research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890

Crystal structure of (1S,4S)-2,5-diazo­niabi­cyclo[2.2.1]heptane dibromide

CROSSMARK_Color_square_no_text.svg

aDepartment of Crystallography, Saint-Petersburg State University, Universitetskaya Nab. 7/9, 199034 St. Petersburg, Russian Federation, and bDepartment of Genetics and Biotechnology, Saint-Petersburg State University, Universitetskaya Nab. 7/9, 199034 St. Petersburg, Russian Federation
*Correspondence e-mail: sergei.britvin@spbu.ru

Edited by A. J. Lough, University of Toronto, Canada (Received 16 October 2017; accepted 31 October 2017; online 17 November 2017)

The cage of 2,5-di­aza­bicyclo­[2.2.1]heptane is frequently employed in synthetic chemistry as a rigid bicyclic counterpart of the piperazine ring. The 2,5-di­azabicyclo­[2.2.1]heptane scaffold is incorporated into a variety of compounds having pharmacological and catalytic applications. The unsubstituted parent ring of the system, 2,5-di­aza­bicyclo­[2.2.1]heptane itself, has not been structurally characterized. We herein report on the mol­ecular structure of the parent ring in (1S,4S)-2,5-diazo­niabi­cyclo­[2.2.1]heptane dibromide, C5H12N22+·2Br. The asymmetric unit contains two crystallographically independent cages of 2,5-di­aza­bicyclo­[2.2.1]heptane. Each cage is protonated at the two nitro­gen sites. The overall charge balance is maintained by four crystallographically independent bromide ions. In the crystal, the components of the structure are linked via a complex three-dimensional network of N—H⋯Br hydrogen bonds.

1. Chemical context

Derivatives of the bicyclic nucleus of 2,5-di­aza­bicyclo­[2.2.1]heptane comprise a wide family of biochemically active compounds (Murineddu et al., 2012[Murineddu, G., Asproni, B., Pinna, G., Curzu, M. M., Dore, A., Pau, A., Deligia, F. & Pinna, G. A. (2012). Curr. Med. Chem. 19, 5342-5363.]), including anti­biotics (McGuirk et al., 1992[McGuirk, P. R., Jefson, M. R., Mann, D. D., Elliott, N. C., Chang, P., Cisek, E. P., Cornell, C. P., Gootz, T. D., Haskell, S. L., Hindahl, M. S., LaFleur, L. J., Rosenfeld, M. J., Shryock, T. R., Silvia, A. M. & Weber, F. H. (1992). J. Med. Chem. 35, 611-620.]; Remuzon et al., 1993[Remuzon, P., Bouzard, D., Clemencin, C., Dussy, C., Jacquet, J. P., Fung-Tome, J. & Kessler, R. E. (1993). Eur. J. Med. Chem. 28, 455-461.]), vasodilating (López-Ortiz et al., 2014[López-Ortiz, M., Monsalvo, I., Demare, P., Paredes, C., Mascher, D., Hernández, C., Hernández, M. & Regla, I. (2014). Chem. Biol. Drug Des. 83, 710-720.]) and anti­tumor agents (Hamblett et al., 2007[Hamblett, C. L., Methot, J. L., Mampreian, D. M., Sloman, D. L., Stanton, M. G., Kral, A. M., Fleming, J. C., Cruz, J. C., Chenard, M., Ozerova, N., Hitz, A. M., Wang, H., Deshmukh, S. V., Nazef, N., Harsch, A., Hughes, B., Dahlberg, W. K., Szewczak, A. A., Middleton, R. E., Mosley, R. T., Secrist, J. P. & Miller, T. A. (2007). Bioorg. Med. Chem. Lett. 17, 5300-5309.]; Shchekotikhin et al., 2014[Shchekotikhin, A. E., Glazunova, V. A., Dezhenkova, L. G., Luzikov, Y. N., Buyanov, V. N., Treshalina, H. M., Lesnaya, N. A., Romanenko, V. I., Kaluzhny, D. N., Balzarini, J., Agama, K., Pommier, Y., Shtil, A. A. & Preobrazhenskaya, M. N. (2014). Eur. J. Med. Chem. 86, 797-805.]; Gerstenberger et al., 2016[Gerstenberger, B. S., Trzupek, J. D., Tallant, C., Fedorov, O., Filippakopoulos, P., Brennan, P. E., Fedele, V., Martin, S., Picaud, S., Rogers, C., Parikh, M., Taylor, A., Samas, B., O'Mahony, A., Berg, E., Pallares, G., Torrey, A. D., Treiber, D. K., Samardjiev, I. J., Nasipak, B. T., Padilla-Benavides, T., Wu, Q., Imbalzano, A. N., Nickerson, J. A., Bunnage, M. E., Müller, S., Knapp, S. & Owen, D. R. (2016). J. Med. Chem. 59, 4800-4811.]; Laskar et al., 2017[Laskar, S., Sánchez-Sánchez, L., López-Ortiz, M., López-Muñoz, H., Escobar-Sánchez, M. L., Sánchez, A. T. & Regla, I. (2017). J. Enzyme Inhib. Med. Chem. 32, 1129-1135.]). A broad range of these compounds have been found to exhibit potency as nicotinic acetyl­choline receptor ligands (Toma et al., 2002[Toma, L., Quadrelli, P., Bunnelle, W. H., Anderson, D. J., Meyer, M. D., Cignarella, G., Gelain, A. & Barlocco, D. (2002). J. Med. Chem. 45, 4011-4017.]; Artali et al., 2005[Artali, R., Bombieri, G. & Meneghetti, F. (2005). Farmaco, 60, 313-320.]; Bunnelle et al., 2007[Bunnelle, W. H., Daanen, J. F., Ryther, K. B., Schrimpf, M. R., Dart, M. J., Gelain, A., Meyer, M. D., Frost, J. M., Anderson, D. J., Buckley, M., Curzon, P., Cao, Y.-J., Puttfarcken, P., Searle, X., Ji, J., Putman, C. B., Surowy, C., Toma, L. & Barlocco, D. (2007). J. Med. Chem. 50, 3627-3644.]; Anderson et al., 2008[Anderson, D. J., Bunnelle, W., Surber, B., Du, J., Surowy, C., Tribollet, E., Marguerat, A., Bertrand, D. & Gopalakrishnan, M. (2008). J. Pharmacol. Exp. Ther. 324, 179-187.]; Li et al., 2010[Li, T., Bunnelle, W. H., Ryther, K. B., Anderson, D. J., Malysz, J., Helfrich, R., Grønlien, J. H., Håkerud, M., Peters, D., Schrimpf, M. R., Gopalakrishnan, M. & Ji, J. (2010). Bioorg. Med. Chem. Lett. 20, 3636-3639.]; Beinat et al., 2015[Beinat, C., Reekie, T., Banister, S. D., O'Brien-Brown, J., Xie, T., Olson, T. T., Xiao, Y., Harvey, A., O'Connor, S., Coles, C., Grishin, A., Kolesik, P., Tsanaktsidis, J. & Kassiou, M. (2015). Eur. J. Med. Chem. 95, 277-301.]; Bertrand et al., 2015[Bertrand, D., Lee, C.-H. L., Flood, D., Marger, F. & Donnelly-Roberts, D. (2015). Pharmacol. Rev. 67, 1025-1073.]). As a result of the occurrence of two chiral centers, 2,5-di­aza­bicyclo­[2.2.1]hepta­nes are utilized as chiral scaffolds in asymmetric catalysis (Jordis et al., 1999[Jordis, U., Kesselgruber, M., Nerdinger, S. & Mereiter, K. (1999). Mendeleev Commun. 9, 147-148.]; González-Olvera et al., 2008[González-Olvera, R., Demare, P., Regla, I. & Juaristi, E. (2008). Arkivoc, 6, 61-72.]; Castillo et al., 2013[Castillo, I., Pérez, V., Monsalvo, I., Demare, P. & Regla, I. (2013). Inorg. Chem. Commun. 38, 1-4.]; Díaz-de-Villegas et al., 2014[Díaz-de-Villegas, M. D., Gálvez, J. A., Badorrey, R. & López-Ram-de-Víu, P. (2014). Adv. Synth. Catal. 356, 3261-3288.]; Avila-Ortiz et al., 2015[Avila-Ortiz, C. G., Lopez-Ortiz, M., Vega-Penaloza, A., Regla, I. & Juaristi, E. (2015). Asymm. Catal. 2, 37-44.]). The di­amine system of 2,5-di­aza­bicyclo­[2.2.1]heptane is traditionally included in screening libraries as a rigid counterpart of the flexible piperazine ring (Siebeneicher et al., 2016[Siebeneicher, H., Bauser, M., Buchmann, B., Heisler, I., Müller, T., Neuhaus, R., Rehwinkel, H., Telser, J. & Zorn, L. (2016). Bioorg. Med. Chem. Lett. 26, 1732-1737.]; Dam et al., 2016[Dam, J. H., Bender, D., Peters, D. & Någren, K. (2016). Nucl. Med. Biol. 43, 42-51.]; Cernak et al., 2017[Cernak, T., Gesmundo, N. J., Dykstra, K., Yu, Y., Wu, Z., Shi, Z.-C., Vachal, P., Sperbeck, D., He, S., Murphy, B. A., Sonatore, L., Williams, S., Madeira, M., Verras, A., Reiter, M., Lee, C. H., Cuff, J., Sherer, E. C., Kuethe, J., Goble, S., Perrotto, N., Pinto, S., Shen, D.-M., Nargund, R., Balkovec, J., DeVita, R. J. & Dreher, S. D. (2017). J. Med. Chem. 60, 3594-3605.]; Llona-Minguez et al., 2017[Llona-Minguez, S., Höglund, A., Ghassemian, A., Desroses, M., Calderón-Montaño, J. M., Burgos Morón, E., Valerie, N. C. K., Wiita, E., Almlöf, I., Koolmeister, T., Mateus, A., Cazares-Körner, C., Sanjiv, K., Homan, E., Loseva, O., Baranczewski, P., Darabi, M., Mehdizadeh, A., Fayezi, S., Jemth, A.-S., Warpman Berglund, U., Sigmundsson, K., Lundbäck, T., Jenmalm Jensen, A., Artursson, P., Scobie, M. & Helleday, T. (2017). J. Med. Chem. 60, 4279-4292.]; Wei et al., 2017[Wei, M., Zhang, X., Wang, X., Song, Z., Ding, J., Meng, L.-H. & Zhang, A. (2017). Eur. J. Med. Chem. 125, 1156-1171.]). As a consequence, numerous synthetic routes for the preparation of 2,5-di­aza­bicyclo­[2.2.1]heptane derivatives have been introduced (see: Portoghese & Mikhail, 1966[Portoghese, P. S. & Mikhail, A. A. (1966). J. Org. Chem. 31, 1059-1062.]; Jordis et al., 1990[Jordis, U., Sauter, F., Siddiqi, S. M., Küenburg, B. & Bhattacharya, K. (1990). Synthesis, pp. 925-930.]; Yakovlev et al., 2000[Yakovlev, M. E., Lobanov, P. S. & Potekhin, A. A. (2000). Chem. Heterocycl. Compd, 36, 429-431.]; Fiorelli et al., 2005[Fiorelli, C., Marchioro, C., Martelli, G., Monari, M. & Savoia, D. (2005). Eur. J. Org. Chem. 2005, 3987-3993.]; Beinat et al., 2013[Beinat, C., Banister, S. D., McErlean, C. S. P. & Kassiou, M. (2013). Tetrahedron Lett. 54, 5345-5347.]; Cui et al., 2015[Cui, B., Yu, J., Yu, F.-C., Li, Y.-M., Chang, K.-J. & Shen, Y. (2015). RSC Adv. 5, 10386-10392.]; Choi et al., 2016[Choi, C., Nuhant, P., Mousseau, J. J., Yang, X., Gerstenberger, B. S., Williams, J. M. & Wright, S. W. (2016). Org. Lett. 18, 5748-5751.] and the references cited therein). At the same time, the reported structural data on 2,5-di­aza­bicyclo­[2.2.1]heptane derivatives are surprisingly scarce (see the Database survey). Moreover, the parent ring of unsubstituted 2,5-di­aza­bicyclo[2.2.1]heptane has not been structurally characterized. In the framework of current research on caged heterocyclic systems (Britvin & Lotnyk, 2015[Britvin, S. N. & Lotnyk, A. (2015). J. Am. Chem. Soc. 137, 5526-5535.]; Britvin et al., 2016[Britvin, S. N., Rumyantsev, A. M., Zobnina, A. E. & Padkina, M. V. (2016). Chem. Eur. J. 22, 14227-14235.]; 2017a[Britvin, S. N., Rumyantsev, A. M., Silyutina, A. A. & Padkina, M. V. (2017a). ChemistrySelect, 2, 8721-8725.],b[Britvin, S. N., Rumyantsev, A. M., Zobnina, A. E. & Padkina, M. V. (2017b). J. Mol. Struct. 1130, 395-399.]; Britvin & Rumyantsev, 2017b[Britvin, S. N. & Rumyantsev, A. M. (2017b). Acta Cryst. E73, 1712-1715.]), we herein describe the mol­ecular structure of 2,5-di­aza­bicyclo­[2.2.1]heptane (Fig. 1[link]) in its di­hydro­bromide salt, (1S,4S)-2,5-diazo­niabi­cyclo­[2.2.1]heptane di­bro­mide (1).

[Scheme 1]
[Figure 1]
Figure 1
Two views of the diprotonated 2,5-di­aza­bicyclo­[2.2.1]heptane parent ring in 1 (in one of the two independent mol­ecules in the asymmetric unit). The atomic numbering scheme is according to IUPAC notation. Displacement ellipsoids are drawn at the 30% probability level. Hydrogen atoms are depicted as fixed-size spheres of arbitrary radius. The bromide counter-ions have been omitted for clarity.

2. Structural commentary

The asymmetric unit of 1 contains two structurally independent cages of 2,5-di­aza­bicyclo­[2.2.1]heptane (Fig. 2[link]). The mol­ecular geometries of the cages are statistically different: the biggest discrepancy, 0.044 Å, is observed for N2⋯N5 [2.868 (3) Å] and N2A⋯N5A [2.912 (3) Å], whereas the distances between the bridgehead C atoms C1⋯C4 [2.220 (4) Å] and C1A⋯C4A [2.226 (4) Å] are statistically the same (see the Supporting information). Therefore, in spite of bridge-imparted rigidity, the hexa­gonal ring of 2,5-di­aza­bicyclo­[2.2.1]heptane can be affected by some geometric distortions. The framework of 2,5-di­aza­bicyclo­[2.2.1]heptane is frequently considered to be the bicyclic counterpart of piperazine where the occurrence of the C1–C7–C4 bridge imparts rigidity to the hexa­gonal ring (Kiely et al., 1991[Kiely, J. S., Hutt, M. P., Culbertson, T. P., Bucsh, R. A., Worth, D. F., Lesheski, L. E., Gogliotti, R. D., Sesnie, J. C., Solomon, M. & Mich, T. F. (1991). J. Med. Chem. 34, 656-663.]; Beinat et al., 2013[Beinat, C., Banister, S. D., McErlean, C. S. P. & Kassiou, M. (2013). Tetrahedron Lett. 54, 5345-5347.]; 2015[Beinat, C., Reekie, T., Banister, S. D., O'Brien-Brown, J., Xie, T., Olson, T. T., Xiao, Y., Harvey, A., O'Connor, S., Coles, C., Grishin, A., Kolesik, P., Tsanaktsidis, J. & Kassiou, M. (2015). Eur. J. Med. Chem. 95, 277-301.]). It is worth noting that the bicyclic bridged structure of 2,5-di­aza­bicyclo­[2.2.1]heptane determines the boat conformation of its cage (Fig. 1[link]). Contrary to that, the piperazine ring is flexible and can adopt four different conformations: chair, boat, twist-boat and half-boat, the former being the energetically most favourable (SenGupta et al., 2014[SenGupta, S., Maiti, N., Chadha, R. & Kapoor, S. (2014). Chem. Phys. 436-437, 55-62.]). A comparison of the hexa­gonal rings of 2,5-di­aza­bicyclo­[2.2.1]heptane and the chair conformer of piperazine (Fig. 2[link]) shows that the inter­atomic distances between the opposing nitro­gen atoms are remarkably close. The latter feature can be important because the nitro­gen sites are known to be pharmacophores frequently determining the biochemical activity of piperazine derivatives (Patel & Park, 2013[Patel, R. V. & Park, S. W. (2013). Mini Rev. Med. Chem. 13, 1579-1601.]). Therefore, the implication of the 2,5-di­aza­bicyclo­[2.2.1]heptane scaffold as a piperazine analogue in screening libraries looks quite reasonable from the structural point of view.

[Figure 2]
Figure 2
(a) The two independent mol­ecules of 2,5-di­aza­bicyclo­[2.2.1]heptane in the crystal structure of 1 (this work). (b) The chair conformer of piperazine in piperazine-1,4-diium dibromide monohydrate (Bujak, 2015[Bujak, M. (2015). Cryst. Growth Des. 15, 1295-1302.]). The atomic numbering schemes are given in IUPAC notation. Symmetrically equivalent atoms in the piperazine ring are noted in parentheses. Displacement ellipsoids are drawn at the 30% probability level. Hydrogen atoms, bromide counter-ions and water mol­ecules have been omitted for clarity.

3. Supra­molecular features

In the crystal structure of 1, the protonated nitro­gen sites in the two symmetrically non-equivalent 2,5-di­aza­bicyclo­[2.2.1]heptane cages are counter balanced by the four structurally independent bromide ions. This results in the emergence of a complicated network of hydrogen bonds (Fig. 3[link]). Hydrogen-bonded amine mol­ecules are arranged into infinite slabs parallel to (100). The slabs are linked by N—H⋯Br hydrogen bonds into a three-dimensional network. The full listing of N—H⋯Br bonds is given in Table 1[link]. This three-dimensional net of hydrogen bonds is much more complex than the flat `zigzag' hydrogen bonding occurring in the geometrically similar cage of 7-aza­bicyclo­[2.2.1]heptane (7-aza­norbornane) (Britvin & Rumyantsev, 2017a[Britvin, S. N. & Rumyantsev, A. M. (2017a). Acta Cryst. E73, 1385-1388.]).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N2—H2A⋯Br3 0.93 (3) 2.49 (3) 3.358 (2) 156 (2)
N5—H5A⋯Br4 0.92 (3) 2.44 (3) 3.261 (2) 148 (3)
N5—H5B⋯Br1i 0.78 (3) 2.50 (3) 3.242 (2) 161 (3)
N2A—H2AA⋯Br3 0.89 (3) 2.53 (4) 3.344 (2) 152 (3)
N2A—H2AB⋯Br1ii 0.86 (3) 2.48 (3) 3.273 (2) 155 (2)
N5A—H5AA⋯Br2 0.91 (3) 2.42 (3) 3.292 (2) 160 (3)
N5A—H5AB⋯Br1 0.77 (3) 2.77 (3) 3.399 (2) 140 (3)
Symmetry codes: (i) [-x+1, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]; (ii) [-x+1, y+{\script{1\over 2}}, -z+{\script{3\over 2}}].
[Figure 3]
Figure 3
Hydrogen bonding in the crystal structure of 1. Protonated mol­ecules of 2,5-di­aza­bicyclo­[2.2.1]heptane are linked by N—H⋯Br hydrogen bonds, forming slabs parallel to (100). These slabs are linked by N—H⋯Br hydrogen bonds into a three-dimensional network. Displacement ellipsoids are drawn at the 30% probability level. H atoms not involved in hydrogen bonding have been omitted for clarity.

4. Database survey

In spite of extensive studies of 2,5-di­aza­bicyclo­[2.2.1]heptane derivatives (see the Chemical context), there are just 14 structures which comprise this bicyclic system in the Cambridge Structural Database (CSD version 5.38, May 2017; Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]). Jordis et al. (1999[Jordis, U., Kesselgruber, M., Nerdinger, S. & Mereiter, K. (1999). Mendeleev Commun. 9, 147-148.]) reported a series of substituted (1S,4S)-2,5-di­aza­bicyclo­[2.2.1]hepta­nes and provided the first structure determination of the 1,2,5-substituted derivative. Lauteslager et al. (2001[Lauteslager, X. Y., van Stokkum, I. M., van Ramesdonk, H. J., Bebelaar, D., Fraanje, J., Goubitz, K., Schenk, H., Brouwer, A. M. & Verhoeven, J. W. (2001). Eur. J. Org. Chem. pp. 3105-3118.]) carried out a comparative study of chromophores containing piperazine and 2,5-di­aza­bicyclo­[2.2.1]heptane groups. Apart from the majority of the latest studies, which are devoted to different aspects of the organic chemistry of the title scaffold (Alvaro et al., 2007[Alvaro, G., Di Fabio, R., Gualandi, A., Fiorelli, C., Monari, M., Savoia, D. & Zoli, L. (2007). Tetrahedron, 63, 12446-12453.]; Mereiter et al., 2007[Mereiter, K., Skubak, J. & Jordis, U. (2007). Private communication (deposition number 664942). CCDC, Cambridge, England.]; Krasnov et al., 2008[Krasnov, V., Nizova, I. A., Vigorov, A. Yu., Matveeva, T. V., Levit, G. L., Slepukhin, P. A., Ezhikova, M. A. & Kodess, M. I. (2008). Eur. J. Org. Chem. pp. 1802-1810.]; Melgar-Fernández et al., 2008[Melgar-Fernández, R., González-Olvera, R., Olivares-Romero, J. L., González-López, V., Romero-Ponce, L., del Refugio Ramírez-Zárate, M., Demare, P., Regla, I. & Juaristi, E. (2008). Eur. J. Org. Chem. pp. 655-672.]; Wu et al., 2011[Wu, C., Zhang, J., Li, P., Zhang, J. & Wu, J. (2011). Acta Cryst. E67, o272.]), Pérez et al. (2011[Pérez, V., Monsalvo, I., Demare, P., Gómez-Vidales, V., Regla, I. & Castillo, I. (2011). Inorg. Chem. Commun. 14, 389-391.]) and Castillo et al. (2013[Castillo, I., Pérez, V., Monsalvo, I., Demare, P. & Regla, I. (2013). Inorg. Chem. Commun. 38, 1-4.]) have reported the first examples of coordination compounds between copper(II) and substituted 2,5-di­aza­bicyclo­[2.2.1]hepta­nes. To the best of our knowledge, no structural data on the unsubstituted parent ring of 2,5-di­aza­bicyclo­[2.2.1]heptane have been reported.

5. Synthesis and crystallization

(1S,4S)-Di­aza­bicyclo­[2.2.1]heptane di­hydro­bromide (1) was obtained from Sigma–Aldrich and found to be analytically pure [analysis calculated for C5H12Br2N2 (259.97): C 23.10, H 4.65, N 10.78; found C 23.03, H 4.71, N 10.69]. NMR spectra (Bruker Avance 400 spectrometer, using SiMe4 as an external standard) are consistent with the previously published data (Melgar-Fernández et al., 2008[Melgar-Fernández, R., González-Olvera, R., Olivares-Romero, J. L., González-López, V., Romero-Ponce, L., del Refugio Ramírez-Zárate, M., Demare, P., Regla, I. & Juaristi, E. (2008). Eur. J. Org. Chem. pp. 655-672.]) and confirm the purity of the substance (atomic numbering according to Fig. 1[link]): 1H NMR (400.13 MHz, D2O): δ = 4.67 (d, 2H, CH at C1 and C4), 3.65–3.57 (m, 4H, CH2 at C3 and C6), 2.29 (s, 2H, CH2 at C7). 13C{1H} NMR (100.62 MHz, D2O): δ = 56.36 (s, NCHCH2, C1 and C4), 47.09 (s, NCH2CH, C3 and C6), 34.73 (s, CHCH2CH, C7). Crystals of 1 suitable for structural study were obtained by slow evaporation of a saturated aqueous solution at room temperature.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. Hydrogen atoms at nitro­gen sites (i.e. those involved in hydrogen bonding) were freely refined whereas hydrogen atoms at all carbon centers were treated with fixed Uiso(H) = 1.2Ueq(C) and riding coordinates (C—H = 0.97–0.98 Å).

Table 2
Experimental details

Crystal data
Chemical formula C5H12N22+·2Br
Mr 259.99
Crystal system, space group Orthorhombic, P212121
Temperature (K) 100
a, b, c (Å) 9.7298 (6), 11.8643 (5), 14.4933 (7)
V3) 1673.07 (15)
Z 8
Radiation type Mo Kα
μ (mm−1) 9.61
Crystal size (mm) 0.2 × 0.08 × 0.05
 
Data collection
Diffractometer Bruker APEXII CCD
Absorption correction Multi-scan (SADABS; Bruker, 2015[Bruker (2015). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.])
No. of measured, independent and observed [I > 2σ(I)] reflections 15838, 4031, 3959
Rint 0.026
(sin θ/λ)max−1) 0.661
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.014, 0.035, 1.02
No. of reflections 4031
No. of parameters 195
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.53, −0.34
Absolute structure Flack x determined using 1676 quotients [(I+)−(I)]/[(I+)+(I)] (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.])
Absolute structure parameter 0.009 (5)
Computer programs: APEX2 and SAINT (Bruker, 2015[Bruker (2015). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXT (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2014 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]), Mercury (Macrae et al., 2008[Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466-470.]), OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]) and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Supporting information


Computing details top

Data collection: APEX2 (Bruker, 2015); cell refinement: SAINT (Bruker, 2015); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: Mercury (Macrae et al., 2008) and OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: publCIF (Westrip, 2010).

(1S,4S)-2,5-Diazoniabicyclo[2.2.1]heptane dibromide top
Crystal data top
C5H12N22+·2BrDx = 2.064 Mg m3
Mr = 259.99Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121Cell parameters from 9887 reflections
a = 9.7298 (6) Åθ = 2.5–31.5°
b = 11.8643 (5) ŵ = 9.61 mm1
c = 14.4933 (7) ÅT = 100 K
V = 1673.07 (15) Å3Block, colourless
Z = 80.2 × 0.08 × 0.05 mm
F(000) = 1008
Data collection top
Bruker APEXII CCD
diffractometer
4031 independent reflections
Radiation source: fine focus sealed tube3959 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.026
φ and ω scansθmax = 28.0°, θmin = 2.2°
Absorption correction: multi-scan
(SADABS; Bruker, 2015)
h = 1212
k = 1315
15838 measured reflectionsl = 1917
Refinement top
Refinement on F2Hydrogen site location: mixed
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.014 w = 1/[σ2(Fo2) + (0.0162P)2]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.035(Δ/σ)max = 0.001
S = 1.02Δρmax = 0.53 e Å3
4031 reflectionsΔρmin = 0.34 e Å3
195 parametersAbsolute structure: Flack x determined using 1676 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
0 restraintsAbsolute structure parameter: 0.009 (5)
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.5925 (3)0.3998 (2)0.37609 (18)0.0160 (5)
H10.67220.45010.37970.019*
N20.4926 (2)0.4270 (2)0.29906 (15)0.0143 (4)
H2A0.479 (3)0.505 (3)0.2960 (18)0.011 (7)*
H2B0.519 (4)0.403 (3)0.245 (3)0.038 (11)*
C30.3610 (3)0.3669 (2)0.32592 (18)0.0162 (5)
H3A0.33770.30840.28180.019*
H3B0.28480.41920.33100.019*
C40.3987 (3)0.3168 (3)0.41995 (18)0.0183 (6)
H40.32030.29830.45960.022*
N50.4954 (2)0.2198 (2)0.40090 (17)0.0167 (5)
H5A0.454 (3)0.170 (3)0.361 (2)0.024 (9)*
H5B0.504 (3)0.186 (3)0.446 (2)0.013 (8)*
C60.6277 (3)0.2749 (2)0.36993 (18)0.0158 (5)
H6A0.65110.25340.30730.019*
H6B0.70330.25570.41060.019*
C70.4971 (3)0.4045 (2)0.45944 (18)0.0205 (6)
H7A0.45460.47780.46780.025*
H7B0.54110.38020.51610.025*
C1A0.6072 (3)0.8241 (2)0.59473 (17)0.0139 (5)
H1A0.69180.86240.57580.017*
N2A0.4792 (2)0.8628 (2)0.54520 (15)0.0141 (4)
H2AA0.478 (4)0.844 (3)0.486 (2)0.033 (10)*
H2AB0.476 (3)0.935 (3)0.5432 (19)0.010 (7)*
C3A0.3626 (2)0.8184 (2)0.60478 (19)0.0160 (5)
H3AA0.31030.76100.57260.019*
H3AB0.30110.87860.62330.019*
C4A0.4384 (3)0.7687 (2)0.68803 (18)0.0152 (5)
H4A0.38350.76350.74460.018*
N5A0.5014 (2)0.6592 (2)0.65645 (16)0.0154 (4)
H5AA0.437 (3)0.612 (3)0.631 (2)0.019 (8)*
H5AB0.534 (3)0.629 (3)0.698 (2)0.021 (9)*
C6A0.6121 (3)0.6950 (2)0.58809 (17)0.0163 (5)
H6AA0.59070.66940.52620.020*
H6AB0.70150.66620.60590.020*
C7A0.5656 (3)0.8433 (2)0.69531 (17)0.0161 (5)
H7AA0.63280.81490.73890.019*
H7AB0.54390.92140.70870.019*
Br10.52194 (2)0.62674 (2)0.88905 (2)0.01450 (6)
Br20.22116 (2)0.51516 (2)0.60873 (2)0.01567 (6)
Br30.46504 (3)0.70005 (2)0.35710 (2)0.01494 (6)
Br40.26144 (3)0.04454 (2)0.32745 (2)0.01680 (6)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0142 (12)0.0157 (14)0.0181 (13)0.0018 (10)0.0058 (10)0.0015 (10)
N20.0145 (10)0.0138 (12)0.0148 (10)0.0003 (9)0.0011 (8)0.0031 (9)
C30.0109 (11)0.0191 (14)0.0185 (12)0.0006 (10)0.0001 (10)0.0020 (11)
C40.0136 (12)0.0217 (15)0.0195 (12)0.0003 (10)0.0063 (10)0.0044 (11)
N50.0191 (11)0.0135 (12)0.0174 (11)0.0037 (9)0.0026 (9)0.0043 (9)
C60.0125 (11)0.0177 (14)0.0173 (13)0.0002 (10)0.0025 (9)0.0005 (10)
C70.0285 (15)0.0199 (15)0.0130 (12)0.0033 (11)0.0022 (10)0.0030 (10)
C1A0.0107 (11)0.0138 (14)0.0173 (13)0.0008 (9)0.0006 (9)0.0023 (10)
N2A0.0172 (11)0.0115 (12)0.0135 (10)0.0008 (9)0.0007 (8)0.0004 (8)
C3A0.0108 (11)0.0168 (14)0.0206 (13)0.0024 (9)0.0019 (9)0.0010 (11)
C4A0.0143 (12)0.0164 (14)0.0150 (12)0.0014 (10)0.0001 (9)0.0016 (10)
N5A0.0148 (10)0.0141 (11)0.0173 (11)0.0008 (9)0.0031 (8)0.0034 (9)
C6A0.0147 (12)0.0163 (14)0.0178 (12)0.0029 (10)0.0008 (9)0.0006 (10)
C7A0.0173 (12)0.0147 (14)0.0162 (12)0.0020 (10)0.0027 (10)0.0012 (10)
Br10.01665 (12)0.01277 (12)0.01407 (12)0.00094 (9)0.00018 (9)0.00022 (9)
Br20.01471 (12)0.01456 (13)0.01775 (11)0.00228 (9)0.00073 (10)0.00003 (10)
Br30.01588 (12)0.01335 (13)0.01560 (12)0.00039 (9)0.00032 (9)0.00008 (9)
Br40.01390 (12)0.01434 (13)0.02214 (12)0.00278 (9)0.00270 (9)0.00030 (10)
Geometric parameters (Å, º) top
C1—H10.9800C3A—H3AA0.9700
C1—N21.516 (3)C3A—H3AB0.9700
C1—C61.523 (4)C3A—C4A1.532 (4)
C1—C71.525 (4)C4A—H4A0.9800
N2—H2A0.93 (3)C4A—N5A1.508 (3)
N2—H2B0.87 (4)C4A—C7A1.525 (4)
N2—C31.516 (3)N5A—H5AA0.91 (3)
C3—H3A0.9700N5A—H5AB0.77 (3)
C3—H3B0.9700N5A—C6A1.523 (3)
C3—C41.532 (4)C6A—H6AA0.9700
C4—H40.9800C6A—H6AB0.9700
C4—N51.512 (4)C7A—H7AA0.9700
C4—C71.525 (4)C7A—H7AB0.9700
N5—H5A0.92 (3)N2—N52.868 (3)
N5—H5B0.78 (3)N2A—N5A2.912 (3)
N5—C61.512 (3)C1—C42.220 (4)
C6—H6A0.9700C1A—C4A2.226 (4)
C6—H6B0.9700C3—C62.887 (4)
C7—H7A0.9700C3A—C6A2.845 (4)
C7—H7B0.9700N2—C72.340 (4)
C1A—H1A0.9800N2A—C7A2.344 (3)
C1A—N2A1.509 (3)N5—C72.350 (4)
C1A—C6A1.535 (4)N5A—C7A2.340 (4)
C1A—C7A1.530 (3)C3—C72.387 (4)
N2A—H2AA0.89 (3)C3A—C7A2.390 (4)
N2A—H2AB0.86 (3)C6—C72.380 (4)
N2A—C3A1.521 (3)C6A—C7A2.391 (4)
N2—C1—H1114.7N2A—C1A—H1A114.8
N2—C1—C6107.9 (2)N2A—C1A—C6A107.4 (2)
N2—C1—C7100.66 (19)N2A—C1A—C7A101.0 (2)
C6—C1—H1114.7C6A—C1A—H1A114.8
C6—C1—C7102.7 (2)C7A—C1A—H1A114.8
C7—C1—H1114.7C7A—C1A—C6A102.5 (2)
C1—N2—H2A109.5 (17)C1A—N2A—H2AA113 (2)
C1—N2—H2B114 (3)C1A—N2A—H2AB111 (2)
C1—N2—C3104.64 (19)C1A—N2A—C3A103.90 (18)
H2A—N2—H2B109 (3)H2AA—N2A—H2AB102 (3)
C3—N2—H2A111.1 (18)C3A—N2A—H2AA117 (2)
C3—N2—H2B109 (3)C3A—N2A—H2AB110 (2)
N2—C3—H3A111.4N2A—C3A—H3AA111.2
N2—C3—H3B111.4N2A—C3A—H3AB111.2
N2—C3—C4102.0 (2)N2A—C3A—C4A102.76 (19)
H3A—C3—H3B109.2H3AA—C3A—H3AB109.1
C4—C3—H3A111.4C4A—C3A—H3AA111.2
C4—C3—H3B111.4C4A—C3A—H3AB111.2
C3—C4—H4114.9C3A—C4A—H4A114.9
N5—C4—C3106.4 (2)N5A—C4A—C3A106.7 (2)
N5—C4—H4114.9N5A—C4A—H4A114.9
N5—C4—C7101.4 (2)N5A—C4A—C7A101.0 (2)
C7—C4—C3102.7 (2)C7A—C4A—C3A102.9 (2)
C7—C4—H4114.9C7A—C4A—H4A114.9
C4—N5—H5A110 (2)C4A—N5A—H5AA112 (2)
C4—N5—H5B108 (2)C4A—N5A—H5AB109 (3)
C4—N5—C6104.7 (2)C4A—N5A—C6A104.2 (2)
H5A—N5—H5B104 (3)H5AA—N5A—H5AB108 (3)
C6—N5—H5A118 (2)C6A—N5A—H5AA113.2 (19)
C6—N5—H5B113 (2)C6A—N5A—H5AB110 (2)
C1—C6—H6A111.3C1A—C6A—H6AA111.3
C1—C6—H6B111.3C1A—C6A—H6AB111.3
N5—C6—C1102.2 (2)N5A—C6A—C1A102.4 (2)
N5—C6—H6A111.3N5A—C6A—H6AA111.3
N5—C6—H6B111.3N5A—C6A—H6AB111.3
H6A—C6—H6B109.2H6AA—C6A—H6AB109.2
C1—C7—C493.4 (2)C1A—C7A—H7AA113.0
C1—C7—H7A113.0C1A—C7A—H7AB113.0
C1—C7—H7B113.0C4A—C7A—C1A93.6 (2)
C4—C7—H7A113.0C4A—C7A—H7AA113.0
C4—C7—H7B113.0C4A—C7A—H7AB113.0
H7A—C7—H7B110.4H7AA—C7A—H7AB110.4
C1—N2—C3—C43.2 (3)C1A—N2A—C3A—C4A5.5 (3)
N2—C1—C6—N571.1 (2)N2A—C1A—C6A—N5A74.2 (2)
N2—C1—C7—C456.3 (2)N2A—C1A—C7A—C4A56.7 (2)
N2—C3—C4—N573.1 (2)N2A—C3A—C4A—N5A75.1 (2)
N2—C3—C4—C733.0 (3)N2A—C3A—C4A—C7A30.8 (3)
C3—C4—N5—C671.2 (2)C3A—C4A—N5A—C6A67.9 (2)
C3—C4—C7—C155.1 (2)C3A—C4A—C7A—C1A53.4 (2)
C4—N5—C6—C10.8 (3)C4A—N5A—C6A—C1A4.5 (2)
N5—C4—C7—C154.9 (2)N5A—C4A—C7A—C1A56.8 (2)
C6—C1—N2—C369.0 (2)C6A—C1A—N2A—C3A67.2 (2)
C6—C1—C7—C455.1 (2)C6A—C1A—C7A—C4A54.1 (2)
C7—C1—N2—C338.2 (2)C7A—C1A—N2A—C3A39.8 (2)
C7—C1—C6—N534.7 (2)C7A—C1A—C6A—N5A31.7 (2)
C7—C4—N5—C635.9 (2)C7A—C4A—N5A—C6A39.3 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H2A···Br30.93 (3)2.49 (3)3.358 (2)156 (2)
N5—H5A···Br40.92 (3)2.44 (3)3.261 (2)148 (3)
N5—H5B···Br1i0.78 (3)2.50 (3)3.242 (2)161 (3)
N2A—H2AA···Br30.89 (3)2.53 (4)3.344 (2)152 (3)
N2A—H2AB···Br1ii0.86 (3)2.48 (3)3.273 (2)155 (2)
N5A—H5AA···Br20.91 (3)2.42 (3)3.292 (2)160 (3)
N5A—H5AB···Br10.77 (3)2.77 (3)3.399 (2)140 (3)
Symmetry codes: (i) x+1, y1/2, z+3/2; (ii) x+1, y+1/2, z+3/2.
 

Acknowledgements

The authors thank the X-ray Diffraction Center and Center for Magnetic Resonance of Saint-Petersburg State University for instrumental and computational resources.

Funding information

Funding for this research was provided by: Saint-Petersburg State University (grant No. 0.37.235.2015).

References

First citationAlvaro, G., Di Fabio, R., Gualandi, A., Fiorelli, C., Monari, M., Savoia, D. & Zoli, L. (2007). Tetrahedron, 63, 12446–12453.  Web of Science CSD CrossRef CAS
First citationAnderson, D. J., Bunnelle, W., Surber, B., Du, J., Surowy, C., Tribollet, E., Marguerat, A., Bertrand, D. & Gopalakrishnan, M. (2008). J. Pharmacol. Exp. Ther. 324, 179–187.  Web of Science CrossRef PubMed CAS
First citationArtali, R., Bombieri, G. & Meneghetti, F. (2005). Farmaco, 60, 313–320.  CrossRef PubMed CAS
First citationAvila-Ortiz, C. G., Lopez-Ortiz, M., Vega-Penaloza, A., Regla, I. & Juaristi, E. (2015). Asymm. Catal. 2, 37–44.  CAS
First citationBeinat, C., Banister, S. D., McErlean, C. S. P. & Kassiou, M. (2013). Tetrahedron Lett. 54, 5345–5347.  Web of Science CrossRef CAS
First citationBeinat, C., Reekie, T., Banister, S. D., O'Brien-Brown, J., Xie, T., Olson, T. T., Xiao, Y., Harvey, A., O'Connor, S., Coles, C., Grishin, A., Kolesik, P., Tsanaktsidis, J. & Kassiou, M. (2015). Eur. J. Med. Chem. 95, 277–301.  Web of Science CrossRef CAS PubMed
First citationBertrand, D., Lee, C.-H. L., Flood, D., Marger, F. & Donnelly-Roberts, D. (2015). Pharmacol. Rev. 67, 1025–1073.  Web of Science CrossRef CAS PubMed
First citationBritvin, S. N. & Lotnyk, A. (2015). J. Am. Chem. Soc. 137, 5526–5535.  Web of Science CSD CrossRef CAS PubMed
First citationBritvin, S. N. & Rumyantsev, A. M. (2017a). Acta Cryst. E73, 1385–1388.  Web of Science CSD CrossRef IUCr Journals
First citationBritvin, S. N. & Rumyantsev, A. M. (2017b). Acta Cryst. E73, 1712–1715.  Web of Science CrossRef IUCr Journals
First citationBritvin, S. N., Rumyantsev, A. M., Silyutina, A. A. & Padkina, M. V. (2017a). ChemistrySelect, 2, 8721–8725.  Web of Science CSD CrossRef CAS
First citationBritvin, S. N., Rumyantsev, A. M., Zobnina, A. E. & Padkina, M. V. (2016). Chem. Eur. J. 22, 14227–14235.  Web of Science CSD CrossRef CAS PubMed
First citationBritvin, S. N., Rumyantsev, A. M., Zobnina, A. E. & Padkina, M. V. (2017b). J. Mol. Struct. 1130, 395–399.  Web of Science CSD CrossRef CAS
First citationBruker (2015). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.
First citationBujak, M. (2015). Cryst. Growth Des. 15, 1295–1302.  Web of Science CSD CrossRef CAS
First citationBunnelle, W. H., Daanen, J. F., Ryther, K. B., Schrimpf, M. R., Dart, M. J., Gelain, A., Meyer, M. D., Frost, J. M., Anderson, D. J., Buckley, M., Curzon, P., Cao, Y.-J., Puttfarcken, P., Searle, X., Ji, J., Putman, C. B., Surowy, C., Toma, L. & Barlocco, D. (2007). J. Med. Chem. 50, 3627–3644.  Web of Science CrossRef PubMed CAS
First citationCastillo, I., Pérez, V., Monsalvo, I., Demare, P. & Regla, I. (2013). Inorg. Chem. Commun. 38, 1–4.  Web of Science CSD CrossRef CAS
First citationCernak, T., Gesmundo, N. J., Dykstra, K., Yu, Y., Wu, Z., Shi, Z.-C., Vachal, P., Sperbeck, D., He, S., Murphy, B. A., Sonatore, L., Williams, S., Madeira, M., Verras, A., Reiter, M., Lee, C. H., Cuff, J., Sherer, E. C., Kuethe, J., Goble, S., Perrotto, N., Pinto, S., Shen, D.-M., Nargund, R., Balkovec, J., DeVita, R. J. & Dreher, S. D. (2017). J. Med. Chem. 60, 3594–3605.  Web of Science CrossRef CAS PubMed
First citationChoi, C., Nuhant, P., Mousseau, J. J., Yang, X., Gerstenberger, B. S., Williams, J. M. & Wright, S. W. (2016). Org. Lett. 18, 5748–5751.  Web of Science CSD CrossRef CAS PubMed
First citationCui, B., Yu, J., Yu, F.-C., Li, Y.-M., Chang, K.-J. & Shen, Y. (2015). RSC Adv. 5, 10386–10392.  Web of Science CrossRef CAS
First citationDam, J. H., Bender, D., Peters, D. & Någren, K. (2016). Nucl. Med. Biol. 43, 42–51.  Web of Science CrossRef CAS PubMed
First citationDíaz-de-Villegas, M. D., Gálvez, J. A., Badorrey, R. & López-Ram-de-Víu, P. (2014). Adv. Synth. Catal. 356, 3261–3288.
First citationDolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341.  Web of Science CrossRef CAS IUCr Journals
First citationFiorelli, C., Marchioro, C., Martelli, G., Monari, M. & Savoia, D. (2005). Eur. J. Org. Chem. 2005, 3987–3993.  Web of Science CSD CrossRef
First citationGerstenberger, B. S., Trzupek, J. D., Tallant, C., Fedorov, O., Filippakopoulos, P., Brennan, P. E., Fedele, V., Martin, S., Picaud, S., Rogers, C., Parikh, M., Taylor, A., Samas, B., O'Mahony, A., Berg, E., Pallares, G., Torrey, A. D., Treiber, D. K., Samardjiev, I. J., Nasipak, B. T., Padilla-Benavides, T., Wu, Q., Imbalzano, A. N., Nickerson, J. A., Bunnage, M. E., Müller, S., Knapp, S. & Owen, D. R. (2016). J. Med. Chem. 59, 4800–4811.  Web of Science CSD CrossRef CAS PubMed
First citationGonzález-Olvera, R., Demare, P., Regla, I. & Juaristi, E. (2008). Arkivoc, 6, 61–72.
First citationGroom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179.  Web of Science CSD CrossRef IUCr Journals
First citationHamblett, C. L., Methot, J. L., Mampreian, D. M., Sloman, D. L., Stanton, M. G., Kral, A. M., Fleming, J. C., Cruz, J. C., Chenard, M., Ozerova, N., Hitz, A. M., Wang, H., Deshmukh, S. V., Nazef, N., Harsch, A., Hughes, B., Dahlberg, W. K., Szewczak, A. A., Middleton, R. E., Mosley, R. T., Secrist, J. P. & Miller, T. A. (2007). Bioorg. Med. Chem. Lett. 17, 5300–5309.  Web of Science CrossRef PubMed CAS
First citationJordis, U., Kesselgruber, M., Nerdinger, S. & Mereiter, K. (1999). Mendeleev Commun. 9, 147–148.  CSD CrossRef
First citationJordis, U., Sauter, F., Siddiqi, S. M., Küenburg, B. & Bhattacharya, K. (1990). Synthesis, pp. 925–930.  CrossRef
First citationKiely, J. S., Hutt, M. P., Culbertson, T. P., Bucsh, R. A., Worth, D. F., Lesheski, L. E., Gogliotti, R. D., Sesnie, J. C., Solomon, M. & Mich, T. F. (1991). J. Med. Chem. 34, 656–663.  CrossRef PubMed CAS Web of Science
First citationKrasnov, V., Nizova, I. A., Vigorov, A. Yu., Matveeva, T. V., Levit, G. L., Slepukhin, P. A., Ezhikova, M. A. & Kodess, M. I. (2008). Eur. J. Org. Chem. pp. 1802–1810.  Web of Science CSD CrossRef
First citationLaskar, S., Sánchez-Sánchez, L., López-Ortiz, M., López-Muñoz, H., Escobar-Sánchez, M. L., Sánchez, A. T. & Regla, I. (2017). J. Enzyme Inhib. Med. Chem. 32, 1129–1135.  Web of Science CrossRef CAS PubMed
First citationLauteslager, X. Y., van Stokkum, I. M., van Ramesdonk, H. J., Bebelaar, D., Fraanje, J., Goubitz, K., Schenk, H., Brouwer, A. M. & Verhoeven, J. W. (2001). Eur. J. Org. Chem. pp. 3105–3118.  CrossRef
First citationLi, T., Bunnelle, W. H., Ryther, K. B., Anderson, D. J., Malysz, J., Helfrich, R., Grønlien, J. H., Håkerud, M., Peters, D., Schrimpf, M. R., Gopalakrishnan, M. & Ji, J. (2010). Bioorg. Med. Chem. Lett. 20, 3636–3639.  Web of Science CrossRef CAS PubMed
First citationLlona-Minguez, S., Höglund, A., Ghassemian, A., Desroses, M., Calderón-Montaño, J. M., Burgos Morón, E., Valerie, N. C. K., Wiita, E., Almlöf, I., Koolmeister, T., Mateus, A., Cazares-Körner, C., Sanjiv, K., Homan, E., Loseva, O., Baranczewski, P., Darabi, M., Mehdizadeh, A., Fayezi, S., Jemth, A.-S., Warpman Berglund, U., Sigmundsson, K., Lundbäck, T., Jenmalm Jensen, A., Artursson, P., Scobie, M. & Helleday, T. (2017). J. Med. Chem. 60, 4279–4292.  Web of Science CAS PubMed
First citationLópez-Ortiz, M., Monsalvo, I., Demare, P., Paredes, C., Mascher, D., Hernández, C., Hernández, M. & Regla, I. (2014). Chem. Biol. Drug Des. 83, 710–720.  Web of Science PubMed
First citationMacrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466–470.  Web of Science CSD CrossRef CAS IUCr Journals
First citationMcGuirk, P. R., Jefson, M. R., Mann, D. D., Elliott, N. C., Chang, P., Cisek, E. P., Cornell, C. P., Gootz, T. D., Haskell, S. L., Hindahl, M. S., LaFleur, L. J., Rosenfeld, M. J., Shryock, T. R., Silvia, A. M. & Weber, F. H. (1992). J. Med. Chem. 35, 611–620.  CrossRef PubMed CAS Web of Science
First citationMelgar-Fernández, R., González-Olvera, R., Olivares-Romero, J. L., González-López, V., Romero-Ponce, L., del Refugio Ramírez-Zárate, M., Demare, P., Regla, I. & Juaristi, E. (2008). Eur. J. Org. Chem. pp. 655–672.
First citationMereiter, K., Skubak, J. & Jordis, U. (2007). Private communication (deposition number 664942). CCDC, Cambridge, England.
First citationMurineddu, G., Asproni, B., Pinna, G., Curzu, M. M., Dore, A., Pau, A., Deligia, F. & Pinna, G. A. (2012). Curr. Med. Chem. 19, 5342–5363.  CrossRef CAS PubMed
First citationParsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259.  Web of Science CrossRef CAS IUCr Journals
First citationPatel, R. V. & Park, S. W. (2013). Mini Rev. Med. Chem. 13, 1579–1601.  CrossRef CAS PubMed
First citationPérez, V., Monsalvo, I., Demare, P., Gómez-Vidales, V., Regla, I. & Castillo, I. (2011). Inorg. Chem. Commun. 14, 389–391.
First citationPortoghese, P. S. & Mikhail, A. A. (1966). J. Org. Chem. 31, 1059–1062.  CrossRef CAS Web of Science
First citationRemuzon, P., Bouzard, D., Clemencin, C., Dussy, C., Jacquet, J. P., Fung-Tome, J. & Kessler, R. E. (1993). Eur. J. Med. Chem. 28, 455–461.  CrossRef CAS Web of Science
First citationSenGupta, S., Maiti, N., Chadha, R. & Kapoor, S. (2014). Chem. Phys. 436–437, 55–62.  Web of Science CrossRef CAS
First citationShchekotikhin, A. E., Glazunova, V. A., Dezhenkova, L. G., Luzikov, Y. N., Buyanov, V. N., Treshalina, H. M., Lesnaya, N. A., Romanenko, V. I., Kaluzhny, D. N., Balzarini, J., Agama, K., Pommier, Y., Shtil, A. A. & Preobrazhenskaya, M. N. (2014). Eur. J. Med. Chem. 86, 797–805.  Web of Science CrossRef CAS PubMed
First citationSheldrick, G. M. (2015a). Acta Cryst. A71, 3–8.  Web of Science CrossRef IUCr Journals
First citationSheldrick, G. M. (2015b). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals
First citationSiebeneicher, H., Bauser, M., Buchmann, B., Heisler, I., Müller, T., Neuhaus, R., Rehwinkel, H., Telser, J. & Zorn, L. (2016). Bioorg. Med. Chem. Lett. 26, 1732–1737.  Web of Science CrossRef CAS PubMed
First citationToma, L., Quadrelli, P., Bunnelle, W. H., Anderson, D. J., Meyer, M. D., Cignarella, G., Gelain, A. & Barlocco, D. (2002). J. Med. Chem. 45, 4011–4017.  Web of Science CrossRef PubMed CAS
First citationWei, M., Zhang, X., Wang, X., Song, Z., Ding, J., Meng, L.-H. & Zhang, A. (2017). Eur. J. Med. Chem. 125, 1156–1171.  Web of Science CrossRef CAS PubMed
First citationWestrip, S. P. (2010). J. Appl. Cryst. 43, 920–925.  Web of Science CrossRef CAS IUCr Journals
First citationWu, C., Zhang, J., Li, P., Zhang, J. & Wu, J. (2011). Acta Cryst. E67, o272.  Web of Science CSD CrossRef IUCr Journals
First citationYakovlev, M. E., Lobanov, P. S. & Potekhin, A. A. (2000). Chem. Heterocycl. Compd, 36, 429–431.  CrossRef CAS

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Follow Acta Cryst. E
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds