomaleonitrile (DAMN hydrogen cyanide tetramer) and oxalyl chloride, prepared 2,3-dicyano-5,6-dihydroxy-pyrazine but Stetten and Fox (1049) could not prepare 23-diamino-5-hydroxy-pyrazine from glycine amide and oxamide. Section 11.3 lists preparations from a, -diamino or a, -diimino compounds and reagents other than a,0-dicarbonyl compounds (384) with additional data (1050) and oxidation of 23-dichloro-quinoxaline with hot aqueous potassium permanganate gave 23-dicarboxy-5,6-dihydroxypyrazine (1051). 

Bredereck s [456] reagent, dime- pyrazole thyl formamide synthesis dimethyl acetal (solvent 50 mh for 5 g resin)... 

Generation of a-ketoenamines (Table 8, entry 8) [456] Spivey et al. [456] performed a pyrazole synthesis with a polymer-supported acetophenone and a germanium-based traceless linker. The support-bound acetophenone was allowed to react with dimethylformamide dimethyl acetal (Bredereck s reagent) [498]. Subsequent reaction of the resulting a-ketoenamine with aryl hydrazine hydrochlorides gave the pyrazoles. 

Ethyl 3-[2-(dimethylamino)vinyl]pyridazine-4-carboxylatc, obtained by condensation of ethyl 3-methylpyridazine-4-carboxylate with icrt-buLoxy-/V-ditneLhylmethanediamine (Bredereck s reagent, see Houben-Weyl, Vol. E5, p 151 f), cyclizes with alkylamines in acetic acid to give the corresponding 6-alkylpyrido[3,4-c/]pyridazin-5(6//)-ones 5.7... 

The mixture of eneaminoketones 121 is converted to the corresponding a-diazoketones 122 by alkylation with Bredereck s reagent followed by treatment with p-toluenesulfonyl azide. 7 The adenosine derivative (123) is treated with trifluoromethylsulfonyl azide to provide diazoketone 124 via deamination diazo transfer reaction in 72% yield.48... 

The formamides 16 are intermediates. Formamide (Bredereck variant of the Traube synthesis [149]), formamidine, orthoformic ester, diethoxymethyl acetate, Vilsmeier reagent (fi om DMF and POCI3) and dithioformic acid are used as formic acid derivatives. 4,5-Diaminopyrimidines can be obtained from 4-aminopyrimidines 17 by nitrosation with HNO2 followed by reduction of the nitroso compounds 18 ... 

Immobilization of the required dioxolane-protected 4-Hthioacetophenone, deprotection with pyridinium p-toluene sulphonate (PPTS), and condensation with Bredereck s reagent gave resin-bound enaminone 2. The suitability of resin 2 for H-brary synthesis was verified by a trial condensation with acetamidine hydrochlori-... 

---