Synthesis of Cyclopropyl- and Cyclobutylpiperidines: Advanced Building Blocks for Drug Discovery

Ivan I. Vyzir; Rustam T. Iminov; Anton Tverdokhlebov; Andrey A. Tolmachev; Andriy V. Shcherbatiuk; Pavel K. Mykhailiuk; Angelina V. Biitseva

doi:10.1055/s-0035-1560199

Synthesis, Table of Contents

Synthesis 2015; 47(24): 3963-3971
DOI: 10.1055/s-0035-1560199

paper

Synthesis of Cyclopropyl- and Cyclobutylpiperidines: Advanced Building Blocks for Drug Discovery

Authors

Ivan I. Vyzir

^aEnamine Ltd., 78 Chervonotkatska str., 02094, Kyiv, Ukraine Email: A.tverdohlebov@mail.enamine.net Email: Pavel.Mykhailiuk@mail.enamine.net Email: Pavel.Mykhailiuk@gmail.com

^bNational Technical University of Ukraine ‘Kyiv Polytechnic Institute’, 37 Peremohy ave., 03056, Kyiv, Ukraine
Rustam T. Iminov

^aEnamine Ltd., 78 Chervonotkatska str., 02094, Kyiv, Ukraine Email: A.tverdohlebov@mail.enamine.net Email: Pavel.Mykhailiuk@mail.enamine.net Email: Pavel.Mykhailiuk@gmail.com
Anton Tverdokhlebov*

^aEnamine Ltd., 78 Chervonotkatska str., 02094, Kyiv, Ukraine Email: A.tverdohlebov@mail.enamine.net Email: Pavel.Mykhailiuk@mail.enamine.net Email: Pavel.Mykhailiuk@gmail.com
Andrey A. Tolmachev

^aEnamine Ltd., 78 Chervonotkatska str., 02094, Kyiv, Ukraine Email: A.tverdohlebov@mail.enamine.net Email: Pavel.Mykhailiuk@mail.enamine.net Email: Pavel.Mykhailiuk@gmail.com

^cTaras Shevchenko National University of Kyiv, 64/13 Volodymyrska str., 01601, Kyiv, Ukraine
Andriy V. Shcherbatiuk

^aEnamine Ltd., 78 Chervonotkatska str., 02094, Kyiv, Ukraine Email: A.tverdohlebov@mail.enamine.net Email: Pavel.Mykhailiuk@mail.enamine.net Email: Pavel.Mykhailiuk@gmail.com

^cTaras Shevchenko National University of Kyiv, 64/13 Volodymyrska str., 01601, Kyiv, Ukraine
Pavel K. Mykhailiuk*

^aEnamine Ltd., 78 Chervonotkatska str., 02094, Kyiv, Ukraine Email: A.tverdohlebov@mail.enamine.net Email: Pavel.Mykhailiuk@mail.enamine.net Email: Pavel.Mykhailiuk@gmail.com

^cTaras Shevchenko National University of Kyiv, 64/13 Volodymyrska str., 01601, Kyiv, Ukraine
Angelina V. Biitseva

^cTaras Shevchenko National University of Kyiv, 64/13 Volodymyrska str., 01601, Kyiv, Ukraine

Abstract

All articles of this category

Dedicated to the 25th anniversary of Enamine Ltd.

Abstract

A library of cyclopropyl- and cyclobutylpiperidine derivatives were synthesized from commonly available starting materials through Wittig reactions.

Key words

amines - azetidines - piperidines - phosphonium salts - Wittig reaction

Full Text

References

References
1 Rubiralta M, Giralt E, Diez A. Piperidine: Structure, Preparation, Reactivity and Synthetic Applications of Piperidine and its Derivatives. Elsevier; Amsterdam: 1991
2 Watson PS, Jiang B, Scott B. Org. Lett. 2000; 2: 3679

3a Weintraub PM, Sabol JS, Kane JM, Borcherding DR. Tetrahedron 2003; 59: 2953
3b Laschat S, Dickner T. Synthesis 2000; 1781
3c Merino P, Tejero T, Greco G, Marca E, Delso I, Gómez-SanJuan A, Matute R. Heterocycles 2011; 84: 75
3d Felpin F.-X, Lebreton J. Eur. J. Org. Chem. 2003; 3693
3e Buffat MG. P. Tetrahedron 2004; 60: 1701

4a Källström S, Leino R. Bioorg. Med. Chem. 2008; 16: 601
4b Berardi F, Abate C, Ferorelli S, Colabufo NA, Perrone R. Centr. Nerv. Syst. Agents Med. Chem. 2009; 9: 205

5 Röhricht F, Gadhia S, Alam R, Willis M. Sci. World J. 2012; 512047 ; doi: 10.1100/2012/512047

6a Makovec F, Revel L, Letari O, Mennuni L, Impicciatore M. Eur. J. Pharmacol. 1999; 369: 81
6b Scarpignato C, Pelosini I, Di Mario F. Dig. Dis. Sci. 2006; 24: 11
6c Graul A, Mealy N, Bayés M. Drugs Future 2003; 28: 797

7a Lovell PJ, Bromidge SM, Dabbs S, Duckworth DM, Forbes IT, Jennings AJ, King FD, Middlemiss DN, Rahman SK, Saunders DV, Collin LL, Hagan JJ, Riley GJ, Thomas DR. J. Med. Chem. 2000; 43: 342
7b Mahé C, Loetscher E, Feuerbach D, Müller W, Seiler MP, Schoeffter P. Eur. J. Pharmacol. 2004; 495: 97

8a Aslanian RG, Berlin MY, Huang Y, McCormick KD, Mutahi MW, Shin N.-Y, Ting P, Tom WC, Zheng J. US 20070010513, 2007
8b Fernandez MC, Gonzalez-Garcia MR, Liu B, Pfeifer LA. WO 2013112323, 2013
8c Glatthar R, Orain D, Spanka C. WO 2007071358, 2007

9a Matsuda T, Tsuboi T, Murakami M. J. Am. Chem. Soc. 2007; 129: 12596
9b Wang B, Shen Y.-M, Shi Y. J. Org. Chem. 2006; 71: 9519
9c Jiang M, Liu L.-P, Shi M, Li Y. Org. Lett. 2010; 12: 116
9d de Meijere A, Becker H, Stolle A, Kozhushkov SI, Bes MT, Salaün J, Noltemeyer M. Chem. Eur. J. 2005; 11: 2471
9e Utimoto K, Tamura M, Sisido K. Tetrahedron 1973; 29: 1169
9f Zhou H, Huang X, Chen W. Synlett 2003; 2080
9g Li S, Luo Y, Wu J. Org. Lett. 2011; 13: 3190
9h Lechevallier A, Huet F, Conia JM. Tetrahedron 1983; 39: 3307
9i Bernard AM, Piras PP. Synth. Commun. 1997; 27: 709
9j Rousseau G, le Perchec P, Conia JM. Tetrahedron 1976; 32: 2533

10a de Meijere A, Wenck H, Zöllner S, Merstetter P, Arnold A, Gerson F, Schreiner PR, Boese R, Bläser D, Gleiter R, Kozhushkov SI. Chem. Eur. J. 2001; 7: 5382
10b Bräse S, Wertal H, Frank D, Vidović D, de Meijere A. Eur. J. Org. Chem. 2005; 4167
10c Widjaja T, Fitjer L, Pal A, Schmidt H.-G, Noltemeyer M, Diedrich C, Grimme S. J. Org. Chem. 2007; 72: 9264
10d Meyer-Wilmes I, Gerke R, Fitjer L. Tetrahedron 2009; 65: 1689
10e Fitjer L, Majewski M, Monzó-Oltra H. Tetrahedron 1995; 51: 8835

11a Qiu Y.-L, Wang C, Cao H, Peng X, Tang D, Or YS. US 2011300104, 2011
11b Lechevallier A, Huet F, Conia JM. Tetrahedron 1983; 39: 3317
11c Taber DF, Tian W. J. Org. Chem. 2008; 73: 7560
11d von Seebach M, Kozhushkov SI, Schill H, Frank D, Boese R, Benet-Buchholz J, Yufit DS, de Meijere A. Chem. Eur. J. 2007; 13: 167

12a Löhr S, Jacobi C, Johann A, Gottschalk G, de Meijere A. Eur. J. Org. Chem. 2000; 2979
12b Lillo VJ, Gomez C, Yus M. ARKIVOC 2010; (iii): 29
12c Loehr S, de Meijere A. Synlett 2001; 489
12d Miyazawa K, Löhr S, de Meijere A. Mol. Cryst. Liq. Cryst. Sci. Technol., Sect. A 2002; 373: 83

13a Behrens C, Christensen IT, Lau J, Ling A, Luntd BF, Madsen P, Plewe MB, Sams C, Sidelmann UG, Thogersen H, Truesdale LK, Vagner J. EP 1183229, 2005
13b Jorgenson MJ. J. Am. Chem. Soc. 1969; 91: 6432
13c O’Dowd H, Lewis JG, Trias J, Asano R, Blais J, Lopez SL, Park CK, Wu C, Wang W, Gordeev MF. Bioorg. Med. Chem. Lett. 2008; 18: 2645

14 The Wittig reaction of N-(tert-butoxycarbonyl)pyrrolidin-2-one failed with 3a,b due to the high activity of the NCH₂C(O) group, which enolizes easily in the presence of a base.

15a Maercker A, Daub VE. E. Tetrahedron 1994; 50: 2439
15b van den Heuvel CJ. M, Hofland A, van Velzen JC, Steinberg H, de Boer TJ. Recl. Trav. Chim. Pays-Bas 1984; 103: 233
15c de Meijere A, von Seebach M, Kozhushkov SI, Boese R, Blaeser D, Cicchi S, Dimoulas T, Brandi A. Eur. J. Org. Chem. 2001; 3789

16a Fitjer L, Quabeck U. Synthesis 1987; 299
16b Krapcho AP, Jahngen EG. E. J. Org. Chem. 1974; 39: 1650

For our ongoing interest in unique secondary amines, see:

17a Kubyshkin V, Kheylik Y, Mykhailiuk PK. J. Fluorine Chem. 2015; 175: 73
17b Druzhenko T, Denisenko O, Kheylik Y, Zozulya S, Shishkina SS, Tolmachev A, Mykhailiuk PK. Org. Lett. 2015; 17: 1922
17c Artamonov OS, Slobodyanyuk EY, Volochnyuk DM, Komarov IV, Tolmachev AA, Mykhailiuk PK. Eur. J. Org. Chem. 2014; 3592
17d Yarmolchuk VS, Shishkin OV, Starova VS, Zaporozhets OA, Kravchuk O, Zozulya S, Komarov IV, Mykhailiuk PK. Eur. J. Org. Chem. 2013; 3086
17e Artamonov OS, Slobodyanyuk EY, Shishkin OV, Komarov IV, Mykhailiuk PK. Synthesis 2013; 45: 225
17f Shcherbatiuk AV, Shyshlyk OS, Yarmoliuk DV, Shishkin OV, Shishkina SV, Starova VS, Zaporozhets OA, Zozulya S, Moriev R, Kravchuk O, Manoilenko O, Tolmachev AA, Mykhailiuk PK. Tetrahedron 2013; 69: 3796

18a Hercouet A, Le Corre M. Tetrahedron 1981; 37: 2861
18b Schmidbaur H, Schier A, Neugebauer D. Chem. Ber. 1983; 116: 2173
18c Corey EJ, Desai MC. Tetrahedron Lett. 1985; 26: 5747

Supplementary Material

Supporting Information (PDF) (opens in new window)