organic compounds
3-{3,5-Bis[(2-butoxyethoxy)carbonyl]-2,6-dimethyl-1,4-dihydropyridin-4-yl}-1-[(3,4,5-trimethoxybenzoyl)methyl]pyridinium bromide
aLatvian Institute of Organic Synthesis, 21 Aizkraukles Street, Riga LV-1006, Latvia
*Correspondence e-mail: mishnevs@osi.lv
In the title salt, C37H51N2O10+·Br−, the 1,4-dihydropyridine (1,4-DHP) ring adopts a slighly puckered boat conformation. The N and opposite C atoms deviate from the least-squares plane calculated through the four other ring atoms by 0.068 (5) and 0.224 (5) Å, respectively. The orientation of both C=O groups is similar (cis with respect to the double bonds of 1,4-DHP. The pyridinium ring has an axial orientation with respect to the1,4-DHP ring and is almost perpendicular to the least-squares plane of the 1,4-DHP ring, making a dihedral angle of 89.2 (3)°. The molecule has a compact shape due to the parallel orientation of the long-chain substituents. One of the butoxy groups was fond to be disordered (occupancy ratio 0.70:0.30). In the crystal, the bromide anion accepts a weak hydrogen bond from the N—H group of a neighboring 1,4-DHP ring.
Related literature
For general information on the relationship between 1,4-dihydropyridine ring substituents and pharmaceutical effects, see: Hasko & Pacher (2008); Niebauer & Robinson (2006); Ruiz et al. (2012); Swarnalatha et al. (2011). For the synthesis of the DHP 3-pyridyl derivative, see: Saini et al. (2008).
Experimental
Crystal data
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Data collection
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Refinement
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Data collection: COLLECT (Hooft, 1998); cell SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO (Otwinowski & Minor, 1997) and SCALEPACK; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 2012); software used to prepare material for publication: SHELXL97.
Supporting information
https://doi.org/10.1107/S1600536812049896/vm2184sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536812049896/vm2184Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S1600536812049896/vm2184Isup3.cml
First the DHP 3-pyridyl derivative was obtained by means of the Hantzsch method as described by Saini et al. (2008). After the structure confirmation the intermediate (1 mmol) was added to α-bromo-(3,4,5-trimethoxy)-acetophenone (1 mmol) in 30 ml acetone. Reaction mixture was boiled for 24 h, and after completion (monitored by TLC) cooled to ambient temperature. This procedure gives the title compound pyridinium salt as block crystals, suitable for X-ray analysis. 1H-NMR (400 MHz, DMSO-d6), δ/p.p.m.: 9.08 (m, 1H, py-2-H), 8.78–8.82 (m, 1H, py-6-H), 8.46 (d, 1H, J=8.0 Hz, py-4-H), 7.71–7.77(m, 2H, py-5-H and N—H), 7.46 (s, 2H, Ph-2,6-H), 6.95 (m, 2H, N+CH2), 5.16(s, 1H, 4-H), 4.17 (t, 4H, J=4.8 Hz, COOCH2CH2), 3.98 (s, 6H,Ar—H), 3.92 (s, 3H, Ar-4-OCH3), 3.52–3.62 (m, 4H, 3,5-COOCH2CH2),3.36–3.45 (m, 4H, 3,5-CH2CH2CH2CH3), 2.46 (s, 6H, 2,6-CH3),1.46–1.53(m, 4H, 3,5-CH2CH2CH2CH3), 1.25–1,35 (m, 4H,3,5-CH2CH2CH2CH3), 0.85–0.89 (t, 6H, J=7.6 Hz,3,5-CH2CH2CH2CH3); MS (ESI) m/z: 684 [M—Br]+; Anal. Calcd for C37H51BrN2O10: C, 58.19; H, 6.73; N, 3.67; found: C, 58.11; H, 6.76; N, 3.61.
The H-atoms were included in the
at calculated positions (N—H = 0.86 Å, C—H = 0.93 to 0.98 Å) and treated using a riding-model approximation as implemented in SHELXL97 software. Disorder was detected in the butoxy group with occupancies of 0.7 for atoms C28, C29, C30 and C31 and 0.3 for C28B, C29B, C30B and C31B. The maximum difference density is rather high (1.15 e Å-3) because of Fourier series truncation errors expected for a structure containing a heavy atom Br.Nowadays considerable attention is paid to the synthesis of 1,4-dihydropyridine (1,4-DHP) derivatives because of their wide spectrum of biological activity. Slight variations in 1,4-DHP ring substituents can result in considerable changes in pharmacological effects (Swarnalatha et al., 2011). 1,4-Dihydropyridines are considered as privileged structures, because these compounds are capable to bind to multiple receptors with high affinity (Ruiz et al., 2012).
It was found that the concentration of adenosine, the natural ligand of the A2A receptor, changes in the ischemia, hypoxia and inflammation conditions (Hasko & Pacher, 2008). The A2A receptor is believed to play a role in cardioprotection, inflammation, stroke and certain central nervous system disorders (Niebauer & Robinson, 2006). We were looking for molecules based on 1,4-DHP able to bind A2A adenosine receptors and possessing enhanced water solubility.
Fig. 1 shows a view of the
of the title compound. For the disordered butoxy fragment only atoms with the higher occupation factor are shown. In the the 1,4-DHP ring adopts a slightly puckered boat conformation. Atoms N1 and C4 deviate from the least-squares plane calculated through the four other ring atoms by 0.068 (5) Å and 0.224 (5) Å, respectively. The orientation of both C=O groups is cis with respect to the double bonds of 1,4-DHP. The pyridinium ring has an axial orientation with respect to the 1,4-DHP ring and is almost perpendicular to the least-squares average plane of the 1,4-DHP ring with a dihedral angle between both planes of 89.2 (3)°. The molecule has a compact shape with all long chain substituents oriented approximately in one direction. All bonds in the substituents at the 3 and 5 position of 1,4-DHP have trans orientation except for bonds C29B—C30B and C33—C34 (gauche-). The bromine anion forms a weak hydrogen bond with N1—H1 of a neighboring 1,4-DHP ring. The distance between the bromine ion and the positively charged N2 atom is 4.185 (5) Å.For general information on the relationship between 1,4-dihydropyridine ring substituents and pharmaceutical effects, see: Hasko & Pacher (2008); Niebauer & Robinson (2006); Ruiz et al. (2012); Swarnalatha et al. (2011). For the synthesis of the DHP 3-pyridyl derivative, see: Saini et al. (2008).
Data collection: COLLECT (Hooft, 1998); cell
SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO and SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 2012); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).C37H51N2O10+·Br− | Z = 2 |
Mr = 763.71 | F(000) = 804 |
Triclinic, P1 | Dx = 1.353 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 8.9501 (2) Å | Cell parameters from 20441 reflections |
b = 12.4741 (3) Å | θ = 1.0–27.9° |
c = 17.6994 (5) Å | µ = 1.16 mm−1 |
α = 93.057 (1)° | T = 190 K |
β = 91.658 (1)° | Block, colourless |
γ = 108.024 (1)° | 0.32 × 0.18 × 0.16 mm |
V = 1874.25 (8) Å3 |
Nonius KappaCCD diffractometer | 6509 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.035 |
Graphite monochromator | θmax = 27.8°, θmin = 2.1° |
CCD scans | h = −11→11 |
13618 measured reflections | k = −16→16 |
8822 independent reflections | l = −23→23 |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.056 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.127 | H-atom parameters constrained |
S = 1.03 | w = 1/[σ2(Fo2) + (0.040P)2 + 2.P] where P = (Fo2 + 2Fc2)/3 |
8822 reflections | (Δ/σ)max = 0.001 |
469 parameters | Δρmax = 1.15 e Å−3 |
4 restraints | Δρmin = −0.41 e Å−3 |
C37H51N2O10+·Br− | γ = 108.024 (1)° |
Mr = 763.71 | V = 1874.25 (8) Å3 |
Triclinic, P1 | Z = 2 |
a = 8.9501 (2) Å | Mo Kα radiation |
b = 12.4741 (3) Å | µ = 1.16 mm−1 |
c = 17.6994 (5) Å | T = 190 K |
α = 93.057 (1)° | 0.32 × 0.18 × 0.16 mm |
β = 91.658 (1)° |
Nonius KappaCCD diffractometer | 6509 reflections with I > 2σ(I) |
13618 measured reflections | Rint = 0.035 |
8822 independent reflections |
R[F2 > 2σ(F2)] = 0.056 | 4 restraints |
wR(F2) = 0.127 | H-atom parameters constrained |
S = 1.03 | Δρmax = 1.15 e Å−3 |
8822 reflections | Δρmin = −0.41 e Å−3 |
469 parameters |
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. |
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. |
x | y | z | Uiso*/Ueq | Occ. (<1) | |
Br1 | 0.37986 (4) | 0.16649 (2) | 0.524390 (18) | 0.03630 (11) | |
O5 | −0.0812 (2) | 0.54844 (16) | 0.61743 (11) | 0.0294 (4) | |
O6 | −0.1497 (2) | 0.35179 (17) | 0.69842 (12) | 0.0354 (5) | |
N2 | 0.2738 (3) | 0.43048 (18) | 0.64368 (12) | 0.0233 (5) | |
O8 | 0.2588 (3) | 0.03534 (18) | 0.93630 (12) | 0.0410 (5) | |
O4 | −0.1071 (2) | 0.62698 (18) | 0.50837 (12) | 0.0377 (5) | |
O10 | −0.0811 (3) | −0.10148 (19) | 0.72532 (13) | 0.0512 (6) | |
O2 | 0.2910 (3) | 0.71278 (18) | 0.81572 (11) | 0.0362 (5) | |
N1 | 0.2834 (3) | 0.90617 (19) | 0.59677 (14) | 0.0310 (5) | |
H1 | 0.3253 | 0.9628 | 0.5704 | 0.037* | |
O9 | 0.0265 (3) | −0.12535 (18) | 0.86279 (13) | 0.0474 (6) | |
O1 | 0.4524 (3) | 0.8906 (2) | 0.82333 (13) | 0.0491 (6) | |
C32 | −0.0378 (3) | 0.6335 (2) | 0.56916 (15) | 0.0264 (6) | |
O7 | 0.4044 (3) | 0.3582 (2) | 0.75908 (14) | 0.0528 (7) | |
C10 | 0.4047 (3) | 0.6509 (2) | 0.61258 (15) | 0.0263 (6) | |
H10 | 0.4495 | 0.7258 | 0.6015 | 0.032* | |
C13 | 0.2062 (3) | 0.5076 (2) | 0.66831 (15) | 0.0243 (6) | |
H13 | 0.1170 | 0.4854 | 0.6965 | 0.029* | |
C4 | 0.1812 (3) | 0.7049 (2) | 0.67322 (15) | 0.0243 (6) | |
H4 | 0.1025 | 0.6725 | 0.7099 | 0.029* | |
C5 | 0.0976 (3) | 0.7251 (2) | 0.60136 (15) | 0.0248 (6) | |
C14 | 0.2046 (3) | 0.3118 (2) | 0.66100 (16) | 0.0264 (6) | |
H14A | 0.2135 | 0.2628 | 0.6181 | 0.032* | |
H14B | 0.0939 | 0.2967 | 0.6701 | 0.032* | |
C6 | 0.1559 (3) | 0.8212 (2) | 0.56498 (16) | 0.0279 (6) | |
C16 | 0.2225 (3) | 0.1752 (2) | 0.76203 (16) | 0.0285 (6) | |
C12 | 0.4066 (3) | 0.4596 (2) | 0.60494 (15) | 0.0261 (6) | |
H12 | 0.4516 | 0.4050 | 0.5887 | 0.031* | |
C11 | 0.4746 (3) | 0.5706 (2) | 0.58965 (16) | 0.0277 (6) | |
H11 | 0.5674 | 0.5918 | 0.5640 | 0.033* | |
C15 | 0.2887 (3) | 0.2872 (2) | 0.73052 (17) | 0.0309 (6) | |
C9 | 0.2681 (3) | 0.6197 (2) | 0.65203 (14) | 0.0229 (5) | |
C33 | −0.1872 (3) | 0.4421 (2) | 0.58642 (17) | 0.0312 (6) | |
H33A | −0.1295 | 0.4009 | 0.5576 | 0.037* | |
H33B | −0.2663 | 0.4550 | 0.5527 | 0.037* | |
C2 | 0.3479 (3) | 0.9060 (2) | 0.66820 (16) | 0.0283 (6) | |
C21 | 0.1014 (3) | 0.0893 (2) | 0.72309 (17) | 0.0304 (6) | |
H21 | 0.0643 | 0.0996 | 0.6753 | 0.036* | |
O3 | 0.3297 (3) | 0.5876 (3) | 0.98920 (14) | 0.0642 (8) | |
C17 | 0.2812 (3) | 0.1598 (2) | 0.83288 (17) | 0.0310 (6) | |
H17 | 0.3636 | 0.2168 | 0.8576 | 0.037* | |
C34 | −0.2639 (3) | 0.3750 (3) | 0.64977 (18) | 0.0346 (7) | |
H34A | −0.3208 | 0.4167 | 0.6785 | 0.041* | |
H34B | −0.3389 | 0.3045 | 0.6294 | 0.041* | |
C7 | 0.0949 (4) | 0.8480 (3) | 0.49096 (17) | 0.0372 (7) | |
H7A | 0.1144 | 0.7999 | 0.4509 | 0.056* | |
H7B | 0.1474 | 0.9255 | 0.4818 | 0.056* | |
H7C | −0.0162 | 0.8359 | 0.4928 | 0.056* | |
C19 | 0.0922 (4) | −0.0265 (2) | 0.82862 (17) | 0.0358 (7) | |
C25 | 0.3563 (4) | 0.8138 (3) | 0.78638 (17) | 0.0326 (6) | |
C20 | 0.0376 (4) | −0.0115 (2) | 0.75696 (17) | 0.0352 (7) | |
C3 | 0.2964 (3) | 0.8140 (2) | 0.70859 (15) | 0.0269 (6) | |
C8 | 0.4740 (4) | 1.0140 (2) | 0.69322 (19) | 0.0386 (7) | |
H8A | 0.4357 | 1.0542 | 0.7319 | 0.058* | |
H8B | 0.5024 | 1.0598 | 0.6508 | 0.058* | |
H8C | 0.5647 | 0.9972 | 0.7129 | 0.058* | |
C26 | 0.3417 (4) | 0.7075 (3) | 0.89303 (17) | 0.0438 (8) | |
H26A | 0.3135 | 0.7627 | 0.9255 | 0.053* | |
H26B | 0.4550 | 0.7240 | 0.8971 | 0.053* | |
C18 | 0.2157 (4) | 0.0586 (3) | 0.86639 (16) | 0.0323 (6) | |
C24 | −0.1484 (4) | −0.0902 (3) | 0.65342 (19) | 0.0461 (8) | |
H24A | −0.1965 | −0.0314 | 0.6577 | 0.069* | |
H24B | −0.2264 | −0.1602 | 0.6366 | 0.069* | |
H24C | −0.0675 | −0.0715 | 0.6174 | 0.069* | |
C36 | −0.1104 (4) | 0.2827 (3) | 0.81904 (19) | 0.0467 (9) | |
H36A | −0.0652 | 0.3591 | 0.8414 | 0.056* | |
H36B | −0.0256 | 0.2582 | 0.7991 | 0.056* | |
C22 | 0.3969 (4) | 0.1114 (3) | 0.9727 (2) | 0.0550 (10) | |
H22A | 0.4852 | 0.1150 | 0.9423 | 0.083* | |
H22B | 0.4143 | 0.0857 | 1.0213 | 0.083* | |
H22C | 0.3849 | 0.1852 | 0.9791 | 0.083* | |
C23 | −0.1099 (5) | −0.1226 (3) | 0.9026 (2) | 0.0635 (12) | |
H23A | −0.1531 | −0.1927 | 0.9258 | 0.095* | |
H23B | −0.1872 | −0.1118 | 0.8676 | 0.095* | |
H23C | −0.0808 | −0.0615 | 0.9409 | 0.095* | |
C35 | −0.2229 (4) | 0.2823 (3) | 0.7565 (2) | 0.0519 (9) | |
H32A | −0.2704 | 0.2055 | 0.7352 | 0.062* | |
H32B | −0.3060 | 0.3089 | 0.7763 | 0.062* | |
C27 | 0.2631 (5) | 0.5922 (3) | 0.9163 (2) | 0.0582 (10) | |
H27A | 0.1505 | 0.5784 | 0.9182 | 0.070* | |
H27B | 0.2819 | 0.5362 | 0.8810 | 0.070* | |
C37 | −0.1891 (6) | 0.2048 (5) | 0.8804 (3) | 0.0757 (13) | |
H37A | −0.2754 | 0.2289 | 0.8989 | 0.091* | |
H37B | −0.2336 | 0.1288 | 0.8574 | 0.091* | |
C38 | −0.0868 (6) | 0.2013 (5) | 0.9449 (3) | 0.0794 (14) | |
H38A | −0.1465 | 0.1517 | 0.9804 | 0.119* | |
H38B | −0.0429 | 0.2759 | 0.9688 | 0.119* | |
H38C | −0.0035 | 0.1741 | 0.9279 | 0.119* | |
C28 | 0.2319 (8) | 0.5017 (5) | 1.0321 (3) | 0.0560 (15) | 0.70 |
H28A | 0.1895 | 0.4332 | 0.9995 | 0.067* | 0.70 |
H28B | 0.1442 | 0.5254 | 1.0490 | 0.067* | 0.70 |
C29 | 0.3162 (9) | 0.4762 (6) | 1.0992 (3) | 0.0622 (18) | 0.70 |
H29A | 0.3861 | 0.5469 | 1.1224 | 0.075* | 0.70 |
H29B | 0.3811 | 0.4313 | 1.0818 | 0.075* | 0.70 |
C30 | 0.2131 (9) | 0.4145 (6) | 1.1593 (4) | 0.0618 (18) | 0.70 |
H30A | 0.1629 | 0.4647 | 1.1840 | 0.074* | 0.70 |
H30B | 0.1310 | 0.3505 | 1.1353 | 0.074* | 0.70 |
C31 | 0.3027 (7) | 0.3732 (4) | 1.2181 (3) | 0.0540 (14) | 0.70 |
H31A | 0.2320 | 0.3353 | 1.2550 | 0.081* | 0.70 |
H31B | 0.3832 | 0.4363 | 1.2426 | 0.081* | 0.70 |
H31C | 0.3501 | 0.3217 | 1.1942 | 0.081* | 0.70 |
C28B | 0.300 (2) | 0.4835 (14) | 1.0220 (10) | 0.090* | 0.30 |
H28C | 0.3490 | 0.4347 | 0.9949 | 0.108* | 0.30 |
H28D | 0.1879 | 0.4450 | 1.0234 | 0.108* | 0.30 |
C29B | 0.376 (2) | 0.5201 (13) | 1.1025 (9) | 0.062 (5)* | 0.30 |
H29C | 0.4893 | 0.5497 | 1.0998 | 0.074* | 0.30 |
H29D | 0.3390 | 0.5795 | 1.1247 | 0.074* | 0.30 |
C30B | 0.334 (2) | 0.4200 (13) | 1.1518 (9) | 0.071 (4)* | 0.30 |
H30C | 0.3348 | 0.3528 | 1.1218 | 0.086* | 0.30 |
H30D | 0.4134 | 0.4333 | 1.1927 | 0.086* | 0.30 |
C31B | 0.177 (3) | 0.400 (3) | 1.1845 (16) | 0.100* | 0.30 |
H31D | 0.1543 | 0.3340 | 1.2134 | 0.150* | 0.30 |
H31E | 0.0983 | 0.3877 | 1.1443 | 0.150* | 0.30 |
H31F | 0.1777 | 0.4640 | 1.2168 | 0.150* | 0.30 |
U11 | U22 | U33 | U12 | U13 | U23 | |
Br1 | 0.0452 (2) | 0.02315 (15) | 0.03853 (18) | 0.00647 (12) | 0.00596 (13) | 0.00699 (11) |
O5 | 0.0275 (10) | 0.0252 (10) | 0.0299 (10) | 0.0006 (8) | −0.0061 (8) | 0.0031 (8) |
O6 | 0.0267 (11) | 0.0348 (12) | 0.0421 (12) | 0.0041 (9) | 0.0009 (9) | 0.0138 (9) |
N2 | 0.0235 (12) | 0.0192 (11) | 0.0251 (11) | 0.0036 (9) | −0.0029 (9) | 0.0043 (9) |
O8 | 0.0500 (14) | 0.0376 (12) | 0.0297 (11) | 0.0037 (10) | −0.0017 (10) | 0.0126 (9) |
O4 | 0.0413 (12) | 0.0334 (11) | 0.0328 (11) | 0.0039 (10) | −0.0123 (9) | 0.0072 (9) |
O10 | 0.0711 (17) | 0.0278 (12) | 0.0394 (13) | −0.0068 (11) | −0.0079 (12) | 0.0053 (10) |
O2 | 0.0437 (12) | 0.0343 (12) | 0.0262 (11) | 0.0063 (10) | −0.0071 (9) | 0.0024 (9) |
N1 | 0.0343 (13) | 0.0214 (12) | 0.0345 (13) | 0.0036 (10) | 0.0003 (11) | 0.0076 (10) |
O9 | 0.0687 (16) | 0.0267 (11) | 0.0385 (13) | 0.0011 (11) | 0.0061 (11) | 0.0095 (9) |
O1 | 0.0562 (15) | 0.0393 (13) | 0.0401 (13) | 0.0007 (11) | −0.0164 (11) | −0.0043 (10) |
C32 | 0.0262 (14) | 0.0264 (14) | 0.0263 (14) | 0.0077 (12) | −0.0006 (11) | 0.0030 (11) |
O7 | 0.0429 (14) | 0.0422 (14) | 0.0581 (15) | −0.0104 (11) | −0.0206 (12) | 0.0251 (11) |
C10 | 0.0277 (14) | 0.0211 (13) | 0.0261 (14) | 0.0013 (11) | −0.0014 (11) | 0.0052 (11) |
C13 | 0.0237 (14) | 0.0246 (14) | 0.0236 (13) | 0.0061 (11) | −0.0013 (11) | 0.0036 (11) |
C4 | 0.0235 (14) | 0.0223 (13) | 0.0260 (14) | 0.0056 (11) | −0.0010 (11) | 0.0029 (11) |
C5 | 0.0246 (14) | 0.0219 (13) | 0.0276 (14) | 0.0075 (11) | −0.0016 (11) | 0.0001 (11) |
C14 | 0.0238 (14) | 0.0185 (13) | 0.0336 (15) | 0.0017 (11) | −0.0001 (11) | 0.0035 (11) |
C6 | 0.0304 (15) | 0.0246 (14) | 0.0299 (15) | 0.0102 (12) | −0.0010 (12) | 0.0027 (11) |
C16 | 0.0279 (15) | 0.0243 (14) | 0.0352 (16) | 0.0092 (12) | 0.0052 (12) | 0.0095 (12) |
C12 | 0.0248 (14) | 0.0252 (14) | 0.0283 (14) | 0.0079 (11) | −0.0007 (11) | 0.0022 (11) |
C11 | 0.0231 (14) | 0.0285 (14) | 0.0291 (15) | 0.0043 (11) | 0.0024 (11) | 0.0044 (11) |
C15 | 0.0285 (15) | 0.0290 (15) | 0.0346 (16) | 0.0073 (13) | 0.0007 (12) | 0.0083 (12) |
C9 | 0.0252 (14) | 0.0200 (13) | 0.0210 (13) | 0.0041 (11) | −0.0066 (10) | 0.0007 (10) |
C33 | 0.0272 (15) | 0.0258 (14) | 0.0356 (16) | 0.0022 (12) | −0.0060 (12) | −0.0013 (12) |
C2 | 0.0287 (15) | 0.0223 (14) | 0.0327 (15) | 0.0069 (12) | 0.0006 (12) | −0.0016 (11) |
C21 | 0.0352 (16) | 0.0246 (14) | 0.0303 (15) | 0.0069 (12) | 0.0029 (12) | 0.0056 (11) |
O3 | 0.0659 (18) | 0.082 (2) | 0.0400 (14) | 0.0141 (16) | −0.0042 (12) | 0.0262 (14) |
C17 | 0.0261 (15) | 0.0301 (15) | 0.0351 (16) | 0.0053 (12) | 0.0011 (12) | 0.0072 (12) |
C34 | 0.0265 (15) | 0.0303 (16) | 0.0421 (18) | 0.0024 (12) | −0.0052 (13) | 0.0029 (13) |
C7 | 0.0472 (19) | 0.0268 (15) | 0.0349 (17) | 0.0071 (14) | −0.0043 (14) | 0.0089 (13) |
C19 | 0.0495 (19) | 0.0229 (14) | 0.0328 (16) | 0.0068 (14) | 0.0066 (14) | 0.0066 (12) |
C25 | 0.0335 (16) | 0.0304 (15) | 0.0329 (16) | 0.0097 (13) | −0.0038 (13) | −0.0024 (13) |
C20 | 0.0442 (18) | 0.0212 (14) | 0.0363 (17) | 0.0048 (13) | 0.0032 (14) | 0.0005 (12) |
C3 | 0.0276 (14) | 0.0246 (14) | 0.0272 (14) | 0.0072 (12) | −0.0023 (11) | −0.0030 (11) |
C8 | 0.0358 (17) | 0.0247 (15) | 0.0508 (19) | 0.0040 (13) | −0.0024 (14) | −0.0016 (14) |
C26 | 0.054 (2) | 0.050 (2) | 0.0262 (16) | 0.0135 (17) | −0.0073 (14) | 0.0052 (14) |
C18 | 0.0379 (17) | 0.0318 (16) | 0.0285 (15) | 0.0115 (13) | 0.0054 (12) | 0.0066 (12) |
C24 | 0.053 (2) | 0.0328 (17) | 0.044 (2) | 0.0022 (16) | −0.0047 (16) | 0.0020 (15) |
C36 | 0.044 (2) | 0.060 (2) | 0.0438 (19) | 0.0244 (18) | 0.0135 (16) | 0.0187 (17) |
C22 | 0.048 (2) | 0.064 (2) | 0.043 (2) | 0.0007 (19) | −0.0078 (16) | 0.0201 (18) |
C23 | 0.081 (3) | 0.043 (2) | 0.049 (2) | −0.009 (2) | 0.023 (2) | 0.0077 (17) |
C35 | 0.040 (2) | 0.044 (2) | 0.061 (2) | −0.0057 (16) | 0.0009 (17) | 0.0230 (17) |
C27 | 0.069 (3) | 0.057 (2) | 0.040 (2) | 0.006 (2) | −0.0143 (18) | 0.0160 (17) |
C37 | 0.070 (3) | 0.095 (4) | 0.067 (3) | 0.025 (3) | 0.020 (2) | 0.043 (3) |
C38 | 0.095 (4) | 0.092 (4) | 0.066 (3) | 0.043 (3) | 0.026 (3) | 0.038 (3) |
C28 | 0.091 (5) | 0.037 (3) | 0.037 (3) | 0.015 (3) | −0.010 (3) | 0.008 (2) |
C29 | 0.079 (5) | 0.059 (4) | 0.042 (3) | 0.010 (4) | −0.009 (3) | 0.020 (3) |
C30 | 0.072 (5) | 0.036 (3) | 0.074 (5) | 0.013 (3) | −0.004 (3) | −0.004 (3) |
C31 | 0.075 (4) | 0.042 (3) | 0.037 (3) | 0.006 (3) | −0.001 (3) | 0.007 (2) |
O5—C32 | 1.367 (3) | C7—H7C | 0.9600 |
O5—C33 | 1.441 (3) | C19—C20 | 1.388 (4) |
O6—C35 | 1.422 (4) | C19—C18 | 1.396 (4) |
O6—C34 | 1.424 (4) | C25—C3 | 1.463 (4) |
N2—C13 | 1.347 (3) | C8—H8A | 0.9600 |
N2—C12 | 1.349 (3) | C8—H8B | 0.9600 |
N2—C14 | 1.470 (3) | C8—H8C | 0.9600 |
O8—C18 | 1.358 (4) | C26—C27 | 1.479 (5) |
O8—C22 | 1.417 (4) | C26—H26A | 0.9700 |
O4—C32 | 1.212 (3) | C26—H26B | 0.9700 |
O10—C20 | 1.365 (4) | C24—H24A | 0.9600 |
O10—C24 | 1.424 (4) | C24—H24B | 0.9600 |
O2—C25 | 1.353 (4) | C24—H24C | 0.9600 |
O2—C26 | 1.440 (4) | C36—C35 | 1.473 (5) |
N1—C2 | 1.375 (4) | C36—C37 | 1.534 (5) |
N1—C6 | 1.376 (4) | C36—H36A | 0.9700 |
N1—H1 | 0.8600 | C36—H36B | 0.9700 |
O9—C19 | 1.373 (4) | C22—H22A | 0.9600 |
O9—C23 | 1.435 (5) | C22—H22B | 0.9600 |
O1—C25 | 1.215 (4) | C22—H22C | 0.9600 |
C32—C5 | 1.460 (4) | C23—H23A | 0.9600 |
O7—C15 | 1.211 (4) | C23—H23B | 0.9600 |
C10—C9 | 1.384 (4) | C23—H23C | 0.9600 |
C10—C11 | 1.386 (4) | C35—H32A | 0.9700 |
C10—H10 | 0.9300 | C35—H32B | 0.9700 |
C13—C9 | 1.385 (4) | C27—H27A | 0.9700 |
C13—H13 | 0.9300 | C27—H27B | 0.9700 |
C4—C3 | 1.520 (4) | C37—C38 | 1.452 (6) |
C4—C5 | 1.528 (4) | C37—H37A | 0.9700 |
C4—C9 | 1.537 (4) | C37—H37B | 0.9700 |
C4—H4 | 0.9800 | C38—H38A | 0.9600 |
C5—C6 | 1.356 (4) | C38—H38B | 0.9600 |
C14—C15 | 1.518 (4) | C38—H38C | 0.9600 |
C14—H14A | 0.9700 | C28—C29 | 1.490 (8) |
C14—H14B | 0.9700 | C28—H28A | 0.9700 |
C6—C7 | 1.498 (4) | C28—H28B | 0.9700 |
C16—C17 | 1.391 (4) | C29—C30 | 1.510 (9) |
C16—C21 | 1.399 (4) | C29—H29A | 0.9700 |
C16—C15 | 1.485 (4) | C29—H29B | 0.9700 |
C12—C11 | 1.375 (4) | C30—C31 | 1.501 (9) |
C12—H12 | 0.9300 | C30—H30A | 0.9700 |
C11—H11 | 0.9300 | C30—H30B | 0.9700 |
C33—C34 | 1.489 (4) | C31—H31A | 0.9600 |
C33—H33A | 0.9700 | C31—H31B | 0.9600 |
C33—H33B | 0.9700 | C31—H31C | 0.9600 |
C2—C3 | 1.349 (4) | C28B—C29B | 1.544 (17) |
C2—C8 | 1.501 (4) | C28B—H28C | 0.9700 |
C21—C20 | 1.387 (4) | C28B—H28D | 0.9700 |
C21—H21 | 0.9300 | C29B—C30B | 1.520 (16) |
O3—C28B | 1.404 (15) | C29B—H29C | 0.9700 |
O3—C27 | 1.417 (4) | C29B—H29D | 0.9700 |
O3—C28 | 1.427 (6) | C30B—C31B | 1.486 (17) |
C17—C18 | 1.390 (4) | C30B—H30C | 0.9700 |
C17—H17 | 0.9300 | C30B—H30D | 0.9700 |
C34—H34A | 0.9700 | C31B—H31D | 0.9600 |
C34—H34B | 0.9700 | C31B—H31E | 0.9600 |
C7—H7A | 0.9600 | C31B—H31F | 0.9600 |
C7—H7B | 0.9600 | ||
C32—O5—C33 | 116.7 (2) | C27—C26—H26A | 110.1 |
C35—O6—C34 | 111.0 (2) | O2—C26—H26B | 110.1 |
C13—N2—C12 | 121.7 (2) | C27—C26—H26B | 110.1 |
C13—N2—C14 | 119.6 (2) | H26A—C26—H26B | 108.4 |
C12—N2—C14 | 118.7 (2) | O8—C18—C17 | 124.9 (3) |
C18—O8—C22 | 117.6 (3) | O8—C18—C19 | 115.4 (3) |
C20—O10—C24 | 118.0 (3) | C17—C18—C19 | 119.8 (3) |
C25—O2—C26 | 114.4 (2) | O10—C24—H24A | 109.5 |
C2—N1—C6 | 124.0 (2) | O10—C24—H24B | 109.5 |
C2—N1—H1 | 118.0 | H24A—C24—H24B | 109.5 |
C6—N1—H1 | 118.0 | O10—C24—H24C | 109.5 |
C19—O9—C23 | 111.4 (3) | H24A—C24—H24C | 109.5 |
O4—C32—O5 | 121.2 (2) | H24B—C24—H24C | 109.5 |
O4—C32—C5 | 128.1 (3) | C35—C36—C37 | 111.8 (3) |
O5—C32—C5 | 110.7 (2) | C35—C36—H36A | 109.3 |
C9—C10—C11 | 120.0 (3) | C37—C36—H36A | 109.3 |
C9—C10—H10 | 120.0 | C35—C36—H36B | 109.3 |
C11—C10—H10 | 120.0 | C37—C36—H36B | 109.3 |
N2—C13—C9 | 120.7 (2) | H36A—C36—H36B | 107.9 |
N2—C13—H13 | 119.7 | O8—C22—H22A | 109.5 |
C9—C13—H13 | 119.7 | O8—C22—H22B | 109.5 |
C3—C4—C5 | 111.6 (2) | H22A—C22—H22B | 109.5 |
C3—C4—C9 | 110.2 (2) | O8—C22—H22C | 109.5 |
C5—C4—C9 | 108.0 (2) | H22A—C22—H22C | 109.5 |
C3—C4—H4 | 109.0 | H22B—C22—H22C | 109.5 |
C5—C4—H4 | 109.0 | O9—C23—H23A | 109.5 |
C9—C4—H4 | 109.0 | O9—C23—H23B | 109.5 |
C6—C5—C32 | 120.9 (2) | H23A—C23—H23B | 109.5 |
C6—C5—C4 | 120.8 (2) | O9—C23—H23C | 109.5 |
C32—C5—C4 | 118.0 (2) | H23A—C23—H23C | 109.5 |
N2—C14—C15 | 110.2 (2) | H23B—C23—H23C | 109.5 |
N2—C14—H14A | 109.6 | O6—C35—C36 | 112.1 (3) |
C15—C14—H14A | 109.6 | O6—C35—H32A | 109.2 |
N2—C14—H14B | 109.6 | C36—C35—H32A | 109.2 |
C15—C14—H14B | 109.6 | O6—C35—H32B | 109.2 |
H14A—C14—H14B | 108.1 | C36—C35—H32B | 109.2 |
C5—C6—N1 | 119.6 (3) | H32A—C35—H32B | 107.9 |
C5—C6—C7 | 126.7 (3) | O3—C27—C26 | 105.7 (3) |
N1—C6—C7 | 113.7 (2) | O3—C27—H27A | 110.6 |
C17—C16—C21 | 121.1 (3) | C26—C27—H27A | 110.6 |
C17—C16—C15 | 117.7 (3) | O3—C27—H27B | 110.6 |
C21—C16—C15 | 121.2 (3) | C26—C27—H27B | 110.6 |
N2—C12—C11 | 119.4 (2) | H27A—C27—H27B | 108.7 |
N2—C12—H12 | 120.3 | C38—C37—C36 | 115.5 (4) |
C11—C12—H12 | 120.3 | C38—C37—H37A | 108.4 |
C12—C11—C10 | 119.9 (3) | C36—C37—H37A | 108.4 |
C12—C11—H11 | 120.1 | C38—C37—H37B | 108.4 |
C10—C11—H11 | 120.1 | C36—C37—H37B | 108.4 |
O7—C15—C16 | 122.1 (3) | H37A—C37—H37B | 107.5 |
O7—C15—C14 | 120.1 (3) | C37—C38—H38A | 109.5 |
C16—C15—C14 | 117.7 (2) | C37—C38—H38B | 109.5 |
C10—C9—C13 | 118.3 (2) | H38A—C38—H38B | 109.5 |
C10—C9—C4 | 121.3 (2) | C37—C38—H38C | 109.5 |
C13—C9—C4 | 120.4 (2) | H38A—C38—H38C | 109.5 |
O5—C33—C34 | 108.9 (2) | H38B—C38—H38C | 109.5 |
O5—C33—H33A | 109.9 | O3—C28—C29 | 113.3 (5) |
C34—C33—H33A | 109.9 | O3—C28—H28A | 108.9 |
O5—C33—H33B | 109.9 | C29—C28—H28A | 108.9 |
C34—C33—H33B | 109.9 | O3—C28—H28B | 108.9 |
H33A—C33—H33B | 108.3 | C29—C28—H28B | 108.9 |
C3—C2—N1 | 120.0 (2) | H28A—C28—H28B | 107.7 |
C3—C2—C8 | 126.3 (3) | C28—C29—C30 | 115.8 (6) |
N1—C2—C8 | 113.7 (3) | C28—C29—H29A | 108.3 |
C20—C21—C16 | 118.9 (3) | C30—C29—H29A | 108.3 |
C20—C21—H21 | 120.5 | C28—C29—H29B | 108.3 |
C16—C21—H21 | 120.5 | C30—C29—H29B | 108.3 |
C28B—O3—C27 | 119.8 (8) | H29A—C29—H29B | 107.4 |
C28B—O3—C28 | 30.1 (8) | C31—C30—C29 | 112.9 (6) |
C27—O3—C28 | 113.2 (3) | C31—C30—H30A | 109.0 |
C18—C17—C16 | 119.4 (3) | C29—C30—H30A | 109.0 |
C18—C17—H17 | 120.3 | C31—C30—H30B | 109.0 |
C16—C17—H17 | 120.3 | C29—C30—H30B | 109.0 |
O6—C34—C33 | 110.7 (2) | H30A—C30—H30B | 107.8 |
O6—C34—H34A | 109.5 | C30—C31—H31A | 109.5 |
C33—C34—H34A | 109.5 | C30—C31—H31B | 109.5 |
O6—C34—H34B | 109.5 | H31A—C31—H31B | 109.5 |
C33—C34—H34B | 109.5 | C30—C31—H31C | 109.5 |
H34A—C34—H34B | 108.1 | H31A—C31—H31C | 109.5 |
C6—C7—H7A | 109.5 | H31B—C31—H31C | 109.5 |
C6—C7—H7B | 109.5 | O3—C28B—C29B | 101.9 (12) |
H7A—C7—H7B | 109.5 | O3—C28B—H28C | 111.4 |
C6—C7—H7C | 109.5 | C29B—C28B—H28C | 111.4 |
H7A—C7—H7C | 109.5 | O3—C28B—H28D | 111.4 |
H7B—C7—H7C | 109.5 | C29B—C28B—H28D | 111.4 |
O9—C19—C20 | 120.4 (3) | H28C—C28B—H28D | 109.3 |
O9—C19—C18 | 119.3 (3) | C30B—C29B—C28B | 110.1 (13) |
C20—C19—C18 | 120.3 (3) | C30B—C29B—H29C | 109.6 |
O1—C25—O2 | 120.9 (3) | C28B—C29B—H29C | 109.6 |
O1—C25—C3 | 127.7 (3) | C30B—C29B—H29D | 109.6 |
O2—C25—C3 | 111.4 (2) | C28B—C29B—H29D | 109.6 |
O10—C20—C21 | 124.7 (3) | H29C—C29B—H29D | 108.2 |
O10—C20—C19 | 114.8 (3) | C31B—C30B—C29B | 112.6 (17) |
C21—C20—C19 | 120.5 (3) | C31B—C30B—H30C | 109.1 |
C2—C3—C25 | 121.1 (3) | C29B—C30B—H30C | 109.1 |
C2—C3—C4 | 121.0 (2) | C31B—C30B—H30D | 109.1 |
C25—C3—C4 | 117.8 (2) | C29B—C30B—H30D | 109.1 |
C2—C8—H8A | 109.5 | H30C—C30B—H30D | 107.8 |
C2—C8—H8B | 109.5 | C30B—C31B—H31D | 109.5 |
H8A—C8—H8B | 109.5 | C30B—C31B—H31E | 109.5 |
C2—C8—H8C | 109.5 | H31D—C31B—H31E | 109.5 |
H8A—C8—H8C | 109.5 | C30B—C31B—H31F | 109.5 |
H8B—C8—H8C | 109.5 | H31D—C31B—H31F | 109.5 |
O2—C26—C27 | 107.9 (3) | H31E—C31B—H31F | 109.5 |
O2—C26—H26A | 110.1 |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···Br1i | 0.86 | 2.61 | 3.421 (2) | 157 |
Symmetry code: (i) x, y+1, z. |
Experimental details
Crystal data | |
Chemical formula | C37H51N2O10+·Br− |
Mr | 763.71 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 190 |
a, b, c (Å) | 8.9501 (2), 12.4741 (3), 17.6994 (5) |
α, β, γ (°) | 93.057 (1), 91.658 (1), 108.024 (1) |
V (Å3) | 1874.25 (8) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 1.16 |
Crystal size (mm) | 0.32 × 0.18 × 0.16 |
Data collection | |
Diffractometer | Nonius KappaCCD |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 13618, 8822, 6509 |
Rint | 0.035 |
(sin θ/λ)max (Å−1) | 0.657 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.056, 0.127, 1.03 |
No. of reflections | 8822 |
No. of parameters | 469 |
No. of restraints | 4 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 1.15, −0.41 |
Computer programs: COLLECT (Hooft, 1998), DENZO and SCALEPACK (Otwinowski & Minor, 1997), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 (Farrugia, 2012).
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···Br1i | 0.86 | 2.61 | 3.421 (2) | 157 |
Symmetry code: (i) x, y+1, z. |
Acknowledgements
The study was supported by the Latvian National Research programme 2010–2013 `Development of prevention, treatment, diagnostic means and practices, and biomedicine technologies for improvement of public health'.
References
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Nowadays considerable attention is paid to the synthesis of 1,4-dihydropyridine (1,4-DHP) derivatives because of their wide spectrum of biological activity. Slight variations in 1,4-DHP ring substituents can result in considerable changes in pharmacological effects (Swarnalatha et al., 2011). 1,4-Dihydropyridines are considered as privileged structures, because these compounds are capable to bind to multiple receptors with high affinity (Ruiz et al., 2012).
It was found that the concentration of adenosine, the natural ligand of the A2A receptor, changes in the ischemia, hypoxia and inflammation conditions (Hasko & Pacher, 2008). The A2A receptor is believed to play a role in cardioprotection, inflammation, stroke and certain central nervous system disorders (Niebauer & Robinson, 2006). We were looking for molecules based on 1,4-DHP able to bind A2A adenosine receptors and possessing enhanced water solubility.
Fig. 1 shows a view of the crystal structure of the title compound. For the disordered butoxy fragment only atoms with the higher occupation factor are shown. In the crystal structure, the 1,4-DHP ring adopts a slightly puckered boat conformation. Atoms N1 and C4 deviate from the least-squares plane calculated through the four other ring atoms by 0.068 (5) Å and 0.224 (5) Å, respectively. The orientation of both C=O groups is cis with respect to the double bonds of 1,4-DHP. The pyridinium ring has an axial orientation with respect to the 1,4-DHP ring and is almost perpendicular to the least-squares average plane of the 1,4-DHP ring with a dihedral angle between both planes of 89.2 (3)°. The molecule has a compact shape with all long chain substituents oriented approximately in one direction. All bonds in the substituents at the 3 and 5 position of 1,4-DHP have trans orientation except for bonds C29B—C30B and C33—C34 (gauche-). The bromine anion forms a weak hydrogen bond with N1—H1 of a neighboring 1,4-DHP ring. The distance between the bromine ion and the positively charged N2 atom is 4.185 (5) Å.