Synthesis of Isomeric 6-Trifluoromethyl-3-azabicyclo[3.1.0]hexanes: Conformationally Restricted Analogues of 4-Trifluoromethylpiperidine

Olexiy S. Artamonov; Evgeniy Y. Slobodyanyuk; Oleg V. Shishkin; Igor V. Komarov; Pavel K. Mykhailiuk

doi:10.1055/s-0032-1316831

Synthesis, Table of Contents

Synthesis 2013; 45(2): 225-230
DOI: 10.1055/s-0032-1316831

paper

Synthesis of Isomeric 6-Trifluoromethyl-3-azabicyclo[3.1.0]hexanes: Conformationally Restricted Analogues of 4-Trifluoromethylpiperidine

Olexiy S. Artamonov

^aInstitute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanska Street 5, Kyiv-94 02660, Ukraine

,

Evgeniy Y. Slobodyanyuk

^bEnamine Ltd., Vul. Oleksandra Matrosova 23, 01103 Kyiv, Ukraine Email: Pavel.Mykhailiuk@gmail.com

^cDepartment of Chemistry, and Kyiv National Taras Shevchenko University, Vul. Volodymyrska 64, Kyiv 01033, Ukraine

,

Oleg V. Shishkin

^dSTC, ‘Institute for Single Crystals,’ National Academy of Science, 60 Lenina ave., Kharkiv 61001, Ukraine

,

Igor V. Komarov

^bEnamine Ltd., Vul. Oleksandra Matrosova 23, 01103 Kyiv, Ukraine Email: Pavel.Mykhailiuk@gmail.com

^cDepartment of Chemistry, and Kyiv National Taras Shevchenko University, Vul. Volodymyrska 64, Kyiv 01033, Ukraine

,

Pavel K. Mykhailiuk*

^bEnamine Ltd., Vul. Oleksandra Matrosova 23, 01103 Kyiv, Ukraine Email: Pavel.Mykhailiuk@gmail.com

^cDepartment of Chemistry, and Kyiv National Taras Shevchenko University, Vul. Volodymyrska 64, Kyiv 01033, Ukraine

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Abstract

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Abstract

Two isomeric conformationally restricted analogues of 4-trifluoromethylpiperidine were designed. The synthesis was performed in four steps from commercially available N-benzylmaleimide. The key reaction was the [3+2] cycloaddition between trifluoromethyldiazomethane and N-benzylmaleimide.

Key words

amines - trifluoromethyl group - cyclopropane - 4-trifluoromethylpiperidine - drug design

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References

References
1 Wishart DS, Knox C, Guo AC, Cheng D, Shrivastaya S, Tzur D, Gautam B, Hassanali M. Nucleic Acids Res. 2008; 36 (database issue): D.901
2 Roughley SD, Jordan AM. J. Med. Chem. 2011; 54: 3451

For some recent examples, see:

3a Sparey T, Beher D, Best J, Biba M, Castro JL, Clarke E, Hannam J, Harrison T, Lewis H, Madin A, Shearman M, Sohal B, Tsou N, Welch C, Wrigley J. Bioorg. Med. Chem. Lett. 2005; 15: 4212
3b Xin Z, Peng H, Zhang A, Talreja T, Kumaravel G, Xu L, Rohde E, Jung M, Shackett MN, Kocisko D, Chollate S, Dunah AW, Snodgrass-Belt PA, Arnold HM, Taveras AG, Rhodes KJ, Scannevin RH. Bioorg. Med. Chem. Lett. 2011; 21: 7277
3c Micheli F, Holmes I, Arista L, Bonanomi G, Braggio S, Cardullo F, Fabio RD, Donati D, Gentile G, Hamprecht D, Terreni S, Heidbreder C, Savoia C, Griffante C, Worby A. Bioorg. Med. Chem. Lett. 2009; 19: 4011
3d Lange JH. M, Neut MA.W, Hartog AP, Wals HC, Hoogendoorn J, Stuivenberg HH, Vliet BJ, Kruse CG. Bioorg. Med. Chem. Lett. 2010; 20: 1752
3e Keith JM, Gomez LA, Letavic MA, Ly KS, Jablonowski JA, Seierstad M, Barbier AJ, Wilson SJ, Boggs JD, Fraser IC, Mazur C, Lovenberg TW, Carruthers NI. Bioorg. Med. Chem. Lett. 2007; 17: 702
3f Provins L, Christophe B, Danhaive P, Dulieu J, Durieu V, Gillard M, Lebon F, Lengelé S, Quéré L, Keulen B. Bioorg. Med. Chem. Lett. 2006; 16: 1834
3g Bennacef I, Salinas CA, Bonasera TA, Gunn RN, Audrain H, Jakobsen S, Nabulsi N, Weinzimmer D, Carson RE, Huang Y, Holmes I, Micheli F, Heidbreder C, Gentile G, Rossi T, Laruelle M. Bioorg. Med. Chem. Lett. 2009; 19: 5056
3h Kerekes AD, Esposite SJ, Doll RJ, Tagat JR, Yu T, Xiao Y, Zhang Y, Prelusky DB, Tevar S, Gray K, Terracina GA, Lee S, Jones J, Liu M, Basso AD, Smith EB. J. Med. Chem. 2011; 54: 201
3i Woods JR, Mo H, Bieberich AA, Alavanja T, Colby DA. J. Med. Chem. 2011; 54: 7933

4 The search was performed in July 2012 in ‘Reaxys’ database.
5 The search was performed in February 2011 in ‘MDL Drug data report’ database.

For some recent reviews on this topic, see:

6a Kirk KL. Org. Proc. Res. Dev. 2008; 12: 305
6b Filler R, Saha R. Future Med. Chem. 2009; 1: 777
6c Purser S, Moore PR, Swallow S, Gouverneur V. Chem. Soc. Rev. 2008; 37: 320
6d Hagmann WK. J. Med. Chem. 2008; 51: 4359
6e Böhm H.-J, Banner D, Bendels S, Kansy M, Kuhn B, Müller K, Obst-Sander U, Stahl M. ChemBioChem 2004; 5: 637

7a Bohm HJ. Prediction of non-bonded interactions in drug design. In Protein-Ligand Interactions. Bohm HJ, Schneider G. Wiley-VCH; Weinheim: 2003: 3
7b Schaeffer L. The role of functional groups in drug-receptor interactions. In The Practice of Medicinal Chemistry. 3rd ed., Wermuth CG. Academic Press/Elsevier; Amsterdam: 2008: 464

8a Mann A. Conformational restriction and/or steric hindrance in medicinal chemistry. In The Practice of Medicinal Chemistry. 3rd ed., Wermuth CG. Academic Press/Elsevier; Amsterdam: 2008: 363
8b Martin SF. Pure Appl. Chem. 2007; 79: 193
8c Cowell SM, Lee YS, Cain JP, Hruby VJ. Curr. Med. Chem. 2004; 11: 2785
8d Harrold MW. Am. J. Pharm. Educ. 1996; 60: 192

Some recent papers:

9a Renslo AR, Jaishankar P, Venkatachalam R, Hackbarth C, Lopez S, Patel DV, Gordeev MF. J. Med. Chem. 2005; 48: 5009
9b Biagetti M, Leslie CP, Mazzali A, Seri C, Pizzi DA, Bentley J, Genski T, Fabio RD, Zonzini L, Caberlotto L. Bioorg. Med. Chem. Lett. 2010; 20: 4741
9c Lunn G, Roberts LR, Content S, Critcher DJ, Douglas S, Fenwick AE, Gethin DM, Goodwin G, Greenway D, Greenwood S, Hall K, Thomas M, Thompson S, Williams D, Wood G, Wylie A. Bioorg. Med. Chem. Lett. 2012; 22: 2200
9d Lunn G, Banks BJ, Crook R, Feeder N, Pettman A, Sabnis Y. Bioorg. Med. Chem. Lett. 2011; 21: 4608
9e Blizzard TA, DiNinno F, Morgan JD, Chen HY, Wu JY, Gude C, Kim S, Chan W, Birzin ET, Yang YT, Pai L.-Y, Zhang Z, Hayes EC, DaSilva CA, Tang W, Rohrer SP, Schaeffer JM, Hammond ML. Bioorg. Med. Chem. Lett. 2004; 14: 3861
9f Blizzard TA, DiNinno F, Morgan JD, Chen HY, Wu JY, Kim S, Chan W, Birzin ET, Yang YT, Pai L.-Y, Fitzgerald PM. D, Sharma N, Li Y, Zhang Z, Hayes EC, DaSilva CA, Tang W, Rohrer SP, Schaeffer JM, Hammond ML. Bioorg. Med. Chem. Lett. 2005; 15: 107
9g Simpkins LM, Bolton S, Pi Z, Sutton JC, Kwon C, Zhao G, Magnin DR, Augeri DJ, Gungor T, Rotella DP, Sun Z, Liu Y, Slusarchyk WS, Marcinkeviciene J, Robertson JG, Wang A, Robl JA, Atwal KS, Zahler RL, Parker RA, Kirby MS, Hamann LG. Bioorg. Med. Chem. Lett. 2007; 17: 6476
9h Kaur K, Aeron S, Bruhaspathy M, Shetty SJ, Gupta S, Hegde LH, Silamkoti AD.V, Mehta A, Chugh A, Gupta JB, Sarma PK. S, Kumar N. Bioorg. Med. Chem. Lett. 2005; 15: 2093

10 Gootz TD, Zaniewski R, Haskell S, Schmieder B, Tankovic J, Girard D, Courvalin P, Polzer RJ. Antimicrob. Agents Chemother. 2006; 40: 2691

11a Artamonov OS, Mykhailiuk PK, Voievoda NM, Volochnyuk DM, Komarov IV. Synthesis 2010; 443
11b Atherton JH, Fields R. J. Chem. Soc. C 1968; 1507

12 Review on trifluoromethylcyclopropanes: Grygorenko OO, Artamonov OS, Komarov IV, Mykhailiuk PK. Tetrahedron 2011; 67: 803

Selected papers on trifluoromethylcyclopropanes:

13a Risse J, Fernandez-Zumel MA, Cudre Y, Severin K. Org. Lett. 2012; 14: 3060
13b Wen L, Zhang H, Lin H, Shen Q, Lu L. J. Fluorine Chem. 2012; 133: 171
13c Petrov VA, Marshall W. J. Fluorine Chem. 2012; 133: 61
13d Yarmolchuk VS, Bezdudny AV, Tolmacheva NA, Lukin O, Boyko AN, Chekotylo A, Tolmachev AA, Mykhailiuk PK. Synthesis 2012; 44: 1152
13e Lin H, Shen Q, Lu L. J. Org. Chem. 2011; 76: 7359
13f Bezdudny AV, Klukovsky D, Simurova N, Mykhailiuk PK, Shishkin OV, Pustovit YM. Synthesis 2011; 119
13g Wan W, Gao Y, Jiang H, Hao J. J. Fluorine Chem. 2008; 129: 510
13h Denton JR, Sukumaran D, Davies HM. L. Org. Lett. 2007; 9: 2625
13i Titanyuk ID, Beletskaya IP, Peregudov AS, Osipov SN. J. Fluorine Chem. 2007; 128: 723
13j Wang Y, Zhao X, Li Y, Lu L. Tetrahedron Lett. 2004; 45: 7775
13k Ghanem A, Lacrampe F, Aboul-Enein HY, Schurig V. Monatsh. Chem. 2005; 136: 1205
13l Muller P, Grass S, Shahi SP, Bernardinelli G. Tetrahedron 2004; 60: 4755
13m Jiang B, Zhang F, Xiong W. Chem. Commun. 2003; 536
13n Katagiri T, Yamaji S, Handa M, Irie M, Uneyama K. Chem. Commun. 2001; 2054
13o Katagiri T, Irie M, Uneyama K. Org. Lett. 2000; 2: 2423
13p Dmowski W, Wolniewicz A. J. Fluorine Chem. 2000; 102: 141
13q Katagiri T, Irie M, Uneyama K. Tetrahedron: Asymmetry 1999; 10: 2583
13r Bouilon J.-P, Janousek Z, Viehe HG, Tinant B, Declercq J.-P. J. Chem. Soc., Perkin Trans. 1 1996; 1853
13s Huisgen R, Mloston G. Tetrahedron Lett. 1989; 30: 7041
13t O’Bannon PE. O, Dailey WP. Tetrahedron Lett. 1989; 30: 4197

For trifluoromethylcyclopropanes obtained by metal-catalyzed trifluoromethylcyclopropanation of alkenes by CF₃CHN₂, see:

14a Le MauxP, Juillard S, Simonneaux G. Synthesis 2006; 1701
14b Mykhailiuk PK, Afonin S, Ulrich AS, Komarov IV. Synthesis 2008; 1757
14c Mykhailiuk PK, Afonin S, Palamarchuk GV, Shishkin OV, Ulrich AS, Komarov IV. Angew. Chem. Int. Ed. 2008; 47: 5765
14d Morandi B, Carreira EM. Angew. Chem. Int. Ed. 2010; 49: 938
14e Duncton MA. J, Ayala L, Kaub C, Janagani S, Edwards WT, Orike N, Ramamoorthy K, Kincaid J, Kelly MG. Tetrahedron Lett. 2010; 51: 1009
14f Villar IS, Gradillas A, Perez-Castells J. Eur. J. Org. Chem. 2010; 5850
14g Morandi B, Mariampillai B, Carreira EM. Angew. Chem. Int. Ed. 2011; 50: 1101
14h Morandi B, Cheang J, Carreira EM. Org. Lett. 2011; 13: 3080

15 Gilman H, Jones LG. J. Am. Chem. Soc. 1943; 65: 1458

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