Synthesis of 1,3-bifunctional cyclobutane derivatives with α-CHF2/CF3 group – advanced building blocks for medicinal chemistry

Multigram Synthesis of α‐ and γ‐((Hetera)cyclo)alkylpyridines through α‐Arylation of (Hetero)aliphatic Nitriles

“…[40] Indeed, oxidation of these products with RuCl 3 À NaIO 4 provided cyclobutanones 15 a-d in 70-80 % yields (Scheme 4, A). [41,42] The same reagent was used to oxidize the thioether moiety in tetrahydrothiopyran derivatives 7 d, 7 j, 7 r, and 7 w, which gave sulfones 16 a-d in excellent yields (79-86 %) (Scheme 4, B). [42] Finally, directed lithiation of pyridine 3 aa and subsequent quenching of the obtained organometallic intermediate with I 2 resulted in trisubstituted pyridine 18 in 64 % yield (Scheme 4, D).…”

“…Thus, the terminal double bond of compounds 3 e , 7 f , 7 p , 7 x was considered as a “masked” carbonyl group [40] . Indeed, oxidation of these products with RuCl 3 −NaIO 4 provided cyclobutanones 15 a – d in 70–80 % yields (Scheme 4, A ) [41,42] . The same reagent was used to oxidize the thioether moiety in tetrahydrothiopyran derivatives 7 d , 7 j , 7 r , and 7 w , which gave sulfones 16 a – d in excellent yields (79–86 %) (Scheme 4, B ) [42] …”

Synthesis of new derivatives of functionally substituted cyclobutanecarboxylic acids as potential neuromodulators

“…After purification on a column (1.8 x 50 cm, silica gel 40 g, eluent-hexane: ether =10:1), 2.95 g (69 %) of 3 ester was isolated in the form of colorless crystals, mp=115-117 °C. 1 Н NMR spectrum, δ, ppm (J, Hz): 1.00 (3H, s, cis-H 3 CC-CCOO-); 1.30 (3H, s, trans-H 3 CC-CCOO-); 2,74 (1H, d, J=2.40, ≡CH); 4.39 (1H, d, J=9.86, CHCl); 4.52 (1H, d, J=9.86, CHCCl 3 ); 6.53 (1H, d, J=2.40, OCH); 7.38-7.61 (5H, m, C 6 H 5 ). 13 C (75.5 MHz, CDCl 3 ) δ, ppm: 166.0; 135.5; 129.7; 128.9; 128.2; 95.3; 78.9; 76.8; 70.4; 68.1; 62.4; 59.7; 47.4; 23.0; 20.7.…”

“…=154-156 °C. 1 На основе функционально замещенной циклобутaнкарбоновой кислоты, сконструированной методом ATRC (Радикальная Циклизация с Переносом Атома) полигалогенгексеновой кислоты в присутствии аминных комплексов меди(I) синтезированы две новые производные. Структурные особенности: гем-диметильные, трихлорметильные и карбонильные группы, присоединенные непосредственно к малым напряженным карбоциклам, делают их потенциально активными в качестве агонистов нервных натриевых каналов и рецепторов GABA, NMDA.…”

“…Cyclobutanecarboxylic acids and their derivatives are present as structural units in various biologically active molecules [1,2]. The derivatives of these molecules themselves are potential candidates for binding to specific receptors in the brain, as well as for modulating the activity of the GABA or NMDA receptors, which is extremely important for the search for new drugs for the treatment of specific neurological diseases [3].…”