Ethyl 1,6-dimethyl-2-oxo-4-(quinolin-4-yl)-1,2,3,4-tetra-hydro-pyrimidine-5-carboxyl-ate.

In the title compound, C(18)H(19)N(3)O(3), the tetra-hydro-pyrimidone ring adopts a distorted boat conformation. In the crystal structure, inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into centrosymmetric dimers, which are further linked via inter-molecular C-H⋯π inter-actions. In addition, an intra-molecular C-H⋯O hydrogen bond occurs.

Related literature

It has been proposed that the combination of the biologically active dihydro­pyrimidine subunit with a DNA inter­calator (Waring, 2006 ▶; Hannon, 2007 ▶; Ihmels & Otto, 2005 ▶) may lead to a new class of DNA-targeting drugs (Neidle & Thurston, 2005 ▶; Braña et al., 2001 ▶). Thus, a classical DNA intercalator, namely quinoline (Denny, 2003 ▶; Kharatishvili et al., 1997 ▶; Aislabie et al., 1990 ▶), was employed as quinoline-4-carbaldehyde in the Biginelli (1893 ▶) reaction that leads to the title compound. For the biological activity of pyrimidine-containing compounds, see: Goldmann & Stoltefuss (1991 ▶); McKinstry & Reading (1944 ▶); Kappe (2000 ▶); Luo et al. (2004 ▶). For van der Waals radii, see: Zefirov & Zorky (1989 ▶).

Experimental

Crystal data

C18H19N3O3

M = 325.36

Triclinic,

a = 8.5039 (10) Å

b = 9.4637 (11) Å

c = 10.7503 (11) Å

α = 110.799 (10)°

β = 95.807 (9)°

γ = 97.339 (9)°

V = 792.07 (17) Å3

Z = 2

Mo Kα radiation

μ = 0.10 mm−1

T = 293 K

0.4 × 0.3 × 0.2 mm

Data collection

Oxford Diffraction Xcalibur diffractometer with Sapphire3 detector

Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009 ▶) T min = 0.975, T max = 1

8517 measured reflections

4607 independent reflections

2810 reflections with I > 2σ(I)

R int = 0.017

Refinement

R[F 2 > 2σ(F 2)] = 0.044

wR(F 2) = 0.117

S = 0.99

4607 reflections

220 parameters

H-atom parameters constrained

Δρmax = 0.30 e Å−3

Δρmin = −0.17 e Å−3

Data collection: CrysAlis PRO (Oxford Diffraction, 2009 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: Superflip (Palatinus & Chapuis, 2007 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2009 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Crystal structure: contains datablocks I. DOI: 10.1107/S1600536810023482/lx2153sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810023482/lx2153Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C18H19N3O3	Z = 2
Mr = 325.36	F(000) = 344
Triclinic, P1	Dx = 1.364 Mg m−3
a = 8.5039 (10) Å	Mo Kα radiation, λ = 0.7107 Å
b = 9.4637 (11) Å	Cell parameters from 3300 reflections
c = 10.7503 (11) Å	θ = 3.1–32.4°
α = 110.799 (10)°	µ = 0.10 mm−1
β = 95.807 (9)°	T = 293 K
γ = 97.339 (9)°	Prism, colorless
V = 792.07 (17) Å3	0.4 × 0.3 × 0.2 mm

Oxford Diffraction Xcalibur diffractometer with Sapphire3 detector	4607 independent reflections
graphite	2810 reflections with I > 2σ(I)
Detector resolution: 16.1827 pixels mm-1	Rint = 0.017
ω scans	θmax = 30.0°, θmin = 3.1°
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009)	h = −12→12
Tmin = 0.975, Tmax = 1	k = −14→13
8517 measured reflections	l = −14→15

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)] = 0.044	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.117	H-atom parameters constrained
S = 0.99	w = 1/[σ2(Fo2) + (0.060P)2] where P = (Fo2 + 2Fc2)/3
4607 reflections	(Δ/σ)max = 0.001
220 parameters	Δρmax = 0.30 e Å−3
0 restraints	Δρmin = −0.17 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.

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
O1	0.27163 (12)	0.04049 (12)	0.18120 (11)	0.0531 (3)
O2	0.06327 (12)	−0.03288 (11)	0.26749 (11)	0.0499 (3)
O3	−0.17806 (12)	0.43713 (11)	0.03648 (11)	0.0505 (3)
N1	−0.19236 (12)	0.24916 (11)	0.12189 (11)	0.0342 (2)
N2	0.05174 (13)	0.36177 (12)	0.09001 (11)	0.0392 (3)
H2	0.1019	0.4088	0.0464	0.047*
N3	0.34211 (15)	0.63743 (12)	0.56698 (12)	0.0471 (3)
C1	0.14609 (14)	0.29466 (13)	0.16757 (12)	0.0315 (3)
H1	0.2345	0.2599	0.1197	0.038*
C2	0.04233 (15)	0.15552 (12)	0.17321 (12)	0.0317 (3)
C3	−0.11880 (15)	0.13846 (13)	0.15232 (12)	0.0324 (3)
C4	−0.10723 (16)	0.35587 (13)	0.08131 (13)	0.0355 (3)
C5	0.21887 (13)	0.41308 (12)	0.30752 (12)	0.0297 (3)
C6	0.16516 (16)	0.40622 (14)	0.42047 (13)	0.0377 (3)
H6	0.0850	0.3261	0.4139	0.045*
C7	0.23041 (18)	0.51977 (16)	0.54688 (15)	0.0467 (3)
H7	0.1913	0.5106	0.6219	0.056*
C8	0.40063 (15)	0.64740 (14)	0.45630 (14)	0.0385 (3)
C9	0.52172 (17)	0.77391 (15)	0.47649 (16)	0.0497 (4)
H9	0.5580	0.8462	0.5631	0.060*
C10	0.58558 (18)	0.79118 (17)	0.37115 (18)	0.0562 (4)
H10	0.6645	0.8754	0.3856	0.067*
C11	0.53288 (17)	0.68249 (17)	0.24086 (17)	0.0519 (4)
H11	0.5785	0.6942	0.1693	0.062*
C12	0.41510 (15)	0.55914 (15)	0.21731 (15)	0.0390 (3)
H12	0.3810	0.4886	0.1298	0.047*
C13	0.34461 (13)	0.53745 (13)	0.32394 (13)	0.0315 (3)
C14	0.13704 (16)	0.04890 (13)	0.20431 (13)	0.0356 (3)
C15	0.14436 (18)	−0.14639 (16)	0.29605 (17)	0.0488 (4)
H15B	0.2456	−0.0972	0.3555	0.059*
H15A	0.1659	−0.2207	0.2133	0.059*
C16	0.0369 (2)	−0.2227 (2)	0.3611 (2)	0.0799 (7)
H16B	0.0163	−0.1479	0.4426	0.120*
H16C	0.0869	−0.2987	0.3820	0.120*
H16A	−0.0625	−0.2712	0.3011	0.120*
C17	−0.23434 (17)	0.00572 (15)	0.15444 (17)	0.0485 (4)
H17C	−0.2872	0.0395	0.2319	0.073*
H17A	−0.1769	−0.0738	0.1587	0.073*
H17B	−0.3128	−0.0334	0.0741	0.073*
C18	−0.36752 (16)	0.23559 (17)	0.09982 (16)	0.0475 (4)
H18B	−0.4112	0.2070	0.1682	0.071*
H18A	−0.4111	0.1585	0.0127	0.071*
H18C	−0.3949	0.3324	0.1041	0.071*

	U11	U22	U33	U12	U13	U23
O1	0.0463 (6)	0.0626 (6)	0.0668 (8)	0.0204 (5)	0.0161 (5)	0.0384 (6)
O2	0.0498 (6)	0.0499 (6)	0.0725 (8)	0.0210 (4)	0.0171 (5)	0.0433 (5)
O3	0.0463 (6)	0.0575 (6)	0.0623 (7)	0.0094 (4)	0.0002 (5)	0.0421 (5)
N1	0.0347 (6)	0.0355 (5)	0.0355 (6)	0.0048 (4)	0.0016 (5)	0.0183 (4)
N2	0.0379 (6)	0.0459 (6)	0.0416 (7)	0.0001 (4)	−0.0010 (5)	0.0301 (5)
N3	0.0521 (7)	0.0459 (6)	0.0369 (7)	0.0003 (5)	0.0004 (5)	0.0124 (5)
C1	0.0329 (6)	0.0319 (6)	0.0324 (7)	0.0051 (4)	0.0036 (5)	0.0158 (5)
C2	0.0381 (7)	0.0275 (5)	0.0289 (6)	0.0034 (4)	0.0012 (5)	0.0116 (5)
C3	0.0402 (7)	0.0296 (6)	0.0269 (6)	0.0027 (5)	0.0009 (5)	0.0121 (5)
C4	0.0411 (7)	0.0368 (6)	0.0296 (7)	0.0030 (5)	−0.0012 (5)	0.0167 (5)
C5	0.0295 (6)	0.0295 (5)	0.0328 (7)	0.0078 (4)	0.0026 (5)	0.0146 (5)
C6	0.0416 (7)	0.0358 (6)	0.0359 (7)	0.0016 (5)	0.0053 (6)	0.0157 (5)
C7	0.0571 (9)	0.0482 (8)	0.0337 (8)	0.0036 (6)	0.0072 (7)	0.0159 (6)
C8	0.0363 (7)	0.0372 (7)	0.0396 (8)	0.0042 (5)	−0.0017 (6)	0.0144 (6)
C9	0.0433 (8)	0.0428 (8)	0.0538 (10)	−0.0051 (6)	−0.0066 (7)	0.0151 (6)
C10	0.0433 (9)	0.0512 (9)	0.0716 (12)	−0.0093 (6)	−0.0034 (8)	0.0291 (8)
C11	0.0426 (8)	0.0599 (9)	0.0618 (11)	0.0003 (7)	0.0095 (7)	0.0354 (8)
C12	0.0341 (7)	0.0441 (7)	0.0423 (8)	0.0059 (5)	0.0042 (6)	0.0210 (6)
C13	0.0271 (6)	0.0326 (6)	0.0380 (7)	0.0067 (4)	0.0012 (5)	0.0174 (5)
C14	0.0416 (7)	0.0309 (6)	0.0335 (7)	0.0057 (5)	0.0023 (6)	0.0123 (5)
C15	0.0510 (8)	0.0454 (8)	0.0646 (10)	0.0194 (6)	0.0091 (7)	0.0341 (7)
C16	0.0721 (12)	0.0777 (12)	0.136 (2)	0.0347 (10)	0.0407 (13)	0.0815 (13)
C17	0.0440 (8)	0.0434 (7)	0.0608 (10)	−0.0029 (6)	−0.0011 (7)	0.0289 (7)
C18	0.0372 (8)	0.0574 (8)	0.0553 (10)	0.0096 (6)	0.0063 (7)	0.0297 (7)

O1—C14	1.2018 (15)	C8—C9	1.4125 (18)
O2—C14	1.3377 (15)	C8—C13	1.4207 (18)
O2—C15	1.4504 (14)	C9—C10	1.356 (2)
O3—C4	1.2283 (14)	C9—H9	0.9300
N1—C4	1.3871 (15)	C10—C11	1.397 (2)
N1—C3	1.4019 (14)	C10—H10	0.9300
N1—C18	1.4662 (16)	C11—C12	1.3676 (18)
N2—C4	1.3380 (16)	C11—H11	0.9300
N2—C1	1.4538 (14)	C12—C13	1.4103 (18)
N2—H2	0.8600	C12—H12	0.9300
N3—C7	1.3061 (17)	C15—C16	1.471 (2)
N3—C8	1.3637 (18)	C15—H15B	0.9700
C1—C2	1.5122 (15)	C15—H15A	0.9700
C1—C5	1.5293 (17)	C16—H16B	0.9600
C1—H1	0.9800	C16—H16C	0.9600
C2—C3	1.3451 (17)	C16—H16A	0.9600
C2—C14	1.4735 (16)	C17—H17C	0.9600
C3—C17	1.5012 (16)	C17—H17A	0.9600
C5—C6	1.3591 (17)	C17—H17B	0.9600
C5—C13	1.4330 (15)	C18—H18B	0.9600
C6—C7	1.4022 (19)	C18—H18A	0.9600
C6—H6	0.9300	C18—H18C	0.9600
C7—H7	0.9300
C14—O2—C15	117.81 (10)	C9—C10—H10	120.0
C4—N1—C3	121.22 (10)	C11—C10—H10	120.0
C4—N1—C18	115.73 (10)	C12—C11—C10	120.81 (14)
C3—N1—C18	121.48 (10)	C12—C11—H11	119.6
C4—N2—C1	124.96 (10)	C10—C11—H11	119.6
C4—N2—H2	117.5	C11—C12—C13	120.95 (13)
C1—N2—H2	117.5	C11—C12—H12	119.5
C7—N3—C8	116.88 (12)	C13—C12—H12	119.5
N2—C1—C2	108.97 (10)	C12—C13—C8	117.82 (11)
N2—C1—C5	111.30 (9)	C12—C13—C5	124.39 (12)
C2—C1—C5	112.65 (10)	C8—C13—C5	117.79 (11)
N2—C1—H1	107.9	O1—C14—O2	122.41 (11)
C2—C1—H1	107.9	O1—C14—C2	123.48 (11)
C5—C1—H1	107.9	O2—C14—C2	114.03 (11)
C3—C2—C14	126.27 (11)	O2—C15—C16	106.99 (11)
C3—C2—C1	120.96 (10)	O2—C15—H15B	110.3
C14—C2—C1	112.77 (10)	C16—C15—H15B	110.3
C2—C3—N1	119.79 (10)	O2—C15—H15A	110.3
C2—C3—C17	125.97 (11)	C16—C15—H15A	110.3
N1—C3—C17	114.21 (11)	H15B—C15—H15A	108.6
O3—C4—N2	122.75 (11)	C15—C16—H16B	109.5
O3—C4—N1	120.25 (12)	C15—C16—H16C	109.5
N2—C4—N1	116.98 (10)	H16B—C16—H16C	109.5
C6—C5—C13	117.48 (11)	C15—C16—H16A	109.5
C6—C5—C1	121.55 (10)	H16B—C16—H16A	109.5
C13—C5—C1	120.96 (10)	H16C—C16—H16A	109.5
C5—C6—C7	120.17 (12)	C3—C17—H17C	109.5
C5—C6—H6	119.9	C3—C17—H17A	109.5
C7—C6—H6	119.9	H17C—C17—H17A	109.5
N3—C7—C6	124.77 (13)	C3—C17—H17B	109.5
N3—C7—H7	117.6	H17C—C17—H17B	109.5
C6—C7—H7	117.6	H17A—C17—H17B	109.5
N3—C8—C9	117.53 (13)	N1—C18—H18B	109.5
N3—C8—C13	122.88 (11)	N1—C18—H18A	109.5
C9—C8—C13	119.59 (13)	H18B—C18—H18A	109.5
C10—C9—C8	120.78 (14)	N1—C18—H18C	109.5
C10—C9—H9	119.6	H18B—C18—H18C	109.5
C8—C9—H9	119.6	H18A—C18—H18C	109.5
C9—C10—C11	120.05 (13)
C4—N2—C1—C2	29.78 (16)	C8—N3—C7—C6	−1.4 (2)
C4—N2—C1—C5	−95.05 (13)	C5—C6—C7—N3	0.6 (2)
N2—C1—C2—C3	−21.57 (16)	C7—N3—C8—C9	−179.87 (13)
C5—C1—C2—C3	102.47 (13)	C7—N3—C8—C13	0.41 (19)
N2—C1—C2—C14	159.04 (10)	N3—C8—C9—C10	179.93 (13)
C5—C1—C2—C14	−76.92 (13)	C13—C8—C9—C10	−0.3 (2)
C14—C2—C3—N1	−179.22 (11)	C8—C9—C10—C11	−0.6 (2)
C1—C2—C3—N1	1.47 (18)	C9—C10—C11—C12	1.0 (2)
C14—C2—C3—C17	−1.0 (2)	C10—C11—C12—C13	−0.6 (2)
C1—C2—C3—C17	179.65 (12)	C11—C12—C13—C8	−0.31 (18)
C4—N1—C3—C2	15.51 (18)	C11—C12—C13—C5	178.85 (12)
C18—N1—C3—C2	−179.37 (12)	N3—C8—C13—C12	−179.52 (11)
C4—N1—C3—C17	−162.87 (11)	C9—C8—C13—C12	0.77 (17)
C18—N1—C3—C17	2.25 (17)	N3—C8—C13—C5	1.27 (17)
C1—N2—C4—O3	165.93 (12)	C9—C8—C13—C5	−178.45 (11)
C1—N2—C4—N1	−15.95 (18)	C6—C5—C13—C12	178.85 (11)
C3—N1—C4—O3	169.42 (12)	C1—C5—C13—C12	−2.32 (17)
C18—N1—C4—O3	3.50 (18)	C6—C5—C13—C8	−1.99 (15)
C3—N1—C4—N2	−8.75 (18)	C1—C5—C13—C8	176.84 (10)
C18—N1—C4—N2	−174.68 (12)	C15—O2—C14—O1	−6.3 (2)
N2—C1—C5—C6	109.13 (12)	C15—O2—C14—C2	176.97 (11)
C2—C1—C5—C6	−13.61 (15)	C3—C2—C14—O1	155.76 (13)
N2—C1—C5—C13	−69.65 (13)	C1—C2—C14—O1	−24.89 (18)
C2—C1—C5—C13	167.60 (10)	C3—C2—C14—O2	−27.58 (19)
C13—C5—C6—C7	1.16 (17)	C1—C2—C14—O2	151.78 (11)
C1—C5—C6—C7	−177.67 (11)	C14—O2—C15—C16	−178.22 (14)

Cg1 is the centroid of the C8–C13 ring.

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O3i	0.86	2.03	2.8701 (16)	164
C17—H17A···O2	0.96	2.16	2.8187 (19)	124
C16—H16C···Cg1ii	0.96	2.66	3.603 (2)	168

Table 1

Hydrogen-bond geometry (Å, °)

Cg1 is the centroid of the C8–C13 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2⋯O3i	0.86	2.03	2.8701 (16)	164
C17—H17A⋯O2	0.96	2.16	2.8187 (19)	124
C16—H16C⋯Cg1ii	0.96	2.66	3.603 (2)	168

Symmetry codes: (i) ; (ii) .