organic compounds
5-Acetyl-4-(2,5-dimethoxyphenyl)-6-methyl-1-(prop-2-ynyl)-3,4-dihydropyrimidin-2(1H)-one
aLaboratoire de Chimie Bio-organique et Macromoléculaire, Faculté des Sciences et Techniques Guéliz, Marrakech, Morocco, bLaboratoire de Chimie Biomoléculaire et Médicinale, Faculté des Sciences Semlalia, Marrakech, Morocco, cLaboratoire de la Matière Condensée et des Nanostructures, Faculté des Sciences et Techniques Guéliz, Marrakech, Morocco, and dLaboratoire de Chimie du Solide Appliquée, Faculty of Sciences, Mohammed V University in Rabat, Avenue Ibn Battouta, BP 1014, Rabat, Morocco
*Correspondence e-mail: h_kaoukabi@yahoo.com
In the title compound, C18H20N2O4, the 3,4-dihydropyrimidin-2(1H)-one ring has a screw-boat conformation. The mean plane through this heterocycle is almost perpendicular to the prop-2-ynyl chain and to the benzene ring, with which it makes a dihedral angle of 87.63 (6)°. The plane through the acetyl group makes a dihedral angle of 33.11 (8)° with the mean plane of the heterocycle. There is an intramolecular C—H⋯O hydrogen bond present forming an S(6) ring motif. In the crystal, molecules are linked by C—H⋯O hydrogen bonds, forming layers parallel to the bc plane. There are also C—H⋯π interactions present within the layers.
CCDC reference: 1553623
Structure description
Dihydropyrimidinones (DHPMs) and their derivatives have received much attention because of their biological activities and widespread pharmacological activities, such as antiviral, antibacterial, antitumor and antihypertensive (Rovnyak et al., 1995). Some have been used successfully as calcium channel blockers, α1a-antagonists and neuropeptide Y (NPY) antagonists (Atwal et al., 1990). Several which contain the dihydropyrimidine core unit, have been isolated from marine sources. Most notable among these are the batzelladine which were found to be potent HIVgp-120-CD4 inhibitors (Snider et al., 1996).
In connection with our studies, we chose to work on DHPMs, which have six possible sites around the DHPM ring where modification/functionalization can be achieved. Therefore, we decided to explore the feasibility of alkylated DHPMs. Thus, this investigation had allowed us to describe a new efficient method for the preparation of new compounds with regioselective N1-alkylation and N1/N3-bis-alkylation of DHPMs analogues (Mohamadpour et al., 2016; Zare & Nasouri 2016).
The molecule of the title compound (Fig. 1) is built up from a 3,4-dihydropyrimidin-2(1H)-one ring linked to an acetyl group, a prop-2-ynyl chain and a 2,5-dimethoxyphenyl group. The dihydropyrimidine ring (atoms N1/N2/C3–C6) adopts a screw-boat conformation, as indicated by the puckering parameters: Q2 = 0.4086 (13) Å, θ = 69.29 (18)° and φ = 196.6 (2)°. The dihedral angle between the mean plane of the heterocycle and that of the benzene ring is 87.63 (6)°. The prop-2-ynyl chain is nearly perpendicular to the mean plane of the dihydropyrimidine ring, with a C9—C8—N1—C4 torsion angle of −72.09 (19)°. There is an intramolecular C—H⋯O hydrogen bond present, forming an S(6) ring motif (Fig. 1 and Table 1).
In the crystal, molecules are linked by C—H⋯O hydrogen bonds, forming layers parallel to the bc plane. There are also C—H⋯π interactions present within the layers (Fig. 2 and Table 1).
Synthesis and crystallization
The title compound was prepared in good yield (70%) through condensation of 5-acetyl-4-(2,5-dimethoxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one with propargyl bromide in the presence of potassium tert-butoxide in dry dimethylformamide at room temperature. The mixture was heated with stirring for 1 h. The crude product obtained was purified using a column packed with silica gel. The title compound was crystallized by slow evaporation from a solution in methanol (m.p. 428 K). 1H NMR (DMSO-d6): δ 2.08 (s, 3H, CH3CO), 2.50 (s, 3H, CH3), 3.28 (s, 1H, CH), 3.65 (s, 3H, OCH3), 3.76 (s, 3H, OCH3), 4.34–4.68 (m, 2H, –CH2–), 5.49 (s, 1H, H-4), 6.64–6.65 (s, 1H), 6.65–6.95 (m, 2H, C—Ar), 7.80 (s, 1H, N3—H). The signal due to N1—H was not observable in the 1H NMR spectrum. 13C NMR (DMSO-d6): δ 196.34 (CO), 153.19 (C-6), 152.25, 150.07, 146.45, 131.27, 113.29 (C-Ar), 112.30 (C-5), 80.51 (C-alkyl), 74.25 (CH-alkyl), 55.82 (OCH3), 55.34 (OCH3), 47.72 (C-4), 31.44 (–CH3-), 29.63 (CH3 at C-4′), 15.72 (CH3 at C-6).
Refinement
Crystal data, data collection and structure .
details are summarized in Table 2
|
Structural data
CCDC reference: 1553623
https://doi.org/10.1107/S2414314617008161/su4154sup1.cif
contains datablock I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314617008161/su4154Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2414314617008161/su4154Isup3.cml
Data collection: APEX2 (Bruker, 2009); cell
SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015b) and publCIF (Westrip, 2010).C18H20N2O4 | F(000) = 348 |
Mr = 328.36 | Dx = 1.302 Mg m−3 |
Triclinic, P1 | Melting point: 428 K |
a = 8.5948 (15) Å | Mo Kα radiation, λ = 0.71073 Å |
b = 10.1942 (16) Å | Cell parameters from 4005 reflections |
c = 10.2572 (17) Å | θ = 2.5–27.9° |
α = 74.930 (7)° | µ = 0.09 mm−1 |
β = 75.306 (7)° | T = 296 K |
γ = 89.866 (7)° | Prism, colourless |
V = 837.5 (2) Å3 | 0.35 × 0.27 × 0.24 mm |
Z = 2 |
Bruker X8 APEX diffractometer | 4005 independent reflections |
Radiation source: fine-focus sealed tube | 3333 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.043 |
φ and ω scans | θmax = 27.9°, θmin = 2.5° |
Absorption correction: multi-scan (SADABS; Krause et al., 2015) | h = −11→11 |
Tmin = 0.587, Tmax = 0.746 | k = −13→13 |
25426 measured reflections | l = −13→13 |
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)] = 0.049 | Hydrogen site location: mixed |
wR(F2) = 0.147 | H-atom parameters constrained |
S = 1.05 | w = 1/[σ2(Fo2) + (0.0844P)2 + 0.1806P] where P = (Fo2 + 2Fc2)/3 |
4005 reflections | (Δ/σ)max < 0.001 |
221 parameters | Δρmax = 0.35 e Å−3 |
0 restraints | Δρmin = −0.24 e Å−3 |
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. |
x | y | z | Uiso*/Ueq | ||
C1 | 0.5494 (2) | 0.41801 (18) | 0.84088 (19) | 0.0558 (4) | |
H1A | 0.5399 | 0.3684 | 0.9362 | 0.084* | |
H1B | 0.5578 | 0.5139 | 0.8323 | 0.084* | |
H1C | 0.6439 | 0.3936 | 0.7813 | 0.084* | |
C2 | 0.40293 (17) | 0.38370 (13) | 0.79841 (14) | 0.0377 (3) | |
C3 | 0.33613 (15) | 0.49333 (11) | 0.70720 (13) | 0.0306 (3) | |
C4 | 0.18163 (15) | 0.48869 (12) | 0.69912 (13) | 0.0340 (3) | |
C5 | 0.24167 (17) | 0.68119 (13) | 0.48927 (14) | 0.0365 (3) | |
C6 | 0.44451 (14) | 0.61836 (11) | 0.62095 (12) | 0.0300 (3) | |
H6 | 0.5553 | 0.5908 | 0.5986 | 0.036* | |
C7 | 0.0526 (2) | 0.38038 (17) | 0.78715 (19) | 0.0554 (4) | |
H7A | 0.0955 | 0.3151 | 0.8526 | 0.083* | |
H7B | 0.0153 | 0.3355 | 0.7281 | 0.083* | |
H7C | −0.0356 | 0.4210 | 0.8371 | 0.083* | |
C8 | −0.03898 (17) | 0.61963 (18) | 0.61831 (17) | 0.0489 (4) | |
H8A | −0.0515 | 0.6812 | 0.5325 | 0.059* | |
H8B | −0.0998 | 0.5345 | 0.6335 | 0.059* | |
C9 | −0.1038 (2) | 0.67832 (18) | 0.73473 (18) | 0.0537 (4) | |
C10 | −0.1570 (3) | 0.7250 (2) | 0.8278 (2) | 0.0772 (6) | |
H10 | −0.1994 | 0.7623 | 0.9020 | 0.093* | |
C11 | 0.44181 (14) | 0.73281 (11) | 0.69222 (13) | 0.0291 (3) | |
C12 | 0.32378 (15) | 0.73776 (12) | 0.80983 (13) | 0.0335 (3) | |
H12 | 0.2438 | 0.6672 | 0.8507 | 0.040* | |
C13 | 0.32220 (17) | 0.84719 (13) | 0.86881 (14) | 0.0363 (3) | |
C14 | 0.44185 (18) | 0.95137 (13) | 0.80889 (15) | 0.0398 (3) | |
H14 | 0.4420 | 1.0242 | 0.8478 | 0.048* | |
C15 | 0.56169 (17) | 0.94741 (13) | 0.69075 (15) | 0.0393 (3) | |
H15 | 0.6424 | 1.0175 | 0.6512 | 0.047* | |
C16 | 0.56234 (14) | 0.83999 (12) | 0.63111 (13) | 0.0324 (3) | |
C17 | 0.79489 (19) | 0.93614 (16) | 0.44539 (19) | 0.0546 (4) | |
H17A | 0.7447 | 1.0193 | 0.4175 | 0.082* | |
H17B | 0.8642 | 0.9166 | 0.3642 | 0.082* | |
H17C | 0.8573 | 0.9456 | 0.5083 | 0.082* | |
C18 | 0.1949 (3) | 0.94388 (18) | 1.0534 (2) | 0.0659 (5) | |
H18A | 0.2918 | 0.9453 | 1.0834 | 0.099* | |
H18B | 0.1031 | 0.9261 | 1.1332 | 0.099* | |
H18C | 0.1879 | 1.0304 | 0.9905 | 0.099* | |
N1 | 0.13235 (13) | 0.59452 (12) | 0.60294 (12) | 0.0377 (3) | |
N2 | 0.39836 (13) | 0.66749 (11) | 0.48902 (11) | 0.0351 (3) | |
H2 | 0.4624 | 0.7272 | 0.4224 | 0.042* | |
O1 | 0.34499 (16) | 0.26674 (10) | 0.83972 (14) | 0.0602 (3) | |
O2 | 0.19764 (15) | 0.75801 (11) | 0.39413 (12) | 0.0547 (3) | |
O3 | 0.19759 (15) | 0.84067 (11) | 0.98417 (12) | 0.0558 (3) | |
O4 | 0.67395 (11) | 0.82756 (10) | 0.51386 (11) | 0.0428 (3) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0623 (10) | 0.0530 (9) | 0.0600 (10) | 0.0125 (7) | −0.0329 (8) | −0.0122 (7) |
C2 | 0.0458 (7) | 0.0295 (6) | 0.0356 (6) | 0.0060 (5) | −0.0065 (5) | −0.0090 (5) |
C3 | 0.0346 (6) | 0.0238 (5) | 0.0328 (6) | −0.0012 (4) | −0.0066 (5) | −0.0085 (4) |
C4 | 0.0359 (6) | 0.0314 (6) | 0.0345 (6) | −0.0041 (5) | −0.0072 (5) | −0.0106 (5) |
C5 | 0.0444 (7) | 0.0337 (6) | 0.0354 (6) | 0.0004 (5) | −0.0147 (5) | −0.0123 (5) |
C6 | 0.0290 (6) | 0.0268 (5) | 0.0333 (6) | 0.0007 (4) | −0.0068 (5) | −0.0080 (5) |
C7 | 0.0465 (8) | 0.0522 (9) | 0.0584 (10) | −0.0194 (7) | −0.0119 (7) | −0.0009 (7) |
C8 | 0.0353 (7) | 0.0679 (10) | 0.0505 (8) | 0.0064 (7) | −0.0175 (6) | −0.0219 (7) |
C9 | 0.0421 (8) | 0.0653 (10) | 0.0563 (9) | 0.0110 (7) | −0.0154 (7) | −0.0186 (8) |
C10 | 0.0824 (15) | 0.0867 (15) | 0.0677 (12) | 0.0240 (12) | −0.0142 (11) | −0.0352 (11) |
C11 | 0.0297 (6) | 0.0244 (5) | 0.0346 (6) | 0.0000 (4) | −0.0133 (5) | −0.0056 (4) |
C12 | 0.0358 (6) | 0.0269 (5) | 0.0365 (6) | −0.0050 (5) | −0.0085 (5) | −0.0071 (5) |
C13 | 0.0425 (7) | 0.0311 (6) | 0.0358 (6) | −0.0003 (5) | −0.0099 (5) | −0.0100 (5) |
C14 | 0.0471 (7) | 0.0291 (6) | 0.0478 (8) | −0.0022 (5) | −0.0172 (6) | −0.0134 (5) |
C15 | 0.0373 (7) | 0.0284 (6) | 0.0514 (8) | −0.0075 (5) | −0.0150 (6) | −0.0060 (5) |
C16 | 0.0281 (6) | 0.0296 (6) | 0.0387 (6) | −0.0005 (4) | −0.0118 (5) | −0.0047 (5) |
C17 | 0.0374 (8) | 0.0484 (8) | 0.0628 (10) | −0.0105 (6) | −0.0009 (7) | −0.0006 (7) |
C18 | 0.0874 (14) | 0.0520 (9) | 0.0549 (10) | −0.0101 (9) | 0.0030 (9) | −0.0295 (8) |
N1 | 0.0318 (5) | 0.0425 (6) | 0.0395 (6) | 0.0005 (4) | −0.0116 (5) | −0.0098 (5) |
N2 | 0.0371 (6) | 0.0350 (5) | 0.0298 (5) | −0.0051 (4) | −0.0048 (4) | −0.0066 (4) |
O1 | 0.0716 (8) | 0.0285 (5) | 0.0726 (8) | 0.0021 (5) | −0.0178 (6) | −0.0008 (5) |
O2 | 0.0619 (7) | 0.0534 (6) | 0.0487 (6) | −0.0029 (5) | −0.0290 (5) | 0.0006 (5) |
O3 | 0.0667 (7) | 0.0448 (6) | 0.0493 (6) | −0.0138 (5) | 0.0084 (5) | −0.0241 (5) |
O4 | 0.0338 (5) | 0.0388 (5) | 0.0482 (6) | −0.0059 (4) | −0.0014 (4) | −0.0078 (4) |
C1—C2 | 1.502 (2) | C9—C10 | 1.167 (3) |
C1—H1A | 0.9600 | C10—H10 | 0.9300 |
C1—H1B | 0.9600 | C11—C12 | 1.3775 (18) |
C1—H1C | 0.9600 | C11—C16 | 1.4070 (16) |
C2—O1 | 1.2174 (17) | C12—C13 | 1.3991 (17) |
C2—C3 | 1.4764 (17) | C12—H12 | 0.9300 |
C3—C4 | 1.3529 (18) | C13—O3 | 1.3668 (17) |
C3—C6 | 1.5087 (16) | C13—C14 | 1.3814 (19) |
C4—N1 | 1.4046 (17) | C14—C15 | 1.387 (2) |
C4—C7 | 1.4978 (18) | C14—H14 | 0.9300 |
C5—O2 | 1.2237 (16) | C15—C16 | 1.3856 (18) |
C5—N2 | 1.3530 (18) | C15—H15 | 0.9300 |
C5—N1 | 1.3912 (18) | C16—O4 | 1.3698 (16) |
C6—N2 | 1.4691 (16) | C17—O4 | 1.4246 (17) |
C6—C11 | 1.5267 (16) | C17—H17A | 0.9600 |
C6—H6 | 0.9800 | C17—H17B | 0.9600 |
C7—H7A | 0.9600 | C17—H17C | 0.9600 |
C7—H7B | 0.9600 | C18—O3 | 1.4110 (18) |
C7—H7C | 0.9600 | C18—H18A | 0.9600 |
C8—C9 | 1.458 (2) | C18—H18B | 0.9600 |
C8—N1 | 1.4697 (18) | C18—H18C | 0.9600 |
C8—H8A | 0.9700 | N2—H2 | 0.8572 |
C8—H8B | 0.9700 | ||
C2—C1—H1A | 109.5 | C12—C11—C16 | 119.07 (11) |
C2—C1—H1B | 109.5 | C12—C11—C6 | 122.88 (10) |
H1A—C1—H1B | 109.5 | C16—C11—C6 | 118.01 (11) |
C2—C1—H1C | 109.5 | C11—C12—C13 | 121.09 (11) |
H1A—C1—H1C | 109.5 | C11—C12—H12 | 119.5 |
H1B—C1—H1C | 109.5 | C13—C12—H12 | 119.5 |
O1—C2—C3 | 122.78 (13) | O3—C13—C14 | 125.23 (12) |
O1—C2—C1 | 118.74 (13) | O3—C13—C12 | 115.32 (12) |
C3—C2—C1 | 118.48 (12) | C14—C13—C12 | 119.45 (12) |
C4—C3—C2 | 123.36 (11) | C13—C14—C15 | 120.03 (12) |
C4—C3—C6 | 118.25 (11) | C13—C14—H14 | 120.0 |
C2—C3—C6 | 118.38 (11) | C15—C14—H14 | 120.0 |
C3—C4—N1 | 118.96 (11) | C16—C15—C14 | 120.61 (12) |
C3—C4—C7 | 125.79 (13) | C16—C15—H15 | 119.7 |
N1—C4—C7 | 115.24 (12) | C14—C15—H15 | 119.7 |
O2—C5—N2 | 123.43 (13) | O4—C16—C15 | 125.03 (11) |
O2—C5—N1 | 121.63 (13) | O4—C16—C11 | 115.24 (11) |
N2—C5—N1 | 114.83 (11) | C15—C16—C11 | 119.73 (12) |
N2—C6—C3 | 107.64 (10) | O4—C17—H17A | 109.5 |
N2—C6—C11 | 110.29 (9) | O4—C17—H17B | 109.5 |
C3—C6—C11 | 114.99 (10) | H17A—C17—H17B | 109.5 |
N2—C6—H6 | 107.9 | O4—C17—H17C | 109.5 |
C3—C6—H6 | 107.9 | H17A—C17—H17C | 109.5 |
C11—C6—H6 | 107.9 | H17B—C17—H17C | 109.5 |
C4—C7—H7A | 109.5 | O3—C18—H18A | 109.5 |
C4—C7—H7B | 109.5 | O3—C18—H18B | 109.5 |
H7A—C7—H7B | 109.5 | H18A—C18—H18B | 109.5 |
C4—C7—H7C | 109.5 | O3—C18—H18C | 109.5 |
H7A—C7—H7C | 109.5 | H18A—C18—H18C | 109.5 |
H7B—C7—H7C | 109.5 | H18B—C18—H18C | 109.5 |
C9—C8—N1 | 111.79 (12) | C5—N1—C4 | 122.27 (11) |
C9—C8—H8A | 109.3 | C5—N1—C8 | 116.49 (12) |
N1—C8—H8A | 109.3 | C4—N1—C8 | 121.24 (12) |
C9—C8—H8B | 109.3 | C5—N2—C6 | 120.61 (11) |
N1—C8—H8B | 109.3 | C5—N2—H2 | 112.9 |
H8A—C8—H8B | 107.9 | C6—N2—H2 | 117.8 |
C10—C9—C8 | 179.4 (2) | C13—O3—C18 | 117.94 (13) |
C9—C10—H10 | 180.0 | C16—O4—C17 | 117.23 (11) |
Cg1 is the centroid of ring C11-C16. |
D—H···A | D—H | H···A | D···A | D—H···A |
C7—H7A···O1 | 0.96 | 2.18 | 2.881 (2) | 129 |
C10—H10···O1i | 0.93 | 2.57 | 3.406 (2) | 150 |
C14—H14···O1ii | 0.93 | 2.60 | 3.393 (2) | 144 |
C15—H15···O2iii | 0.93 | 2.55 | 3.437 (2) | 161 |
C17—H17A···Cg1iii | 0.96 | 2.77 | 3.601 (2) | 146 |
Symmetry codes: (i) −x, −y+1, −z+2; (ii) x, y+1, z; (iii) −x+1, −y+2, −z+1. |
Acknowledgements
The authors thank the Unit of Support for Technical and Scientific Research (UATRS, CNRST) for the X-ray measurements.
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