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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoIUCrDATA
ISSN: 2414-3146
Volume 8| Part 1| January 2023| x230025
https://doi.org/10.1107/S2414314623000251

Methyl 1-[(6-meth­­oxy-5-methyl­pyrimidin-4-yl)meth­yl]-1H-benzo[d]imidazole-7-carboxyl­ate: a combined X-ray and DFT study

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Adrian Richter,a Richard Goddard,b Roy Schönefeld,a Peter Imminga and Rüdiger W. Seidela*

aInstitut für Pharmazie, Martin-Luther-Universität Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle (Saale), Germany, and bMax-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany
*Correspondence e-mail: ruediger.seidel@pharmazie.uni-halle.de

Edited by M. Bolte, Goethe-Universität Frankfurt, Germany (Received 5 January 2023; accepted 10 January 2023; online 12 January 2023)

The title compound, C16H16N4O3, was obtained as a side product during the synthesis of the previously reported anti­tubercular agent N-(2-fluoro­eth­yl)-1-[(6-meth­oxy-5-methyl­pyrimidin-4-yl)meth­yl]-1H-benzo[d]imidazole-4-carboxamide and structurally characterized by X-ray crystallography and computational methods. In the crystal (space group P21/n, Z = 4), the title compound adopts a twisted conformation with a dihedral angle between the benzimidazole and pyrimidine mean planes of 84.11 (3)°. The carboxyl­ate group and the 5-methyl group on the pyrimidine ring exhibit partial disorder. The DFT-optimized mol­ecular structure resembles the structure of the minor component in the crystal.

CCDC reference: 2235406

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[Scheme 3D1]
Chemical scheme
[Scheme 1]

Structure description

In the course of our studies on anti­mycobacterial agents, we synthesized and studied the compound N-(2-fluoro­eth­yl)-1-[(6-meth­oxy-5-methyl­pyrimidin-4-yl)meth­yl]-1H-benzo[d]imidazole-4-carboxamide (Richter et al., 2022[Richter, A., Goddard, R., Schönefeld, R., Imming, P. & Seidel, R. W. (2022). Acta Cryst. E78, 1184-1188.]), a benzimidazole analogue of the 1,4-aza­indole-based anti­tuberculosis clinical drug candidate TBA-7371 (Shirude et al., 2013[Shirude, P. S., Shandil, R., Sadler, C., Naik, M., Hosagrahara, V., Hameed, S., Shinde, V., Bathula, C., Humnabadkar, V., Kumar, N., Reddy, J., Panduga, V., Sharma, S., Ambady, A., Hegde, N., Whiteaker, J., McLaughlin, R. E., Gardner, H., Madhavapeddi, P., Ramachandran, V., Kaur, P., Narayan, A., Guptha, S., Awasthy, D., Narayan, C., Mahadevaswamy, J., Vishwas, K. G., Ahuja, V., Srivastava, A., Prabhakar, K. R., Bharath, S., Kale, R., Ramaiah, M., Choudhury, N. R., Sambandamurthy, V. K., Solapure, S., Iyer, P. S., Narayanan, S. & Chatterji, M. (2013). J. Med. Chem. 56, 9701-9708.], 2014[Shirude, P. S., Shandil, R. K., Manjunatha, M. R., Sadler, C., Panda, M., Panduga, V., Reddy, J., Saralaya, R., Nanduri, R., Ambady, A., Ravishankar, S., Sambandamurthy, V. K., Humnabadkar, V., Jena, L. K., Suresh, R. S., Srivastava, A., Prabhakar, K. R., Whiteaker, J., McLaughlin, R. E., Sharma, S., Cooper, C. B., Mdluli, K., Butler, S., Iyer, P. S., Narayanan, S. & Chatterji, M. (2014). J. Med. Chem. 57, 5728-5737.]), following the route published by Manjunatha et al. (2019[Manjunatha, M. R., Radha Shandil, R., Panda, M., Sadler, C., Ambady, A., Panduga, V., Kumar, N., Mahadevaswamy, J., Sreenivasaiah, M., Narayan, A., Guptha, S., Sharma, S., Sambandamurthy, V. K., Ramachandran, V., Mallya, M., Cooper, C., Mdluli, K., Butler, S., Tommasi, R., Iyer, P. S., Narayanan, S., Chatterji, M. & Shirude, P. S. (2019). ACS Med. Chem. Lett. 10, 1480-1485.]). Therein, methyl 1H-benzo[d]imidazole-4-carboxyl­ate (1) is N-alkyl­ated with 4-(chloro­meth­yl)-6-meth­oxy-5-methyl­pyrimidine to yield the desired methyl 1-[(6-meth­oxy-5-methyl­pyrimidin-4-yl)meth­yl]-1H-benzo[d]imidazole-4-carboxyl­ate (2) and its structural isomer methyl 1-[(6-meth­oxy-5-methyl­pyrimidin-4-yl)meth­yl]-1H-benzo[d]imidazole-7-carboxyl­ate (3), the title compound, as a side product (Fig. 1[link]). After separation by flash chromatography, the ratio of 2 and 3 was approximately 3.75:1 (Richter et al., 2022[Richter, A., Goddard, R., Schönefeld, R., Imming, P. & Seidel, R. W. (2022). Acta Cryst. E78, 1184-1188.]). We have now structurally characterized compound 3 by X-ray crystallography and computational methods.

[Figure 1]
Figure 1
N-Alkyl­ation of 1 with 4-(chloro­meth­yl)-6-meth­oxy-5-methyl­pyrimidine to yield structural isomers 2 and 3.

Fig. 2[link] shows the mol­ecular structure of 3 in the crystal. The mol­ecule exhibits an angular shape, similar to the aforementioned N-(2-fluoro­eth­yl)-1-[(6-meth­oxy-5-methyl­pyrimidin-4-yl)meth­yl]-1H-benzo[d]imidazole-4-carboxamide in the crystal (CSD refcode: DEVGEU; Richter et al., 2022[Richter, A., Goddard, R., Schönefeld, R., Imming, P. & Seidel, R. W. (2022). Acta Cryst. E78, 1184-1188.]). In 3, the angle between the mean planes through the benzimidazole moiety and the pyrimidine ring is 84.11 (3)°. The C2—N1—C10—C11 torsion angle is −87.61 (6)° in the chosen asymmetric unit, but the oppositely handed conformer is present in the centrosymmetric crystal structure. The methyl group on the pyrimidine ring and the carbonyl oxygen atom of the carboxyl­ate group each were found to be partially disordered over two positions. The two orientations taken up by the methyl group of C16 may cause the carboxyl­ate group to move slightly, hence the minor component O2′. To gain insight into the structural features of 3, we optimized the structure of an isolated mol­ecule by DFT calculations. An overlay of the mol­ecular structures from X-ray crystallography and DFT structure optimization (Fig. 3[link]) reveals that the conformation of the minor-disorder component in the crystal structure is very similar to the DFT-optimized structure. The latter exhibits a relatively short intra­molecular C—H⋯O contact between oxygen atom of the carbonyl group and one of the hydrogen atoms of the bridging methyl­ene group (O⋯H = 2.13 Å).

[Figure 2]
Figure 2
Displacement ellipsoid plot of 3 (50% probability level). Hydrogen atoms are represented by small spheres of arbitrary radius. Disordered parts with minor occupancy are drawn with empty bonds.
[Figure 3]
Figure 3
Structure overlay plot of the mol­ecular structure of 3 in the crystal (green; displacement ellipsoids with 50% probability) and the DFT-optimized mol­ecular structure (orange). The respective benzimidazole moieties were superimposed (r.m.s deviation for non-hydrogen atoms: 0.024 Å).

The solid-state structure of 3 appears to be governed by close packing. The packing index calculated with PLATON (Spek, 2020[Spek, A. L. (2020). Acta Cryst. E76, 1-11.]) for the major disorder part is 73.8%, indicating a dense crystal packing (Kitaigorodskii, 1973[Kitaigorodskii, A. I. (1973). Molecular crystals and molecules. London: Academic Press.]). As shown in Fig. 4[link], face-to-face π–π stacking each between the benzimid­azole and pyrimidine systems of adjacent mol­ecules is a dominating structural motif. It is inter­esting to note that, in contrast to DEVGEU, the benzimidazole C2—H2 group does not form short C—H⋯X (X = N, O) contacts in the crystal structure of 3.

[Figure 4]
Figure 4
Section of the crystal structure of 3. Colour scheme: carbon, grey; nitro­gen, blue; oxygen, red. Hydrogen atoms and O2′ are omitted for clarity.

Synthesis and crystallization

We obtained compound 3 as a side product in the deliberate synthesis of its structural isomer 2, following the route published by Manjunatha et al. (2019[Manjunatha, M. R., Radha Shandil, R., Panda, M., Sadler, C., Ambady, A., Panduga, V., Kumar, N., Mahadevaswamy, J., Sreenivasaiah, M., Narayan, A., Guptha, S., Sharma, S., Sambandamurthy, V. K., Ramachandran, V., Mallya, M., Cooper, C., Mdluli, K., Butler, S., Tommasi, R., Iyer, P. S., Narayanan, S., Chatterji, M. & Shirude, P. S. (2019). ACS Med. Chem. Lett. 10, 1480-1485.]). The isomers were separated by flash chromatography (Richter et al., 2022[Richter, A., Goddard, R., Schönefeld, R., Imming, P. & Seidel, R. W. (2022). Acta Cryst. E78, 1184-1188.]). Crystals of 3 suitable for X-ray crystallography were obtained as follows: Slow evaporation of a solution of the compound in chloro­form-d to dryness yielded a powder, which was redissolved in methanol. The solution thus obtained was again set aside at room temperature, and the solvent was allowed to evaporate slowly. Colourless crystals appeared after the vessel had been left undisturbed for a couple of weeks.

Refinement

Crystal data, data collection and structure refinement details are listed in Table 1[link]. Initial independent-atom model refinement was carried out with SHELXL2018 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]). The final structure refinement was carried out by Hirshfeld atom refinement with non-spherical atomic form factors factors using NoSpherA2 (Kleemiss et al., 2021[Kleemiss, F., Dolomanov, O. V., Bodensteiner, M., Peyerimhoff, N., Midgley, M., Bourhis, L. J., Genoni, A., Malaspina, L. A., Jayatilaka, D., Spencer, J. L., White, F., Grundkötter-Stock, B., Steinhauer, S., Lentz, D., Puschmann, H. & Grabowsky, S. (2021). Chem. Sci. 12, 1675-1692.]; Midgley et al., 2021[Midgley, L., Bourhis, L. J., Dolomanov, O. V., Grabowsky, S., Kleemiss, F., Puschmann, H. & Peyerimhoff, N. (2021). Acta Cryst. A77, 519-533.]) partitioning in 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.]) based on electron density from iterative single-determinant SCF single-point DFT calculations using ORCA (version 4.1.1; Neese et al., 2020[Neese, F., Wennmohs, F., Becker, U. & Riplinger, C. (2020). J. Chem. Phys. 152, 224108.]) with a B3LYP functional (Becke, 1993[Becke, A. D. (1993). J. Chem. Phys. 98, 5648-5652.]; Lee et al., 1988[Lee, C., Yang, W. & Parr, R. G. (1988). Phys. Rev. B, 37, 785-789.]) and a def2-TZVPP basis set (Weigend & Ahlrichs, 2005[Weigend, F. & Ahlrichs, R. (2005). Phys. Chem. Chem. Phys. 7, 3297-3305.]). The carbonyl oxygen atom (O2) and the methyl hydrogen atoms on C16 were found to be disordered over two positions in each case. Standard similar distance restraints were applied to the C8—O2 and C8—O2′ distances as well as on the 1,2- and 1,3-distances of the disordered methyl hydrogen atoms. The ratio of occupancy was refined by means of a free variable for each disordered group to give 0.63 (4):0.37 (4) for the carbonyl oxygen atom and 0.646 (12):0.354 (12) for the hydrogen atoms of the methyl group. Uiso values of hydrogen atoms were refined freely, except for those affected by disorder, for which Uiso(H) = 1.5Ueq(C) was set.

Table 1
Experimental details

Crystal data
Chemical formula C16H16N4O3
Mr 312.33
Crystal system, space group Monoclinic, P21/n
Temperature (K) 100
a, b, c (Å) 9.3758 (7), 4.7862 (3), 32.764 (2)
β (°) 96.340 (3)
V (Å3) 1461.28 (18)
Z 4
Radiation type Mo Kα
μ (mm−1) 0.10
Crystal size (mm) 0.19 × 0.10 × 0.02
 
Data collection
Diffractometer Bruker AXS D8 VENTURE
Absorption correction Gaussian (SADABS; Krause et al., 2015[Krause, L., Herbst-Irmer, R., Sheldrick, G. M. & Stalke, D. (2015). J. Appl. Cryst. 48, 3-10.])
Tmin, Tmax 0.986, 0.998
No. of measured, independent and observed [I ≥ 2u(I)] reflections 125687, 6375, 5698
Rint 0.047
(sin θ/λ)max (Å−1) 0.814
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.039, 0.061, 1.07
No. of reflections 6375
No. of parameters 289
No. of restraints 20
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.41, −0.40
Computer programs: APEX4 (Bruker, 2017[Bruker (2017). APEX4. Bruker AXS Inc., Madison, Wisconsin, USA.]), SAINT (Bruker, 2004[Bruker (2004). SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXT (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), OLEX2.refine (Bourhis et al., 2015[Bourhis, L. J., Dolomanov, O. V., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2015). Acta Cryst. A71, 59-75.]), DIAMOND (Brandenburg, 2018[Brandenburg, K. (2018). DIAMOND. Crystal Impact GbR, Bonn, Germany.]) and Mercury (Macrae et al., 2020[Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226-235.]), publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

DFT structure optimization of an isolated mol­ecule of 3 was undertaken using ORCA (version 5.0; Neese et al., 2020[Neese, F., Wennmohs, F., Becker, U. & Riplinger, C. (2020). J. Chem. Phys. 152, 224108.]) with a B3LYP(G) (VWN1) hybrid functional (20% HF exchange) (Becke, 1993[Becke, A. D. (1993). J. Chem. Phys. 98, 5648-5652.]; Lee et al., 1988[Lee, C., Yang, W. & Parr, R. G. (1988). Phys. Rev. B, 37, 785-789.]; Hertwig & Koch, 1997[Hertwig, R. H. & Koch, W. (1997). Chem. Phys. Lett. 268, 345-351.]), using a def2-TZVPP basis set (Weigend & Ahlrichs, 2005[Weigend, F. & Ahlrichs, R. (2005). Phys. Chem. Chem. Phys. 7, 3297-3305.]) utilizing the auxiliary basis def2/J (Weigend, 2006[Weigend, F. (2006). Phys. Chem. Chem. Phys. 8, 1057-1065.]). The input structure was generated from the major disorder component in the crystal structure. Optimization of the structures used the BFGS method from an initial Hessian according to Almoef's model with a very tight self-consistent field convergence threshold (Fletcher, 2000[Fletcher, R. (2000). Practical Methods of Optimization, 2nd ed. Chichester: John Wiley & Sons.]). The optimized local minimum-energy structure exhibited only positive frequencies.

Structural data

CCDC reference: 2235406

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S2414314623000251/bt4130sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314623000251/bt4130Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314623000251/bt4130Isup3.cdx

ATR-FT-IR spectrum of compound 3. DOI: https://doi.org/10.1107/S2414314623000251/bt4130sup4.pdf

Cartesian coordinates of the DFT-calculated molecular structure of compound 3. DOI: https://doi.org/10.1107/S2414314623000251/bt4130sup4.txt

Supporting information file. DOI: https://doi.org/10.1107/S2414314623000251/bt4130Isup6.cml

checkCIF report


Computing details top

Data collection: APEX4 (Bruker, 2017); cell refinement: SAINT (Bruker, 2004); data reduction: SAINT (Bruker, 2004); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: olex2.refine (Bourhis et al., 2015); molecular graphics: DIAMOND (Brandenburg, 2018) and Mercury (Macrae et al., 2020); software used to prepare material for publication: publCIF (Westrip, 2010).

Methyl 1-[(6-methoxy-5-methylpyrimidin-4-yl)methyl]-1H-benzo[d]imidazole-7-carboxylate top
Crystal data top
C16H16N4O3F(000) = 656.464
Mr = 312.33Dx = 1.420 Mg m−3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
a = 9.3758 (7) ÅCell parameters from 9856 reflections
b = 4.7862 (3) Åθ = 2.2–34.0°
c = 32.764 (2) ŵ = 0.10 mm−1
β = 96.340 (3)°T = 100 K
V = 1461.28 (18) Å3Needle
Z = 40.19 × 0.10 × 0.02 mm
Data collection top
Bruker AXS D8 VENTURE
diffractometer		6375 independent reflections
Radiation source: IµS DIAMOND5698 reflections with I ≥ 2u(I)
Incoatec multilayer optics monochromatorRint = 0.047
Detector resolution: 7.391 pixels mm-1θmax = 35.4°, θmin = 2.2°
φ– and ω–scansh = −15→15
Absorption correction: gaussian
(SADABS; Krause et al., 2015)		k = −7→7
Tmin = 0.986, Tmax = 0.998l = −53→52
125687 measured reflections
Refinement top
Refinement on F2Primary atom site location: dual
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.039Hydrogen site location: difference Fourier map
wR(F2) = 0.061H atoms treated by a mixture of independent and constrained refinement
S = 1.07 w = 1/[σ2(Fo2) + (0.0015P)2 + 0.4692P]
where P = (Fo2 + 2Fc2)/3
6375 reflections(Δ/σ)max = 0.001
289 parametersΔρmax = 0.41 e Å−3
20 restraintsΔρmin = −0.40 e Å−3
8 constraints
Special details top

Experimental. Crystal mounted on a MiTeGen loop using Perfluoropolyether PFO-XR75

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
C20.41793 (7)0.30578 (14)0.347562 (19)0.01418 (11)
H20.3810 (9)0.143 (2)0.3663 (3)0.030 (2)*
C3A0.43336 (6)0.62087 (13)0.302844 (18)0.01290 (10)
C40.40396 (7)0.80361 (15)0.269895 (19)0.01730 (12)
H40.2991 (10)0.811 (2)0.2534 (3)0.036 (3)*
C50.51499 (8)0.96871 (15)0.25906 (2)0.01903 (12)
H50.4962 (10)1.114 (2)0.2346 (3)0.041 (3)*
C60.65157 (7)0.95258 (14)0.280843 (19)0.01600 (11)
H60.7336 (10)1.083 (2)0.2723 (3)0.038 (3)*
C70.68523 (6)0.77003 (13)0.313947 (17)0.01144 (10)
C7A0.57230 (6)0.59893 (12)0.324773 (17)0.00994 (9)
C80.83210 (7)0.77743 (14)0.336015 (19)0.01473 (11)
C91.06327 (8)0.9716 (2)0.33753 (3)0.02662 (16)
H9a1.1186 (11)0.774 (2)0.3367 (3)0.046 (3)*
H9b1.1135 (12)1.129 (3)0.3209 (3)0.057 (3)*
H9c1.0648 (12)1.029 (3)0.3683 (4)0.054 (3)*
C100.65713 (7)0.27497 (13)0.385944 (18)0.01206 (10)
H10a0.7645 (9)0.270 (2)0.3765 (3)0.024 (2)*
H10b0.6245 (10)0.064 (2)0.3908 (3)0.031 (2)*
C110.65753 (6)0.43198 (12)0.426058 (17)0.01067 (10)
C120.75223 (6)0.35346 (13)0.459654 (18)0.01303 (10)
C130.73550 (7)0.49763 (15)0.496289 (18)0.01579 (12)
C140.55770 (7)0.76028 (14)0.464026 (19)0.01531 (11)
H140.4812 (10)0.925 (2)0.4657 (3)0.034 (2)*
C150.80160 (9)0.5572 (3)0.56782 (2)0.0335 (2)
H15a0.8874 (11)0.483 (2)0.5890 (3)0.048 (3)*
H15b0.8061 (12)0.782 (3)0.5644 (3)0.053 (3)*
H15c0.7008 (12)0.496 (3)0.5774 (3)0.053 (3)*
C160.86532 (7)0.13435 (16)0.45806 (2)0.02042 (13)
H16a0.8658 (17)−0.003 (3)0.4854 (4)0.03063 (19)*0.646 (12)
H16b0.8514 (16)0.001 (3)0.4320 (4)0.03063 (19)*0.646 (12)
H16c0.9698 (13)0.230 (3)0.4614 (5)0.03063 (19)*0.646 (12)
H16d0.932 (3)0.191 (5)0.4335 (7)0.03063 (19)*0.354 (12)
H16e0.815 (2)−0.059 (4)0.4467 (8)0.03063 (19)*0.354 (12)
H16f0.934 (3)0.101 (6)0.4846 (6)0.03063 (19)*0.354 (12)
N10.55809 (5)0.38936 (11)0.353175 (15)0.01077 (9)
N30.33883 (6)0.43622 (13)0.318270 (17)0.01624 (10)
N40.56045 (6)0.63817 (11)0.427757 (15)0.01239 (9)
N50.63968 (6)0.69880 (13)0.498873 (16)0.01738 (11)
O10.91869 (5)0.94660 (12)0.318121 (17)0.02457 (11)
O20.8667 (4)0.6788 (12)0.36899 (8)0.0202 (7)0.63 (4)
O2'0.8822 (11)0.606 (5)0.3628 (6)0.040 (3)0.37 (4)
O30.82283 (5)0.42339 (13)0.529660 (14)0.02307 (11)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C20.0136 (2)0.0155 (3)0.0133 (2)−0.0044 (2)0.00101 (19)0.0002 (2)
C3A0.0127 (2)0.0141 (2)0.0112 (2)0.0007 (2)−0.00191 (18)−0.0002 (2)
C40.0193 (3)0.0185 (3)0.0128 (3)0.0042 (2)−0.0039 (2)0.0019 (2)
C50.0263 (3)0.0176 (3)0.0127 (3)0.0036 (3)0.0002 (2)0.0053 (2)
C60.0215 (3)0.0139 (3)0.0131 (2)−0.0006 (2)0.0042 (2)0.0028 (2)
C70.0132 (2)0.0112 (2)0.0101 (2)−0.0013 (2)0.00209 (18)−0.00018 (19)
C7A0.0108 (2)0.0104 (2)0.0083 (2)−0.00019 (19)−0.00006 (17)−0.00010 (18)
C80.0137 (2)0.0185 (3)0.0121 (2)−0.0046 (2)0.00212 (19)−0.0016 (2)
C90.0180 (3)0.0330 (4)0.0292 (4)−0.0117 (3)0.0044 (3)−0.0039 (3)
C100.0158 (2)0.0102 (2)0.0099 (2)0.0013 (2)−0.00020 (19)0.00046 (19)
C110.0137 (2)0.0097 (2)0.0083 (2)−0.00153 (19)−0.00023 (18)0.00081 (18)
C120.0137 (2)0.0140 (3)0.0106 (2)−0.0028 (2)−0.00208 (19)0.0020 (2)
C130.0158 (3)0.0217 (3)0.0094 (2)−0.0077 (2)−0.00081 (19)0.0008 (2)
C140.0178 (3)0.0158 (3)0.0128 (2)−0.0021 (2)0.0038 (2)−0.0032 (2)
C150.0198 (3)0.0690 (7)0.0109 (3)−0.0133 (4)−0.0013 (2)−0.0033 (4)
C160.0153 (3)0.0203 (3)0.0242 (3)0.0007 (2)−0.0044 (2)0.0051 (3)
N10.0120 (2)0.0113 (2)0.00872 (19)−0.00109 (17)0.00008 (15)0.00024 (17)
N30.0110 (2)0.0203 (3)0.0166 (2)−0.0027 (2)−0.00210 (18)−0.0011 (2)
N40.0158 (2)0.0115 (2)0.0099 (2)0.00026 (18)0.00143 (17)−0.00015 (17)
N50.0189 (2)0.0234 (3)0.0101 (2)−0.0071 (2)0.00264 (18)−0.0043 (2)
O10.0175 (2)0.0267 (3)0.0297 (3)−0.0083 (2)0.00328 (19)0.0061 (2)
O20.0140 (6)0.0305 (12)0.0153 (9)−0.0053 (6)−0.0022 (4)0.0069 (6)
O2'0.0159 (15)0.054 (5)0.047 (3)−0.014 (2)−0.0119 (19)0.030 (4)
O30.0194 (2)0.0376 (3)0.01085 (19)−0.0088 (2)−0.00411 (16)0.0020 (2)
Geometric parameters (Å, º) top
C2—H21.071 (9)C10—H10b1.074 (10)
C2—N11.3666 (8)C10—C111.5136 (8)
C2—N31.3052 (8)C10—N11.4472 (7)
C3A—C41.3931 (9)C11—C121.3876 (8)
C3A—C7A1.4204 (8)C11—N41.3478 (8)
C3A—N31.3860 (8)C12—C131.4082 (9)
C4—H41.069 (9)C12—C161.4963 (10)
C4—C51.3841 (10)C13—N51.3259 (9)
C5—H51.062 (10)C13—O31.3395 (8)
C5—C61.3975 (10)C14—H141.073 (10)
C6—H61.051 (10)C14—N41.3271 (8)
C6—C71.4013 (8)C14—N51.3368 (8)
C7—C7A1.4143 (8)C15—H15a1.064 (11)
C7—C81.4834 (9)C15—H15b1.084 (13)
C7A—N11.3846 (7)C15—H15c1.070 (11)
C8—O11.3280 (8)C15—O31.4381 (10)
C8—O21.191 (4)C16—H16a1.111 (11)
C8—O2'1.255 (8)C16—H16b1.060 (11)
C9—H9a1.080 (12)C16—H16c1.076 (11)
C9—H9b1.069 (12)C16—H16d1.105 (15)
C9—H9c1.043 (11)C16—H16e1.085 (15)
C9—O11.4374 (9)C16—H16f1.035 (15)
C10—H10a1.085 (9)
N1—C2—H2120.2 (5)C16—C12—C11123.78 (6)
N3—C2—H2125.1 (5)C16—C12—C13121.28 (6)
N3—C2—N1114.76 (6)N5—C13—C12123.39 (6)
C7A—C3A—C4122.03 (6)O3—C13—C12116.75 (6)
N3—C3A—C4127.10 (6)O3—C13—N5119.86 (6)
N3—C3A—C7A110.86 (5)N4—C14—H14116.8 (5)
H4—C4—C3A120.3 (5)N5—C14—H14116.2 (5)
C5—C4—C3A117.85 (6)N5—C14—N4126.99 (6)
C5—C4—H4121.9 (5)H15b—C15—H15a111.3 (9)
H5—C5—C4120.1 (5)H15c—C15—H15a110.2 (8)
C6—C5—C4120.68 (6)H15c—C15—H15b110.5 (9)
C6—C5—H5119.2 (5)O3—C15—H15a104.5 (6)
H6—C6—C5119.1 (5)O3—C15—H15b109.9 (6)
C7—C6—C5123.02 (6)O3—C15—H15c110.2 (6)
C7—C6—H6117.9 (5)H16a—C16—C12109.1 (8)
C7A—C7—C6116.38 (5)H16b—C16—C12115.1 (8)
C8—C7—C6118.68 (6)H16b—C16—H16a106.4 (10)
C8—C7—C7A124.88 (5)H16c—C16—C12109.8 (8)
C7—C7A—C3A120.03 (5)H16c—C16—H16a104.3 (10)
N1—C7A—C3A104.04 (5)H16c—C16—H16b111.6 (10)
N1—C7A—C7135.91 (5)H16d—C16—C12108.1 (13)
O1—C8—C7112.29 (6)H16d—C16—H16a141.4 (15)
O2—C8—C7125.30 (16)H16d—C16—H16b65.9 (14)
O2—C8—O1121.60 (15)H16d—C16—H16c52.4 (13)
O2'—C8—C7125.5 (3)H16e—C16—C12109.2 (13)
O2'—C8—O1120.6 (3)H16e—C16—H16a74.6 (14)
H9b—C9—H9a111.2 (8)H16e—C16—H16c138.8 (16)
H9c—C9—H9a107.4 (9)H16e—C16—H16d102.6 (15)
H9c—C9—H9b110.5 (9)H16f—C16—C12117.2 (13)
O1—C9—H9a110.4 (6)H16f—C16—H16b126.2 (16)
O1—C9—H9b106.2 (6)H16f—C16—H16c60.3 (14)
O1—C9—H9c111.2 (6)H16f—C16—H16d107.5 (15)
H10b—C10—H10a108.2 (7)H16f—C16—H16e111.2 (17)
C11—C10—H10a110.1 (5)C7A—N1—C2106.50 (5)
C11—C10—H10b108.1 (5)C10—N1—C2121.18 (5)
N1—C10—H10a109.6 (5)C10—N1—C7A132.16 (5)
N1—C10—H10b107.3 (5)C3A—N3—C2103.82 (5)
N1—C10—C11113.34 (5)C14—N4—C11116.07 (5)
C12—C11—C10119.63 (5)C14—N5—C13115.79 (5)
N4—C11—C10117.55 (5)C9—O1—C8116.61 (6)
N4—C11—C12122.78 (5)C15—O3—C13117.44 (7)
C13—C12—C11114.94 (6)
C2—N1—C7A—C3A−1.20 (5)C6—C7—C8—O2163.8 (3)
C2—N1—C7A—C7−179.47 (5)C6—C7—C8—O2'−171.1 (18)
C2—N1—C10—C11−87.61 (6)C7—C7A—N1—C105.16 (9)
C2—N3—C3A—C4177.48 (5)C7—C8—O1—C9179.13 (6)
C2—N3—C3A—C7A−1.12 (6)C7A—N1—C10—C1187.20 (7)
C3A—C4—C5—C6−0.44 (8)C10—C11—C12—C13−174.93 (6)
C3A—C7A—C7—C6−0.92 (7)C10—C11—C12—C165.43 (7)
C3A—C7A—C7—C8176.33 (5)C10—C11—N4—C14176.03 (5)
C3A—C7A—N1—C10−176.57 (4)C11—C12—C13—N5−1.68 (7)
C4—C5—C6—C70.90 (8)C11—C12—C13—O3178.54 (5)
C5—C6—C7—C7A−0.18 (8)C11—N4—C14—N5−0.65 (7)
C5—C6—C7—C8−177.62 (6)C12—C13—N5—C14−0.16 (7)
C6—C7—C7A—N1177.14 (5)C12—C13—O3—C15−176.49 (6)
C6—C7—C8—O1−5.89 (6)C13—N5—C14—N41.46 (7)
 

Acknowledgements

We would like to thank Professor Christian W. Lehmann for providing access to the X-ray diffraction facility and Heike Schucht for technical assistance.

Funding information

Funding for this research was provided by: Deutsche Forschungsgemeinschaft (grant No. 432291016 to Adrian Richter); Mukoviszidose Institut gGmbH (Bonn, Germany), the research and development arm of the German Cystic Fibrosis Association Mukoviszidose e.V.; Open Access Publishing by the DFG.

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ISSN: 2414-3146
Volume 8| Part 1| January 2023| x230025
https://doi.org/10.1107/S2414314623000251