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Crystal structure of ethyl 4-[4-(di­methyl­amino)­phen­yl]-2,7,7-tri­methyl-5-oxo-1,4,5,6,7,8-hexa­hydro­quinoline-3-carboxyl­ate

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aDepartment of Biomedical and Pharmaceutical Sciences, The University of Montana, 32 Campus Drive, Missoula, MT 59812, USA, and bDepartment of Chemistry, Ithaca College, 953 Danby Road, Ithaca, NY 14850, USA
*Correspondence e-mail: nicholas.natale@mso.umt.edu

Edited by P. Dastidar, Indian Association for the Cultivation of Science, India (Received 31 July 2018; accepted 23 August 2018; online 11 September 2018)

In the title racemic compound, ethyl 4-(4-di­methyl­amino­phen­yl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa­hydro­quinoline-3-carboxyl­ate, the common structural features in this type of compound, such as the flat-boat conformation of the 1,4-di­hydro­pyridine (1,4-DHP) ring, the envelope conformation of the fused cyclo­hexa­none, and the substituted phenyl ring at the pseudo-axial position and orthogonal to the 1,4-DHP ring, are present. In the crystal, mol­ecules are linked via N—H⋯O and C—H⋯O hydrogen bonds, forming layers parallel to the (10[\overline1]) plane.

1. Chemical context

1,4-Di­hydro­pyridine (DHP) derivatives are well known for their calcium-channel blocking activity and many of these compounds, such as nifedipine, nicardipine, and amlodipine, have been used in the treatment of angina pectoris and systemic hypertension. (Wishart et al., 2006[Wishart, D. S., Knox, C., Guo, A. C., Shrivastava, S., Hassanali, M., Stothard, P., Chang, Z. & Woolsey, J. (2006). Nucleic Acids Res. 34, 668-672.]) 4-Aryl-1,4-di­hydro­pyridines that bind the L-type voltage-gated calcium channels (VGCC) have been in general medical practice for over three decades (Zamponi, 2005[Zamponi, G. (2005). Voltage-Gated Calcium Channels, pp. 327-337. New York: Landes Bioscience.]). Many modifications on 1,4-DHP have been performed to obtain active compounds as calcium-channel agonists or antagonists (Martín et al., 1995[Martín, N., Quinteiro, M., Seoane, C., Soto, J., Mora, A., Suárez, M., Ochoa, E., Morales, A. & Bosque, J. (1995). J. Heterocycl. Chem. 32, 235-238.]; Rose, 1990[Rose, U. (1990). Arch. Pharm. Pharm. Med. Chem. 323, 281-286.]; Rose & Dräger 1992[Rose, U. & Dräger, M. (1992). J. Med. Chem. 35, 2238-2243.]). One such modifications is fusing a cyclo­hexa­none ring to form hexa­hydro­quinolone, in which the orientation of the carbonyl group of the ester substituent at the 5-position in the 1,4-DHP ring has been fixed. This class of compounds has been shown to have moderate calcium-channel antagonistic activity, as well as anti-inflammatory modes and stem-cell differentiation properties, and has been implicated in slowing neurodegenerative disorders (Trippier et al., 2013[Trippier, P. C., Jansen Labby, K., Hawker, D., Mataka, J. & Silverman, R. (2013). J. Med. Chem. 56, 3121-3147.]). Recently, these compounds were found to have distinct selectivity profiles to different calcium channel subtypes (Schaller et al., 2018[Schaller, D., Gündüz, M. G., Zhang, F. X., Zamponi, G. W. & Wolber, G. (2018). Eur. J. Med. Chem. 155, 1-12.]). Another report also showed that the 4-aryl-hexa­hydro­quinolones, especially the ones containing a meth­oxy moiety, exhibit good anti­oxidant property as radical scavengers (Yang et al., 2011[Yang, X. H., Zhang, P. H., Zhou, Y. H., Liu, C. G., Lin, X. Y. & Cui, J. F. (2011). Arkivoc, x, 327-337.]). It has been revealed that the aryl group in the 4-position of the 1,4-DHP ring is the basic requirement for optimal activity and the type of electron-withdrawing groups on the phenyl group would affect the receptor-binding activity (Takahashi et al., 2008[Takahashi, D., Oyunzul, L., Onoue, S., Ito, Y., Uchida, S., Simsek, R., Gunduz, M. G., Safak, C. & Yamada, S. (2008). Biol. Pharm. Bull. 31, 473-479.]). It has also been proven that the flattened boat conformation of the 1,4-DHP ring is one factor that leads to higher calcium-channel activity (Linden et al., 2004[Linden, A., Şafak, C. & Aydın, F. (2004). Acta Cryst. C60, o711-o713.]). In a continuation of our study on the structure–activity relationship of this class of 1,4-DHP derivatives, i.e. 4-aryl-hexa­hydro­quinolones, we report herein the crystal structure of a compound we synthesized, ethyl 4-(4-di­methyl­amino­phen­yl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8- hexa­hydro­quinoline-3-carboxyl­ate.

[Scheme 1]

2. Structural commentary

The asymmetric unit of the title compound contains one independent mol­ecule crystallizing racemically in the monoclinic space group P21/n. A displacement ellipsoid plot showing the atomic numbering is presented in Fig. 1[link].

[Figure 1]
Figure 1
The asymmetric unit of the title compound showing the atom-labeling scheme. Displacement ellipsoids are drawn at the 50% probability level

In the title compound, the 1,4-DHP ring is characterized by a shallow or flattened boat conformation, which is one of the factors that leads to higher calcium-channel activity. The flattened boat conformation is visually obvious with the flat base formed by atoms C2, C3, C10, and C9 and the bow and stern formed by the slightly raised C4 and N1 atoms. The mean plane defined by atoms C2, C3, C9, and C10 is planar, with an r.m.s. deviation of 0.008 Å. The shallowness of the boat conformation is indicated by the marginal displacements of atoms N1 [0.1332 (15) Å] and C4 [0.3047 (16) Å] from this mean plane, and is also implied by the small puckering amplitude Q [0.2583 (10) Å].

Examination of the fused C5–C10 cyclo­hexa­none ring using puckering parameters also showed that the ring adopts an envelope conformation, with atom C7 protruding in the same direction as the 4-aryl group at a distance of 0.6453 (15) Å from the mean plane through the other five C atoms. The orientation of ring atom C7 makes the axial bond C7—C11 syn-periplanar to the 4-aryl group, i.e. the torsion angle between C7—C11 and C4—C17 is 6.91 (7)°.

The pseudo-axial position of the 4-aryl group is conserved in the title compound. The C17–C22 phenyl ring is almost orthogonal to the base of the 1,4-DHP ring formed by atoms C2, C3, C10, and C9, with the dihedral angles between the C2–C3–C10–C9 mean plane and the ring being 89.59 (3)°. The very small pseudo-torsion angle [2.44 (8)°] between N1—C4 and C17—C18 also implies a bis­ecting orientation of the 4-aryl group to the 1,4-DHP ring in this compound.

As in other 1,4-DHP compounds (Linden et al., 2004[Linden, A., Şafak, C. & Aydın, F. (2004). Acta Cryst. C60, o711-o713.]), the ester group is coplanar and at a cis orientation to the adjacent endocyclic C2=C3 double bond. The planarity extends out through the ester chains.

The nitro­gen atom in the di­methyl­amino group is almost in the same plane as the phenyl ring, at a distance of 0.0420 (16) Å from the mean plane. However, the plane formed by N2–C23–C24 is slightly bent from the phenyl group with the angle of 27.24 (11)° rather than being coplanar with the phenyl ring, which seems to be common in N,N-di­methyl­aniline type of compounds (Dahl, 2000[Dahl, T. (2000). Acta Cryst. C56, 708-710.]). In conclusion, the parameters reported here demonstrate that the conformational features usually observed in cyclo­hexa­none-fused 1,4-DHP derivatives have been conserved. As a promising base structure for calcium-channel antagonists, different substitutions and more structural modifications are being carried out in our group. Progress will be reported in due course.

3. Supra­molecular features

In the crystal, mol­ecules are linked along the diagonal of the ac plane by N—H⋯O hydrogen bonds, forming chains which are in turn linked by C—H⋯O hydrogen bonds into layers parallel to the (10[\overline1]) plane ­(see Fig. 2[link] and Table 1[link]).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N1—H1⋯O1i 0.879 (15) 1.968 (15) 2.8380 (11) 170.6 (14)
C13—H13C⋯O2ii 0.98 2.57 3.1741 (15) 120
Symmetry codes: (i) [x-{\script{1\over 2}}, -y+{\script{1\over 2}}, z-{\script{1\over 2}}]; (ii) -x, -y+1, -z+1.
[Figure 2]
Figure 2
A view normal to plane (10[\overline1]) of the crystal packing of the title compound. The hydrogen bonds (Table 1[link]) are shown as dashed lines and only H atoms H1 and H13C have been included.

4. Database survey

A search in the Cambridge Structural Database (Version 5.39, November 2017) for related compounds with a 4-aryl-hexa­hydro­quinolone-3-carboxyl­ate fragment gave 30 hits. All these compounds share the common structural features such as the flat-boat conformation of the1,4-di­hydro­pyridine (1,4-DHP) ring, the envelope conformation of the fused cyclo­hexa­none ring, and the substituted phenyl ring at the pseudo-axial position and orthogonal to the 1,4-DHP ring.

5. Synthesis and crystallization

An oven-dried 100 ml round-bottom flask equipped with a magnetic stir bar was charged with 10 mmol of dimedone, 10 mmol of ethyl aceto­acetate and 5 mol % of ytterbium(III) tri­fluoro­methane­sulfonate. The mixture was then taken up in 30 ml of absolute ethanol, capped and put under an inert atmosphere of argon, after which the solution was allowed to stir at room temperature for 20 min. The appropriate corresponding benzaldehyde (10 mmol) and 10 mmol of ammonium acetate were added to the stirring solution, the solution was allowed to stir at room temperature for 48 h. Reaction progress was monitored via TLC. Once the reaction was complete, excess solvent was removed via rotary evaporation. The solution was then purified via silica column chromatography. The title compound was recrystallized by slow evaporation from hexane and ethyl acetate (v:v = ?:?). m.p. 513.1 K.

1H NMR (δ, CDCl3) p.p.m. 0.95 (s, 3H), 1.05 (s, 3H), 1.22 (t, J = 7.08 Hz, 3H), 2.13 & 2.19 (ABq, 2H, J = 16.5 Hz), 2.17 & 2.27 (ABq, 2H, J = 16.5 Hz), 2.85 (s, 3H), 4.046 (q, J = 7.08 Hz, 2H), 4.94 (s, 1H), 6.06 (s, 1H), 6.57 (d, J = 6.8 Hz, 2H), 7.14 (d, J = 6.8 Hz, 2H).

13C NMR (δ, CDCl3) p.p.m. 14.37, 19.55, 27.42, 29.54, 32.82, 35.38, 40.86, 41.17, 50.85, 59.84, 106.61, 112.46, 128.70, 135.94, 142.95, 147.85, 149.06, 167.79, 195.75.

MS: calculated for C23H30N2O3, 382.49; observed: m/z = 405 ([M + 23] 7), 234 (100).

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. The H atoms on methyl groups were constrained to an ideal geometry, with C—H = 0.98 Å and Uiso(H) = 1.5Ueq(C), and were allowed to rotate freely about the C—C bonds. The rest of the H atoms were placed in calculated positions with C—H = 0.95–1.00 Å and refined as riding on their carrier atoms with Uiso(H) = 1.2Ueq(C). The positions of the amine H atoms and hydroxyl H atoms were determined from difference-Fourier maps and freely refined. Three low-angle reflections were omitted from the refinement because their observed intensities were much lower than the calculated values as a result of being partially obscured by the beam stop.

Table 2
Experimental details

Crystal data
Chemical formula C23H30N2O3
Mr 382.49
Crystal system, space group Monoclinic, P21/n
Temperature (K) 100
a, b, c (Å) 9.6834 (3), 18.2390 (5), 12.2073 (3)
β (°) 105.4464 (14)
V3) 2078.12 (10)
Z 4
Radiation type Mo Kα
μ (mm−1) 0.08
Crystal size (mm) 0.46 × 0.30 × 0.26
 
Data collection
Diffractometer Bruker SMART BREEZE CCD
Absorption correction Multi-scan (SADABS; Bruker, 2013[Bruker (2013). APEX2, SAINT and SADABS. Bruker AXS ins., Madison, Wisconsin, USA.])
Tmin, Tmax 0.923, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections 48649, 7211, 5703
Rint 0.038
(sin θ/λ)max−1) 0.747
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.049, 0.142, 1.02
No. of reflections 7211
No. of parameters 264
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.56, −0.21
Computer programs: APEX2 and SAINT (Bruker, 2013[Bruker (2013). APEX2, SAINT and SADABS. Bruker AXS ins., Madison, Wisconsin, USA.]), SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), SHELXL2014 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]) and 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.]).

Supporting information


Computing details top

Data collection: APEX2 (Bruker, 2013); cell refinement: SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

Ethyl 4-[4-(dimethylamino)phenyl]-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate top
Crystal data top
C23H30N2O3Dx = 1.223 Mg m3
Mr = 382.49Melting point: 240.1 K
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
a = 9.6834 (3) ÅCell parameters from 9940 reflections
b = 18.2390 (5) Åθ = 2.5–31.8°
c = 12.2073 (3) ŵ = 0.08 mm1
β = 105.4464 (14)°T = 100 K
V = 2078.12 (10) Å3Prism, yellow
Z = 40.46 × 0.30 × 0.26 mm
F(000) = 824
Data collection top
Bruker SMART BREEZE CCD
diffractometer
5703 reflections with I > 2σ(I)
Radiation source: 2 kW sealed X-ray tubeRint = 0.038
φ and ω scansθmax = 32.1°, θmin = 2.4°
Absorption correction: multi-scan
(SADABS; Bruker, 2013)
h = 1314
Tmin = 0.923, Tmax = 1.000k = 2727
48649 measured reflectionsl = 1818
7211 independent reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullHydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.049H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.142 w = 1/[σ2(Fo2) + (0.0858P)2 + 0.4034P]
where P = (Fo2 + 2Fc2)/3
S = 1.02(Δ/σ)max < 0.001
7211 reflectionsΔρmax = 0.56 e Å3
264 parametersΔρmin = 0.21 e Å3
0 restraints
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
O10.56627 (8)0.18519 (4)0.65486 (6)0.02329 (16)
O20.20382 (10)0.48113 (4)0.62250 (7)0.0315 (2)
O30.32826 (8)0.40562 (4)0.75768 (6)0.02233 (16)
N10.18215 (9)0.30161 (5)0.39338 (7)0.01757 (16)
N20.02043 (10)0.12538 (5)0.88241 (7)0.02398 (19)
C20.17423 (10)0.35953 (5)0.46481 (8)0.01733 (18)
C30.25415 (10)0.35787 (5)0.57458 (8)0.01643 (17)
C40.33616 (10)0.28901 (5)0.62517 (7)0.01576 (17)
H40.42960.30450.67760.019*
C50.48613 (10)0.19197 (5)0.55790 (8)0.01629 (17)
C60.51589 (10)0.14782 (6)0.46162 (8)0.01877 (18)
H6A0.56260.10120.49280.023*
H6B0.58420.17540.42970.023*
C70.38262 (11)0.13022 (6)0.36546 (8)0.01950 (19)
C80.30521 (11)0.20264 (6)0.32603 (8)0.01878 (18)
H8A0.36030.23060.28240.023*
H8B0.20980.19190.27440.023*
C90.28658 (10)0.24911 (5)0.42229 (8)0.01549 (17)
C100.36785 (10)0.24286 (5)0.53149 (7)0.01521 (17)
C110.28490 (13)0.07753 (6)0.40759 (11)0.0284 (2)
H11A0.25890.09930.47270.043*
H11B0.33530.03110.43060.043*
H11C0.19790.06840.34640.043*
C120.42649 (14)0.09541 (8)0.26599 (10)0.0327 (3)
H12A0.47410.04840.29010.049*
H12B0.49240.12820.24120.049*
H12C0.34110.08720.20290.049*
C130.07190 (12)0.41868 (6)0.40825 (9)0.0234 (2)
H13A0.02210.40340.33090.035*
H13B0.12520.46400.40530.035*
H13C0.00170.42730.45170.035*
C140.25628 (11)0.42135 (5)0.64921 (8)0.01880 (18)
C150.32585 (12)0.46169 (6)0.84080 (9)0.0225 (2)
H15A0.22680.47920.83230.027*
H15B0.38600.50390.83160.027*
C160.38454 (12)0.42620 (6)0.95533 (9)0.0232 (2)
H16A0.32670.38310.96140.035*
H16B0.38110.46131.01530.035*
H16C0.48400.41120.96370.035*
C170.25404 (10)0.24552 (5)0.69388 (8)0.01645 (17)
C180.12125 (11)0.21446 (6)0.64193 (8)0.02084 (19)
H180.08180.22080.56250.025*
C190.04507 (12)0.17457 (6)0.70303 (8)0.0224 (2)
H190.04520.15430.66480.027*
C200.09936 (11)0.16371 (5)0.82071 (8)0.01958 (19)
C210.23303 (11)0.19489 (6)0.87312 (8)0.0213 (2)
H210.27330.18840.95240.026*
C220.30727 (11)0.23512 (6)0.81049 (8)0.01973 (19)
H220.39700.25610.84840.024*
C230.08672 (14)0.07366 (7)0.82229 (10)0.0311 (2)
H23A0.1338 (9)0.0513 (5)0.8755 (5)0.047*
H23B0.0408 (5)0.0356 (5)0.7881 (8)0.047*
H23C0.1578 (9)0.0993 (3)0.7628 (8)0.047*
C240.09169 (14)0.10629 (7)0.99913 (9)0.0295 (2)
H24A0.02390.08121.03330.044*
H24B0.12650.15101.04220.044*
H24C0.17280.07381.00070.044*
H10.1367 (16)0.3063 (8)0.3211 (13)0.029 (4)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0214 (3)0.0261 (4)0.0175 (3)0.0058 (3)0.0032 (3)0.0014 (3)
O20.0422 (5)0.0195 (4)0.0272 (4)0.0107 (3)0.0006 (3)0.0023 (3)
O30.0275 (4)0.0178 (3)0.0185 (3)0.0034 (3)0.0006 (3)0.0048 (2)
N10.0173 (4)0.0179 (4)0.0144 (3)0.0033 (3)0.0012 (3)0.0002 (3)
N20.0277 (5)0.0273 (5)0.0197 (4)0.0008 (4)0.0111 (3)0.0017 (3)
C20.0162 (4)0.0156 (4)0.0188 (4)0.0010 (3)0.0021 (3)0.0005 (3)
C30.0162 (4)0.0149 (4)0.0170 (4)0.0013 (3)0.0024 (3)0.0007 (3)
C40.0160 (4)0.0153 (4)0.0139 (4)0.0011 (3)0.0004 (3)0.0007 (3)
C50.0149 (4)0.0160 (4)0.0166 (4)0.0001 (3)0.0019 (3)0.0002 (3)
C60.0150 (4)0.0217 (4)0.0185 (4)0.0032 (3)0.0024 (3)0.0015 (3)
C70.0174 (4)0.0210 (4)0.0184 (4)0.0027 (3)0.0019 (3)0.0040 (3)
C80.0191 (4)0.0215 (4)0.0141 (4)0.0026 (3)0.0016 (3)0.0018 (3)
C90.0146 (4)0.0156 (4)0.0153 (4)0.0004 (3)0.0023 (3)0.0008 (3)
C100.0154 (4)0.0147 (4)0.0143 (4)0.0006 (3)0.0019 (3)0.0004 (3)
C110.0264 (5)0.0193 (5)0.0365 (6)0.0039 (4)0.0034 (4)0.0031 (4)
C120.0304 (6)0.0408 (7)0.0234 (5)0.0129 (5)0.0013 (4)0.0119 (4)
C130.0216 (5)0.0202 (5)0.0244 (5)0.0064 (4)0.0008 (4)0.0019 (4)
C140.0173 (4)0.0180 (4)0.0199 (4)0.0006 (3)0.0027 (3)0.0015 (3)
C150.0243 (5)0.0191 (4)0.0227 (4)0.0003 (4)0.0036 (4)0.0073 (3)
C160.0222 (5)0.0260 (5)0.0215 (4)0.0034 (4)0.0059 (4)0.0051 (4)
C170.0186 (4)0.0153 (4)0.0146 (4)0.0022 (3)0.0028 (3)0.0015 (3)
C180.0236 (5)0.0236 (5)0.0140 (4)0.0035 (4)0.0028 (3)0.0013 (3)
C190.0242 (5)0.0256 (5)0.0174 (4)0.0043 (4)0.0055 (4)0.0021 (3)
C200.0242 (5)0.0181 (4)0.0181 (4)0.0033 (4)0.0087 (4)0.0001 (3)
C210.0237 (5)0.0252 (5)0.0143 (4)0.0044 (4)0.0037 (3)0.0016 (3)
C220.0192 (4)0.0220 (5)0.0157 (4)0.0026 (3)0.0007 (3)0.0001 (3)
C230.0338 (6)0.0328 (6)0.0318 (6)0.0069 (5)0.0173 (5)0.0015 (4)
C240.0344 (6)0.0346 (6)0.0225 (5)0.0059 (5)0.0129 (4)0.0078 (4)
Geometric parameters (Å, º) top
O1—C51.2367 (11)C11—H11B0.9800
O2—C141.2103 (12)C11—H11C0.9800
O3—C141.3527 (12)C12—H12A0.9800
O3—C151.4451 (12)C12—H12B0.9800
N1—C21.3849 (12)C12—H12C0.9800
N1—C91.3690 (12)C13—H13A0.9800
N1—H10.879 (15)C13—H13B0.9800
N2—C201.3953 (13)C13—H13C0.9800
N2—C231.4489 (16)C15—H15A0.9900
N2—C241.4505 (14)C15—H15B0.9900
C2—C31.3575 (12)C15—C161.5078 (15)
C2—C131.5028 (13)C16—H16A0.9800
C3—C41.5259 (13)C16—H16B0.9800
C3—C141.4700 (13)C16—H16C0.9800
C4—H41.0000C17—C181.3936 (14)
C4—C101.5157 (13)C17—C221.3917 (13)
C4—C171.5233 (13)C18—H180.9500
C5—C61.5143 (13)C18—C191.3867 (14)
C5—C101.4425 (13)C19—H190.9500
C6—H6A0.9900C19—C201.4061 (14)
C6—H6B0.9900C20—C211.4024 (15)
C6—C71.5296 (13)C21—H210.9500
C7—C81.5317 (14)C21—C221.3903 (14)
C7—C111.5306 (16)C22—H220.9500
C7—C121.5272 (15)C23—H23A0.976 (10)
C8—H8A0.9900C23—H23B0.976 (10)
C8—H8B0.9900C23—H23C0.976 (10)
C8—C91.4982 (13)C24—H24A0.9800
C9—C101.3603 (12)C24—H24B0.9800
C11—H11A0.9800C24—H24C0.9800
C14—O3—C15115.89 (8)H12A—C12—H12B109.5
C2—N1—H1117.4 (10)H12A—C12—H12C109.5
C9—N1—C2122.15 (8)H12B—C12—H12C109.5
C9—N1—H1117.7 (10)C2—C13—H13A109.5
C20—N2—C23118.30 (9)C2—C13—H13B109.5
C20—N2—C24117.70 (10)C2—C13—H13C109.5
C23—N2—C24115.49 (9)H13A—C13—H13B109.5
N1—C2—C13113.49 (8)H13A—C13—H13C109.5
C3—C2—N1119.47 (8)H13B—C13—H13C109.5
C3—C2—C13127.03 (9)O2—C14—O3121.65 (9)
C2—C3—C4121.07 (8)O2—C14—C3127.36 (9)
C2—C3—C14120.30 (9)O3—C14—C3110.99 (8)
C14—C3—C4118.53 (8)O3—C15—H15A110.5
C3—C4—H4108.1O3—C15—H15B110.5
C10—C4—C3109.87 (7)O3—C15—C16105.94 (8)
C10—C4—H4108.1H15A—C15—H15B108.7
C10—C4—C17111.50 (7)C16—C15—H15A110.5
C17—C4—C3111.08 (8)C16—C15—H15B110.5
C17—C4—H4108.1C15—C16—H16A109.5
O1—C5—C6119.28 (8)C15—C16—H16B109.5
O1—C5—C10122.46 (9)C15—C16—H16C109.5
C10—C5—C6118.20 (8)H16A—C16—H16B109.5
C5—C6—H6A108.7H16A—C16—H16C109.5
C5—C6—H6B108.7H16B—C16—H16C109.5
C5—C6—C7114.28 (8)C18—C17—C4120.98 (8)
H6A—C6—H6B107.6C22—C17—C4121.92 (9)
C7—C6—H6A108.7C22—C17—C18117.10 (9)
C7—C6—H6B108.7C17—C18—H18119.1
C6—C7—C8107.60 (8)C19—C18—C17121.80 (9)
C6—C7—C11110.16 (9)C19—C18—H18119.1
C11—C7—C8110.63 (9)C18—C19—H19119.5
C12—C7—C6109.94 (9)C18—C19—C20121.05 (10)
C12—C7—C8108.97 (9)C20—C19—H19119.5
C12—C7—C11109.50 (9)N2—C20—C19120.83 (10)
C7—C8—H8A109.0N2—C20—C21121.91 (9)
C7—C8—H8B109.0C21—C20—C19117.22 (9)
H8A—C8—H8B107.8C20—C21—H21119.6
C9—C8—C7113.11 (8)C22—C21—C20120.85 (9)
C9—C8—H8A109.0C22—C21—H21119.6
C9—C8—H8B109.0C17—C22—H22119.0
N1—C9—C8115.37 (8)C21—C22—C17121.97 (9)
C10—C9—N1120.40 (8)C21—C22—H22119.0
C10—C9—C8124.20 (8)N2—C23—H23A109.5
C5—C10—C4119.80 (8)N2—C23—H23B109.5
C9—C10—C4120.82 (8)N2—C23—H23C109.5
C9—C10—C5119.38 (8)H23A—C23—H23B109.5
C7—C11—H11A109.5H23A—C23—H23C109.4
C7—C11—H11B109.5H23B—C23—H23C109.5
C7—C11—H11C109.5N2—C24—H24A109.5
H11A—C11—H11B109.5N2—C24—H24B109.5
H11A—C11—H11C109.5N2—C24—H24C109.5
H11B—C11—H11C109.5H24A—C24—H24B109.5
C7—C12—H12A109.5H24A—C24—H24C109.5
C7—C12—H12B109.5H24B—C24—H24C109.5
C7—C12—H12C109.5
O1—C5—C6—C7151.47 (9)C8—C9—C10—C4176.32 (9)
O1—C5—C10—C41.56 (14)C8—C9—C10—C54.11 (14)
O1—C5—C10—C9178.01 (9)C9—N1—C2—C312.50 (14)
N1—C2—C3—C48.68 (14)C9—N1—C2—C13168.16 (9)
N1—C2—C3—C14175.02 (9)C10—C4—C17—C1859.06 (11)
N1—C9—C10—C45.51 (14)C10—C4—C17—C22121.10 (10)
N1—C9—C10—C5174.06 (9)C10—C5—C6—C731.05 (12)
N2—C20—C21—C22177.63 (9)C11—C7—C8—C972.35 (11)
C2—N1—C9—C8164.12 (9)C12—C7—C8—C9167.21 (9)
C2—N1—C9—C1014.20 (14)C13—C2—C3—C4170.56 (10)
C2—C3—C4—C1024.82 (12)C13—C2—C3—C145.74 (16)
C2—C3—C4—C1799.03 (10)C14—O3—C15—C16168.44 (9)
C2—C3—C14—O27.65 (17)C14—C3—C4—C10158.81 (8)
C2—C3—C14—O3172.85 (9)C14—C3—C4—C1777.33 (11)
C3—C4—C10—C5156.41 (8)C15—O3—C14—O26.08 (15)
C3—C4—C10—C923.16 (12)C15—O3—C14—C3174.38 (8)
C3—C4—C17—C1863.85 (11)C17—C4—C10—C579.98 (10)
C3—C4—C17—C22115.98 (10)C17—C4—C10—C9100.45 (10)
C4—C3—C14—O2175.96 (11)C17—C18—C19—C200.10 (16)
C4—C3—C14—O33.55 (12)C18—C17—C22—C210.74 (15)
C4—C17—C18—C19179.87 (9)C18—C19—C20—N2178.09 (10)
C4—C17—C22—C21179.42 (9)C18—C19—C20—C210.06 (15)
C5—C6—C7—C853.46 (11)C19—C20—C21—C220.38 (15)
C5—C6—C7—C1167.23 (11)C20—C21—C22—C170.81 (16)
C5—C6—C7—C12172.01 (9)C22—C17—C18—C190.29 (15)
C6—C5—C10—C4178.95 (8)C23—N2—C20—C1923.89 (15)
C6—C5—C10—C90.63 (13)C23—N2—C20—C21158.17 (10)
C6—C7—C8—C948.04 (11)C24—N2—C20—C19170.49 (10)
C7—C8—C9—N1160.24 (8)C24—N2—C20—C2111.57 (15)
C7—C8—C9—C1021.50 (14)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.879 (15)1.968 (15)2.8380 (11)170.6 (14)
C13—H13C···O2ii0.982.573.1741 (15)120
Symmetry codes: (i) x1/2, y+1/2, z1/2; (ii) x, y+1, z+1.
 

Acknowledgements

We would like to thank Dr David J. Burkhart of the Center for Translational Medicine at the University of Montana for the mass spectrometry. We thank Dr Robert Zipkin of MedChem101 for funds to support the publication costs of this article.

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