Guanidines, alkyl synthesis

T2 resin synthesis of substituted amines, amides(peptides), (thio)urcas, hydrazines, alcohols, esters guanidines alkyl halides, sulfoximines. ... 

Rolgamidine (14) is a dihydropyrrole derivative which has antidiarrheal activity It can be synthesized by alkylation of trans 2,5-dimethyl-3 pyrroline (12) with methyl bromoacefate to give 13 An amide-ester exchange reaction with guanidine hydrochloride completes the synthesis of rolgamidine (14) [3]... 

The synthesis, structures, and reactivity of neutral and cationic mono- and bis(guanidinato)zirconium(rV) complexes have been studied in detail. Either salt-metathesis using preformed lithium guanidinates or carbodiimide insertion of zirconium amides can be employed. Typical examples for these two main synthetic routes are illustrated in Schemes 73 and 74. Various cr-alkyl complexes and cationic species derived from these precursors have been prepared and structurally characterized. 

An alternative to the Gabriel synthesis, in which alkyl halides can be converted to primary amines in good yields, involves treatment of the halide with the strong base guanidine followed by alkaline hydrolysis. There are several alternative... 

An important development of the synthesis described above is derived from the observations of Scott, O Donovan and Reilly [159], which were taken up by others [109]. l-Guanyl-3,5-dimethylpyrazole nitrate reacts with alkyl- and aryl-amines in hot water, ethanol, or without solvent to give good yields of guanidines. Use of this pyrazole nitrate or other salt for obtaining guanidines now competes with older methods if yield and ease of isolation of the product are the main considerations [95, 138, 140, 143, 160-164]. 

Some substituted guanidines have been obtained [457] by reaction of amines with the disulphide H2N(HN )C S S C( NH)NH2. Papers on the structure and p/fa s [458], and the synthesis [458, 459] of acylguanidines have been published. Reaction of guanidine with alkyl-, alkenyl-, and benzyl-halides, followed by distillation under basic conditions, is reported to give useful yields of amines [460]. A novel electrophilic substitution of benzene to give A -methyl-A -phenyl-guanidine amongst other products has been published [461 ]. 

The synthesis of the module is provided in Scheme 10.5 (Kushner et al. 2007). Double alkylation of ethyl acetoacetate followed by guanidine condensation afforded alkenyl-pyrimidone intermediate 24 (Kushner et al. 2007). Isocyanate 25 was coupled to pyrimidone 24 to yield 26. Upon dimerization in DCM, RCM effectively cyclized the two UPy units (Mohr et al. 1997 Week et al. 1999). A one-pot reduction and deprotection through hydrogenation using Pearlman s catalyst gave diol module 27. Finally, capping 27 with 2-isocyanatoethyl methacrylate at both ends provided the UPy sacrificial cross-linker 28, which was thoroughly characterized by H- and C-NMR, Fourier transform IR (FTIR), and mass spectrometry. 

Lehn synthesised guanidinium-based cationic steroids incorporating an acylhy-drazone linker using the approach shown in Fig. 9 [141]. The synthesis was developed from a polyamine scaffold by guanidination of the primary amino groups and alkylation of the secondary amine with methyl chloroacetate to introduce the ester moiety required to form a hydrazide group by reaction with hydrazine monohydrate. Cationic steroid hydrazones were then prepared via an acetic acid catalysed reaction with cholestanones, which demonstrated high transfection efficiency and low toxicity in a variety of cell lines [141]. 

Another key intermediate for pteridine synthesis was also seen in 2-amino-3-ethoxycarbonyl-5-phenylpyrazine 1-oxide which reacts with various amines to form the corresponding amides followed by cyclization with triethyl orthoformate giving 3-alkyl-6-phenyl-4(3/7)pteridinone 8-oxides <87JHC1109>. The synthesis of 2,4-diamino-6-methylpteridine 5-oxide (371) was achieved from 5-methyl-pyrazine-2-carboxamide (366) via the 4-oxide (367), a Hofmann degradation (368), bro-mination (369), and cyanation (370) followed by cyclization with guanidine to give (371) (Scheme 60) <93JHC841>. 

Reaction of carboxamides with isatoic anhydrides 7 in place of anthranilic acid as a source of the anthraniloyl group is an attractive extension of the Niementowski synthesis (cf. p 30). The reaction of isatoic anhydrides 7 with formamide or 2-hydroxybenzamides at elevated temperatures in a melt or in tbe presence of suitable solvents gives high yields of tbe respective quinazolin-4(3//)-oncs 8/ whereas with alkyl-, aralkyl-, or arylcarboxamides the yields of the corresponding 2-substituted quinazolin-4(3//)-oncs arc low Guanidine and ami-... 

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