Facile synthesis of novel amino acid-like building blocks by N-alkylation of heterocyclic carboxylates with N-Boc-3-iodoazetidine

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

“…The aforementioned protonated carbons C-3 and C-3’ showed correlations in the 1,1-ADEQUATE spectrum thus allowing to assign a neighboring quaternary carbons C-4 (δ 109.9 ppm) and C-5 (δ 175.4 ppm), H–C(3)–C(4) and H–C(3’)–C(5), respectively. The 1 H, 15 N-HMBC experiment revealed an expected long-range correlation between the 1,2-oxazole methine H-3 proton (δ 8.50 ppm) and nitrogen N-2 which resonated at δ −0.6 ppm, while the azetidine ring protons showed a sole correlation with the azetidine nitrogen N-1’ (δ −311.7 ppm) [ 29 , 39 ].…”

“…Recently, a highly specific and potent p38α kinase inhibitor containing a 3-amino-1-phenyl-1H-pyrazole-4-carboxylic acid residue was identified directly from the 12.6-million-member DNA-encoded small molecule library using yoctoReactor technology [26]. We have developed efficient protocols that provide easy access to highly functional heterocyclic compounds as novel amino acid-like building blocks by combining thiazole, selenazole, pyrazole, indazole, and indole moieties with both carboxyl functional groups and cycloaminyl units [27][28][29][30][31].…”

Convenient Synthesis of N-Heterocycle-Fused Tetrahydro-1,4-Diazepinones

“…It is known that NH-pyrazoles usually exhibit annular N,N-prototropy [38,39]. N-Alkylation of asymmetrically ring-substituted 1H-pyrazoles generally results in the formation of a mixture of regioisomeric N-substituted products [40][41][42][43] and therefore regioselective N-alkylation requires optimization of reaction conditions [44]. Wright et al has reported that alkylation of ethyl 1H-pyrazole-3(5)-carboxylate in the presence of K 2 CO 3 was found to favor the formation of ethyl 1-substituted pyrazole-3-carboxylates while the formation of 1-substituted-1H-pyrazole-5-carboxylates could be sterically redirected by alkylating ethyl 3-(triphenylsilyl)-1H-pyrazole-5-carboxylate and removing the triphenylsilyl group with Bu 4 NF [45].…”

Methyl 2-Amino-4-[1-(tert-butoxycarbonyl)azetidin-3-yl]-1,3-selenazole-5-carboxylate

“…The multiplicity-edited 1 H- 13 C HSQC spectrum revealed a cross-peak correlating a methine proton at 4.67 ppm with the 13 C signal at 28.1 ppm from the azetidine ring (Figure 3). The aim of the present study was to extend our previous work on heterocyclic amino acids containing selenazole and azetidine cores [11][12][13][14], as it is still a new and potentially relevant field. In this work, a molecular system containing both selenazole and azetidine scaffolds was synthesized through Hantzsch cyclization of β-ketoester.…”