Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807037890/pv2022sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807037890/pv2022Isup2.hkl |
CCDC reference: 660236
Key indicators
- Single-crystal X-ray study
- T = 293 K
- Mean (C-C) = 0.004 Å
- R factor = 0.058
- wR factor = 0.121
- Data-to-parameter ratio = 11.7
checkCIF/PLATON results
No syntax errors found
Alert level B PLAT220_ALERT_2_B Large Non-Solvent C Ueq(max)/Ueq(min) ... 3.54 Ratio PLAT222_ALERT_3_B Large Non-Solvent H Ueq(max)/Ueq(min) ... 4.93 Ratio PLAT735_ALERT_1_B D-H Calc 0.93(3), Rep 0.929(4) ...... 7.50 su-Ra C17 -H17B 1.555 1.555 PLAT735_ALERT_1_B D-H Calc 0.91(4), Rep 0.911(5) ...... 8.00 su-Ra C15 -H15B 1.555 1.555 PLAT735_ALERT_1_B D-H Calc 0.89(3), Rep 0.892(6) ...... 5.00 su-Ra N1 -H1N 1.555 1.555 PLAT735_ALERT_1_B D-H Calc 0.98(3), Rep 0.979(6) ...... 5.00 su-Ra C4 -H4 1.555 1.555 PLAT736_ALERT_1_B H...A Calc 2.52(3), Rep 2.515(4) ...... 7.50 su-Ra H17B -O3 1.555 3.665 PLAT736_ALERT_1_B H...A Calc 2.79(4), Rep 2.794(7) ...... 5.71 su-Ra H15B -O4 1.555 3.565 PLAT736_ALERT_1_B H...A Calc 2.02(3), Rep 2.024(6) ...... 5.00 su-Ra H1N -O4 1.555 3.565
Alert level C ABSTY03_ALERT_1_C The _exptl_absorpt_correction_type has been given as none. However values have been given for Tmin and Tmax. Remove these if an absorption correction has not been applied. From the CIF: _exptl_absorpt_correction_T_min 1.000 From the CIF: _exptl_absorpt_correction_T_max 1.000 PLAT125_ALERT_4_C No _symmetry_space_group_name_Hall Given ....... ? PLAT242_ALERT_2_C Check Low Ueq as Compared to Neighbors for C12 PLAT391_ALERT_3_C Deviating Methyl C15 H-C-H Bond Angle ...... 101.00 Deg. PLAT480_ALERT_4_C Long H...A H-Bond Reported H15B .. O4 .. 2.79 Ang. PLAT736_ALERT_1_C H...A Calc 2.58(2), Rep 2.572(6) ...... 3.33 su-Ra H4 -O1 1.555 4.576 PLAT790_ALERT_4_C Centre of Gravity not Within Unit Cell: Resd. # 1 C17 H20 N2 O5
Alert level G PLAT199_ALERT_1_G Check the Reported _cell_measurement_temperature 293 K PLAT200_ALERT_1_G Check the Reported _diffrn_ambient_temperature . 293 K PLAT793_ALERT_1_G Check the Absolute Configuration of C7 = ... R
0 ALERT level A = In general: serious problem 9 ALERT level B = Potentially serious problem 7 ALERT level C = Check and explain 3 ALERT level G = General alerts; check 12 ALERT type 1 CIF construction/syntax error, inconsistent or missing data 2 ALERT type 2 Indicator that the structure model may be wrong or deficient 2 ALERT type 3 Indicator that the structure quality may be low 3 ALERT type 4 Improvement, methodology, query or suggestion 0 ALERT type 5 Informative message, check
5-Ethoxycarbonyl-6-methyl-4-(4-methoxyphynyl)- 3,4-dihydropyrimidine-2(1H)-one was prepared by refluxing a mixture of ethyl acetoacetate solution (3.12 g, 24 mM), acetaldehyde (2.72 g, 20 mM) and lithium bromide (0.175 g, 2 mM) in acetonitrile (25 ml) for 5 h, in a 100 ml round bottom flask. After cooling, the reaction mixture was poured in to crushed ice and stirred for several minutes. The solid product was filtered, washed with cold water, dried and recrystallized from ethanol (yield = 5.17 g, 89.1% and the melting point = 474 K). To prepare the acetyl derivative (title compound), 2 g of this product was mixed with 10 ml of acetic anhydride and refluxed for 4 h in a 25 ml round bottom flask. The reaction mixture was cooled and diluted by adding 20 ml of water·The acetyl derivative seperated out as an oil. The mixture was vigorously stirred and was allowed to solidify. It was filtered, washed thoroughly with water and crystallized from an acetone-water mixture. The yield was 1.94 g (85.0%) and the melting point was 413 K. X-ray diffraction quality single crystals were grown from a solution of chloroform by slow evaporation.
All H atoms were located from Fourier difference maps and refined with isotropic thermal displacement parameters; the H-atoms bonded to C13 were included in the refinement at geometrically idealized positions with C—H = 0.96 A° and Uiso = 1.5xUeq C13.
4-Aryldihydropyrimidines (DHPMs) represent a heterocyclic system of remarkable pharmacological efficiency. They have recently emerged as important target molecules due to their therapeutic and medicinal properties (Kappe, 2000) such as antiviral (Hurst et al., 1961), antimitotic (Mayer et al., 1999), and antihypertensive (Atwal et al., 1991). They are also the most studied class of organic calcium channel modulators (Kappe, 1998; Jauk et al., 2000) and since their introduction into clinical medicine in 1975, they have become almost indispensable for the treatment of cardiovascular diseases such as hypertension, cardiac arrhythmias, or angina (Janis et al., 1987). These inherently asymmetric compounds have been studied extensively to expand the existing structure-activity relationships and to get further insight into molecular interactions at the receptor-site level (Cho et al., 1989; Atwal et al., 1990; Rovnyak et al., 1992 and Grover et al., 1995).
The title compound (I) is a calcium antagonist and belongs to dihydropyrimidine heterocycles. In this molecule (Fig. 1) the substituted aryl ring is positioned axially, perpendicular to, and nearly bisects the boat-like dihydropyrimidine ring. This is evident as the dihedral angle between the planes of both ring systems is 84.92 (7)°. The 4-aryl substitutent (methoxy group) adopts a synperiplanar position. These features have been found mandatory for optimum calcium channel modulatory activity according to the recently proposed new binding-site model for this class of cardiovascular drugs (Rovnyak et al., 1995; Triggle et al., 1995). The exocyclic ester at C8 adopts a trans orientation with respect to C8—C9 double bond. DHPM's of this type are known to show conformational flexibility, where, the aryl ring and the ester group can rotate and the conformation of dihydropyrimidine ring can change (Kappe et al., 1997; Shishkin et al., 1997). The crystal structure is stabilized by intermolecular C—H···O and N—H···O hydrogen bonds (Fig. 2).
For related literature, see: Atwal et al. (1990, 1991); Cho et al. (1989); Grover et al. (1995); Hurst & Hull (1961); Janis et al. (1987); Jauk et al. (2000); Kappe (1998, 2000); Kappe et al. (1997); Mayer et al. (1999); Rovnyak et al. (1992, 1995); Shishkin et al. (1997); Triggle & Padmanabhan (1995).
Data collection: SMART (Bruker, 1998); cell refinement: SMART; data reduction: SAINT (Bruker, 1998); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).
Fig. 1. The molecular structure of (I), showing 50% probability displacement ellipsoids. | |
Fig. 2. A view of the unit cell showing intermolecular C—H···O and N—H···O hydrogen bonding interactions. |
C17H20N2O5 | F(000) = 704 |
Mr = 332.35 | Dx = 1.296 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
a = 8.8387 (8) Å | Cell parameters from 500 reflections |
b = 20.2043 (18) Å | θ = 1.0–25.0° |
c = 10.0232 (9) Å | µ = 0.10 mm−1 |
β = 107.839 (2)° | T = 293 K |
V = 1703.9 (3) Å3 | Rectangular, colourless |
Z = 4 | 0.3 × 0.2 × 0.1 mm |
Bruker SMART CCD area-detector diffractometer | 2369 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.045 |
Graphite monochromator | θmax = 26.0°, θmin = 2.0° |
ω/2θ scans | h = −10→10 |
17507 measured reflections | k = −24→24 |
3343 independent reflections | l = −12→12 |
Refinement on F2 | 0 restraints |
Least-squares matrix: full | H atoms treated by a mixture of independent and constrained refinement |
R[F2 > 2σ(F2)] = 0.058 | w = 1/[σ2(Fo2) + (0.0393P)2 + 0.4822P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.121 | (Δ/σ)max < 0.001 |
S = 1.10 | Δρmax = 0.20 e Å−3 |
3343 reflections | Δρmin = −0.17 e Å−3 |
286 parameters |
C17H20N2O5 | V = 1703.9 (3) Å3 |
Mr = 332.35 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 8.8387 (8) Å | µ = 0.10 mm−1 |
b = 20.2043 (18) Å | T = 293 K |
c = 10.0232 (9) Å | 0.3 × 0.2 × 0.1 mm |
β = 107.839 (2)° |
Bruker SMART CCD area-detector diffractometer | 2369 reflections with I > 2σ(I) |
17507 measured reflections | Rint = 0.045 |
3343 independent reflections |
R[F2 > 2σ(F2)] = 0.058 | 0 restraints |
wR(F2) = 0.121 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.10 | Δρmax = 0.20 e Å−3 |
3343 reflections | Δρmin = −0.17 e Å−3 |
286 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. |
x | y | z | Uiso*/Ueq | ||
C1 | 0.1807 (3) | 0.62671 (14) | −0.4147 (3) | 0.0578 (7) | |
H1 | 0.258 (3) | 0.5977 (12) | −0.434 (2) | 0.064 (7)* | |
C2 | 0.0648 (3) | 0.65191 (14) | −0.5284 (3) | 0.0610 (7) | |
H2 | 0.062 (3) | 0.6393 (12) | −0.620 (3) | 0.067 (8)* | |
C3 | −0.0503 (3) | 0.69434 (11) | −0.5095 (2) | 0.0467 (6) | |
C4 | −0.0447 (3) | 0.71195 (11) | −0.3757 (3) | 0.0468 (6) | |
H4 | −0.122 (3) | 0.7428 (12) | −0.358 (2) | 0.063 (7)* | |
C5 | 0.0738 (3) | 0.68632 (11) | −0.2623 (3) | 0.0440 (6) | |
H5 | 0.070 (2) | 0.6976 (10) | −0.169 (2) | 0.046 (6)* | |
C6 | 0.1872 (2) | 0.64294 (10) | −0.2785 (2) | 0.0392 (5) | |
C7 | 0.3185 (3) | 0.61621 (11) | −0.1535 (2) | 0.0397 (5) | |
H7 | 0.409 (2) | 0.6440 (10) | −0.140 (2) | 0.041 (6)* | |
C8 | 0.3650 (2) | 0.54550 (10) | −0.1719 (2) | 0.0381 (5) | |
C9 | 0.2724 (2) | 0.49805 (11) | −0.1439 (2) | 0.0399 (5) | |
C10 | 0.1584 (3) | 0.57494 (10) | −0.0123 (2) | 0.0407 (5) | |
C11 | −0.2841 (4) | 0.75841 (19) | −0.6132 (4) | 0.0755 (9) | |
H11A | −0.228 (4) | 0.8003 (16) | −0.564 (3) | 0.097 (11)* | |
H11B | −0.348 (4) | 0.7666 (15) | −0.709 (3) | 0.089 (10)* | |
H11C | −0.340 (4) | 0.7379 (17) | −0.553 (4) | 0.113 (13)* | |
C12 | 0.7234 (4) | 0.5743 (2) | −0.2778 (4) | 0.0732 (9) | |
H12A | 0.787 (4) | 0.6143 (18) | −0.245 (3) | 0.110 (12)* | |
H12B | 0.785 (5) | 0.533 (2) | −0.233 (4) | 0.135 (15)* | |
C13 | 0.6866 (5) | 0.5672 (2) | −0.4278 (4) | 0.1348 (18) | |
H13A | 0.6245 | 0.5278 | −0.4578 | 0.202* | |
H13B | 0.7835 | 0.564 | −0.4518 | 0.202* | |
H13C | 0.6272 | 0.605 | −0.4735 | 0.202* | |
C14 | 0.5045 (3) | 0.52967 (12) | −0.2155 (2) | 0.0438 (5) | |
C15 | 0.2798 (4) | 0.42479 (13) | −0.1633 (4) | 0.0560 (7) | |
H15A | 0.297 (4) | 0.4137 (17) | −0.246 (4) | 0.113 (13)* | |
H15B | 0.189 (4) | 0.4038 (15) | −0.162 (3) | 0.094 (11)* | |
H15C | 0.353 (5) | 0.4051 (18) | −0.088 (4) | 0.130 (15)* | |
C16 | 0.3369 (3) | 0.67056 (11) | 0.0735 (2) | 0.0471 (6) | |
C17 | 0.3006 (4) | 0.67190 (17) | 0.2084 (3) | 0.0591 (7) | |
H17A | 0.191 (4) | 0.6850 (15) | 0.193 (3) | 0.098 (11)* | |
H17B | 0.308 (4) | 0.6307 (17) | 0.251 (3) | 0.094 (11)* | |
H17C | 0.361 (3) | 0.7043 (15) | 0.268 (3) | 0.084 (10)* | |
O1 | −0.1630 (2) | 0.71530 (9) | −0.62888 (17) | 0.0611 (5) | |
O2 | 0.57984 (19) | 0.58430 (8) | −0.2372 (2) | 0.0627 (5) | |
O3 | 0.5508 (2) | 0.47512 (9) | −0.2308 (2) | 0.0711 (6) | |
O4 | 0.06853 (18) | 0.58291 (8) | 0.05764 (17) | 0.0536 (4) | |
O5 | 0.4247 (2) | 0.71030 (9) | 0.04514 (19) | 0.0704 (6) | |
N1 | 0.1531 (2) | 0.51820 (9) | −0.0891 (2) | 0.0438 (5) | |
H1N | 0.089 (3) | 0.4869 (12) | −0.074 (2) | 0.059 (7)* | |
N2 | 0.2716 (2) | 0.62013 (8) | −0.02432 (18) | 0.0388 (4) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0586 (16) | 0.0689 (18) | 0.0530 (16) | 0.0169 (14) | 0.0274 (14) | 0.0014 (13) |
C2 | 0.0663 (17) | 0.080 (2) | 0.0411 (15) | 0.0147 (15) | 0.0236 (14) | 0.0033 (14) |
C3 | 0.0484 (14) | 0.0458 (13) | 0.0492 (14) | 0.0001 (11) | 0.0200 (12) | 0.0091 (11) |
C4 | 0.0495 (14) | 0.0383 (13) | 0.0563 (16) | 0.0046 (11) | 0.0218 (13) | 0.0014 (11) |
C5 | 0.0484 (14) | 0.0408 (13) | 0.0459 (14) | 0.0027 (11) | 0.0190 (12) | −0.0020 (11) |
C6 | 0.0405 (12) | 0.0353 (12) | 0.0453 (13) | −0.0049 (10) | 0.0182 (10) | 0.0023 (10) |
C7 | 0.0378 (12) | 0.0381 (12) | 0.0475 (14) | −0.0060 (10) | 0.0195 (11) | −0.0030 (10) |
C8 | 0.0357 (12) | 0.0391 (12) | 0.0406 (12) | 0.0013 (9) | 0.0134 (10) | −0.0006 (10) |
C9 | 0.0364 (12) | 0.0409 (12) | 0.0417 (13) | −0.0002 (10) | 0.0108 (10) | −0.0016 (10) |
C10 | 0.0385 (12) | 0.0392 (13) | 0.0461 (13) | 0.0007 (10) | 0.0155 (11) | 0.0017 (10) |
C11 | 0.066 (2) | 0.081 (2) | 0.074 (2) | 0.0226 (18) | 0.0129 (19) | 0.016 (2) |
C12 | 0.0596 (18) | 0.082 (2) | 0.095 (2) | −0.0158 (18) | 0.0481 (18) | −0.017 (2) |
C13 | 0.137 (4) | 0.194 (5) | 0.097 (3) | −0.079 (3) | 0.070 (3) | −0.032 (3) |
C14 | 0.0412 (13) | 0.0463 (14) | 0.0452 (14) | 0.0026 (11) | 0.0150 (11) | 0.0006 (11) |
C15 | 0.0632 (18) | 0.0417 (15) | 0.069 (2) | −0.0047 (14) | 0.0292 (17) | −0.0047 (14) |
C16 | 0.0428 (13) | 0.0403 (13) | 0.0579 (15) | 0.0024 (11) | 0.0152 (12) | −0.0052 (11) |
C17 | 0.068 (2) | 0.0549 (18) | 0.0590 (18) | −0.0015 (15) | 0.0254 (16) | −0.0141 (15) |
O1 | 0.0598 (11) | 0.0713 (12) | 0.0508 (10) | 0.0136 (9) | 0.0147 (9) | 0.0134 (9) |
O2 | 0.0525 (10) | 0.0545 (10) | 0.0973 (14) | −0.0090 (8) | 0.0468 (10) | −0.0080 (10) |
O3 | 0.0733 (13) | 0.0509 (11) | 0.1076 (16) | 0.0149 (9) | 0.0551 (12) | 0.0059 (10) |
O4 | 0.0513 (10) | 0.0548 (10) | 0.0666 (11) | −0.0061 (8) | 0.0357 (9) | −0.0072 (8) |
O5 | 0.0779 (13) | 0.0593 (11) | 0.0818 (13) | −0.0300 (10) | 0.0360 (11) | −0.0210 (10) |
N1 | 0.0406 (11) | 0.0401 (11) | 0.0563 (12) | −0.0084 (9) | 0.0231 (10) | −0.0038 (9) |
N2 | 0.0385 (10) | 0.0369 (10) | 0.0445 (11) | −0.0051 (8) | 0.0178 (8) | −0.0042 (8) |
C1—C2 | 1.375 (4) | C11—H11A | 1.02 (3) |
C1—C6 | 1.387 (3) | C11—H11B | 0.97 (3) |
C1—H1 | 0.96 (2) | C11—H11C | 0.98 (4) |
C2—C3 | 1.387 (3) | C12—C13 | 1.444 (5) |
C2—H2 | 0.95 (3) | C12—O2 | 1.460 (3) |
C3—O1 | 1.369 (3) | C12—H12A | 0.98 (4) |
C3—C4 | 1.374 (3) | C12—H12B | 1.02 (4) |
C4—C5 | 1.389 (3) | C13—H13A | 0.96 |
C4—H4 | 0.98 (2) | C13—H13B | 0.96 |
C5—C6 | 1.378 (3) | C13—H13C | 0.96 |
C5—H5 | 0.97 (2) | C14—O3 | 1.201 (3) |
C6—C7 | 1.523 (3) | C14—O2 | 1.341 (3) |
C7—N2 | 1.478 (3) | C15—H15A | 0.91 (4) |
C7—C8 | 1.513 (3) | C15—H15B | 0.91 (3) |
C7—H7 | 0.95 (2) | C15—H15C | 0.92 (4) |
C8—C9 | 1.345 (3) | C16—O5 | 1.210 (3) |
C8—C14 | 1.464 (3) | C16—N2 | 1.409 (3) |
C9—N1 | 1.391 (3) | C16—C17 | 1.483 (4) |
C9—C15 | 1.497 (3) | C17—H17A | 0.97 (3) |
C10—O4 | 1.221 (2) | C17—H17B | 0.93 (3) |
C10—N1 | 1.373 (3) | C17—H17C | 0.94 (3) |
C10—N2 | 1.387 (3) | N1—H1N | 0.89 (3) |
C11—O1 | 1.426 (3) | ||
C2—C1—C6 | 121.6 (2) | C13—C12—O2 | 111.5 (3) |
C2—C1—H1 | 117.0 (14) | C13—C12—H12A | 110.8 (19) |
C6—C1—H1 | 121.4 (15) | O2—C12—H12A | 104.3 (19) |
C1—C2—C3 | 120.5 (2) | C13—C12—H12B | 107 (2) |
C1—C2—H2 | 119.7 (15) | O2—C12—H12B | 113 (2) |
C3—C2—H2 | 119.8 (15) | H12A—C12—H12B | 111 (3) |
O1—C3—C4 | 124.9 (2) | C12—C13—H13A | 109.5 |
O1—C3—C2 | 116.1 (2) | C12—C13—H13B | 109.5 |
C4—C3—C2 | 119.0 (2) | H13A—C13—H13B | 109.5 |
C3—C4—C5 | 119.7 (2) | C12—C13—H13C | 109.5 |
C3—C4—H4 | 121.8 (14) | H13A—C13—H13C | 109.5 |
C5—C4—H4 | 118.5 (14) | H13B—C13—H13C | 109.5 |
C6—C5—C4 | 122.3 (2) | O3—C14—O2 | 121.9 (2) |
C6—C5—H5 | 120.1 (13) | O3—C14—C8 | 126.1 (2) |
C4—C5—H5 | 117.5 (13) | O2—C14—C8 | 111.97 (19) |
C5—C6—C1 | 117.0 (2) | C9—C15—H15A | 113 (2) |
C5—C6—C7 | 121.8 (2) | C9—C15—H15B | 112.7 (19) |
C1—C6—C7 | 121.2 (2) | H15A—C15—H15B | 107 (3) |
N2—C7—C8 | 108.50 (17) | C9—C15—H15C | 112 (2) |
N2—C7—C6 | 110.76 (17) | H15A—C15—H15C | 111 (3) |
C8—C7—C6 | 113.64 (18) | H15B—C15—H15C | 101 (3) |
N2—C7—H7 | 107.0 (12) | O5—C16—N2 | 118.2 (2) |
C8—C7—H7 | 109.2 (12) | O5—C16—C17 | 122.4 (2) |
C6—C7—H7 | 107.5 (12) | N2—C16—C17 | 119.4 (2) |
C9—C8—C14 | 121.9 (2) | C16—C17—H17A | 110.3 (18) |
C9—C8—C7 | 116.22 (19) | C16—C17—H17B | 113.6 (19) |
C14—C8—C7 | 121.85 (19) | H17A—C17—H17B | 104 (3) |
C8—C9—N1 | 117.23 (19) | C16—C17—H17C | 110.7 (17) |
C8—C9—C15 | 128.6 (2) | H17A—C17—H17C | 105 (2) |
N1—C9—C15 | 114.2 (2) | H17B—C17—H17C | 113 (3) |
O4—C10—N1 | 121.0 (2) | C3—O1—C11 | 117.6 (2) |
O4—C10—N2 | 125.2 (2) | C14—O2—C12 | 116.6 (2) |
N1—C10—N2 | 113.75 (19) | C10—N1—C9 | 124.47 (19) |
O1—C11—H11A | 106.9 (18) | C10—N1—H1N | 114.2 (15) |
O1—C11—H11B | 103.1 (18) | C9—N1—H1N | 117.2 (15) |
H11A—C11—H11B | 112 (3) | C10—N2—C16 | 124.65 (18) |
O1—C11—H11C | 110 (2) | C10—N2—C7 | 116.39 (17) |
H11A—C11—H11C | 108 (3) | C16—N2—C7 | 118.87 (17) |
H11B—C11—H11C | 115 (3) | ||
C6—C1—C2—C3 | −0.4 (4) | C9—C8—C14—O2 | −179.7 (2) |
C1—C2—C3—O1 | −178.3 (2) | C7—C8—C14—O2 | −0.8 (3) |
C1—C2—C3—C4 | 1.4 (4) | C4—C3—O1—C11 | −0.3 (4) |
O1—C3—C4—C5 | 178.6 (2) | C2—C3—O1—C11 | 179.4 (3) |
C2—C3—C4—C5 | −1.0 (3) | O3—C14—O2—C12 | −1.2 (4) |
C3—C4—C5—C6 | −0.4 (3) | C8—C14—O2—C12 | 178.5 (2) |
C4—C5—C6—C1 | 1.4 (3) | C13—C12—O2—C14 | 87.1 (4) |
C4—C5—C6—C7 | 178.8 (2) | O4—C10—N1—C9 | −164.1 (2) |
C2—C1—C6—C5 | −1.0 (4) | N2—C10—N1—C9 | 16.4 (3) |
C2—C1—C6—C7 | −178.4 (2) | C8—C9—N1—C10 | −26.6 (3) |
C5—C6—C7—N2 | 22.6 (3) | C15—C9—N1—C10 | 153.2 (2) |
C1—C6—C7—N2 | −160.2 (2) | O4—C10—N2—C16 | 22.0 (3) |
C5—C6—C7—C8 | 145.0 (2) | N1—C10—N2—C16 | −158.49 (19) |
C1—C6—C7—C8 | −37.7 (3) | O4—C10—N2—C7 | −154.6 (2) |
N2—C7—C8—C9 | 41.5 (3) | N1—C10—N2—C7 | 24.9 (3) |
C6—C7—C8—C9 | −82.2 (2) | O5—C16—N2—C10 | −173.8 (2) |
N2—C7—C8—C14 | −137.50 (19) | C17—C16—N2—C10 | 8.2 (3) |
C6—C7—C8—C14 | 98.8 (2) | O5—C16—N2—C7 | 2.7 (3) |
C14—C8—C9—N1 | 173.31 (19) | C17—C16—N2—C7 | −175.3 (2) |
C7—C8—C9—N1 | −5.7 (3) | C8—C7—N2—C10 | −52.1 (2) |
C14—C8—C9—C15 | −6.4 (4) | C6—C7—N2—C10 | 73.3 (2) |
C7—C8—C9—C15 | 174.6 (2) | C8—C7—N2—C16 | 131.08 (19) |
C9—C8—C14—O3 | 0.0 (4) | C6—C7—N2—C16 | −103.5 (2) |
C7—C8—C14—O3 | 178.9 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
C17—H17B···O3i | 0.929 (4) | 2.515 (4) | 3.228 (4) | 133 (2) |
C15—H15B···O4ii | 0.911 (5) | 2.794 (7) | 3.553 (4) | 141 (2) |
N1—H1N···O4ii | 0.892 (6) | 2.024 (6) | 2.913 (3) | 174 (2) |
C4—H4···O1iii | 0.979 (6) | 2.572 (6) | 3.310 (3) | 132 (1) |
Symmetry codes: (i) −x+1, −y+1, −z; (ii) −x, −y+1, −z; (iii) x, −y+3/2, z+1/2. |
Experimental details
Crystal data | |
Chemical formula | C17H20N2O5 |
Mr | 332.35 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 293 |
a, b, c (Å) | 8.8387 (8), 20.2043 (18), 10.0232 (9) |
β (°) | 107.839 (2) |
V (Å3) | 1703.9 (3) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.10 |
Crystal size (mm) | 0.3 × 0.2 × 0.1 |
Data collection | |
Diffractometer | Bruker SMART CCD area-detector |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 17507, 3343, 2369 |
Rint | 0.045 |
(sin θ/λ)max (Å−1) | 0.617 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.058, 0.121, 1.10 |
No. of reflections | 3343 |
No. of parameters | 286 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.20, −0.17 |
Computer programs: SMART (Bruker, 1998), SMART, SAINT (Bruker, 1998), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), ORTEP-3 for Windows (Farrugia, 1997), WinGX (Farrugia, 1999).
D—H···A | D—H | H···A | D···A | D—H···A |
C17—H17B···O3i | 0.929 (4) | 2.515 (4) | 3.228 (4) | 133 (2) |
C15—H15B···O4ii | 0.911 (5) | 2.794 (7) | 3.553 (4) | 141 (2) |
N1—H1N···O4ii | 0.892 (6) | 2.024 (6) | 2.913 (3) | 174 (2) |
C4—H4···O1iii | 0.979 (6) | 2.572 (6) | 3.310 (3) | 132 (1) |
Symmetry codes: (i) −x+1, −y+1, −z; (ii) −x, −y+1, −z; (iii) x, −y+3/2, z+1/2. |
4-Aryldihydropyrimidines (DHPMs) represent a heterocyclic system of remarkable pharmacological efficiency. They have recently emerged as important target molecules due to their therapeutic and medicinal properties (Kappe, 2000) such as antiviral (Hurst et al., 1961), antimitotic (Mayer et al., 1999), and antihypertensive (Atwal et al., 1991). They are also the most studied class of organic calcium channel modulators (Kappe, 1998; Jauk et al., 2000) and since their introduction into clinical medicine in 1975, they have become almost indispensable for the treatment of cardiovascular diseases such as hypertension, cardiac arrhythmias, or angina (Janis et al., 1987). These inherently asymmetric compounds have been studied extensively to expand the existing structure-activity relationships and to get further insight into molecular interactions at the receptor-site level (Cho et al., 1989; Atwal et al., 1990; Rovnyak et al., 1992 and Grover et al., 1995).
The title compound (I) is a calcium antagonist and belongs to dihydropyrimidine heterocycles. In this molecule (Fig. 1) the substituted aryl ring is positioned axially, perpendicular to, and nearly bisects the boat-like dihydropyrimidine ring. This is evident as the dihedral angle between the planes of both ring systems is 84.92 (7)°. The 4-aryl substitutent (methoxy group) adopts a synperiplanar position. These features have been found mandatory for optimum calcium channel modulatory activity according to the recently proposed new binding-site model for this class of cardiovascular drugs (Rovnyak et al., 1995; Triggle et al., 1995). The exocyclic ester at C8 adopts a trans orientation with respect to C8—C9 double bond. DHPM's of this type are known to show conformational flexibility, where, the aryl ring and the ester group can rotate and the conformation of dihydropyrimidine ring can change (Kappe et al., 1997; Shishkin et al., 1997). The crystal structure is stabilized by intermolecular C—H···O and N—H···O hydrogen bonds (Fig. 2).