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Logo of actae2this articlesearchopen accesssubmitActa Crystallographica Section E: Crystallographic CommunicationsActa Crystallographica Section E: Crystallographic Communications
 
Acta Crystallogr E Crystallogr Commun. 2016 April 1; 72(Pt 4): 452–455.
Published online 2016 March 4. doi:  10.1107/S2056989016003583
PMCID: PMC4910333

Crystal structure of (E)-9-(4-nitro­benzyl­idene)-8,9-di­hydro­pyrido[2,3-d]pyrrolo­[1,2-a]pyrimidin-5(7H)-one

Abstract

The title compound, C17H12N4O3, a pyrido­pyrrolo­pyrimidine derivative, is almost planar. The nitro­benzene ring is inclined to the mean plane of the 8,9-di­hydro­pyrido[2,3-d]pyrrolo­[1,2-a]pyrimidin-5(7H)-one moiety (r.m.s. deviation = 0.023 Å) by 6.8 (1)°. In the crystal, mol­ecules are linked via C—H(...)O and C—H(...)N hydrogen bonds, forming layers parallel to (101).

Keywords: crystal structure, pyrido­pyrimidine, pyrido­pyrrolo­pyrimidine, 4-nitro­benzaldehyde, yl­idene derivative, hydrogen bonding

Chemical context  

Pyrido[2,3-d]pyrimidines, and their derivatives, are an important group of heterocyclic compounds that exhibit biological and pharmacological activities. For example, Le Corre et al. (2010  ) have produced a library of pyrido[2,3-d]py­rimi­dines designed as inhibitors of FGFR3 tyrosine kinase. Ramana Reddy et al. (2014  ) have shown that such compounds are potent inhibitors of cyclin-dependent Kinase 4 (CDK4) and AMPK-related Kinase 5 (ARK5). A series of pyrazolo [4,3-d]pyrimidin-7-ones were synthesizied to study their pyrido kinases (CDKs) inhibitory activities (Geffken et al. 2011  ). The anti­tumor activity of some new pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5-one derivatives have also been studied (El-Nassan, 2011  ), and the anti­tumor activity of pyrido[2,3-d]pyrimidine and pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine derivatives that induce apoptosis through G1 cell-cycle arrest have been reported on by Fares et al. (2014  ). The above observations prompted us to synthesize the title compound, which contains a pyrido[2,3-d]pyrimidin-4-one moiety, and we report herein on its crystal structure.

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Structural commentary  

In the mol­ecular structure of the title compound (Fig. 1  ), the three fused rings of the 8,9-di­hydro­pyrido[2,3-d]pyrrolo[1,2-a]pyrimidin-5(7H)-one moiety (N1–N3/C1–C10), are essentially planar (r.m.s. deviation = 0.023 Å), with the maximum deviation from the mean plane being 0.036 (2) Å for atom C8. The nitro­benzene ring (C12–C17) is inclined to this mean plane by 6.8 (1)°, while the nitro group (N4/O2/O3) is inclined to the benzene ring by 15.0 (3)°.

Figure 1
Mol­ecular structure of the title compound, showing the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

Supra­molecular features  

In the crystal, mol­ecules are linked via C—H(...)O and C—H(...)N hydrogen bonds, forming layers lying parallel to (101); see Fig. 2  and Table 1  . Within the layers there are An external file that holds a picture, illustration, etc.
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Object name is e-72-00452-efi2.jpg(21) graph-set motifs present (Fig. 2  ). The layers are separated by an average inter­planar distance of ca 3.4 Å, but there are no significant inter­layer inter­actions present (Fig. 3  ).

Figure 2
A view along the a axis of the crystal packing of the title compound. The hydrogen bonds are shown as dashed lines (see Table 1  ). For clarity, H atoms not involved in hydrogen bonding have been omitted.
Figure 3
A view along the b axis of the crystal packing of the title compound. The hydrogen bonds and inter­planar distances (of ca 3.4 Å) are shown as dashed lines (see Table 1  ). For clarity, H atoms not involved in hydrogen ...
Table 1
Hydrogen-bond geometry (Å, °)

Database survey  

A search of the Cambridge Structural Database (Version 5.37, update November 2015; Groom & Allen, 2014  ) was carried out for various substructures (S1 and S2; Fig. 4  ) resembling the title compound. For substructure S1 (8,9-di­hydro­pyrido[2,3-d]pyrrolo­[1,2-a]pyrimidin-5(7H)-one), no hits were obtained. For substructure S2 (4H-3λ2-pyrido[2,3-d]pyrimidin-4-one), seven hits were found. Two of these compounds have substructure S3 (pyrido[2′,3′:4,5]pyrimido[1,2-a]indol-5(11H)-one), viz 9-fluoro­pyrido[2′,3′:4,5]pyrimido[1,2-a]indole-5,11-dione (refcode NIJYIP; CCDC 269950; Hicks et al., 2005  ), and 9-bromo­pyrido[2′,3′:4,5]pyrimido[1,2-a]indole-5,11-dione (refcode NIJYOV; CCDC 218226; DiTusa, 2003  ). They are classed as tryptanthrins, which have been shown to have strong anti­bacterial activity, for example, against malaria (Hicks et al., 2005  ).

Figure 4
Substructures used for the database survey.

Synthesis and crystallization  

To a mixture of 2,3-tri­methyl­enepyrido[2,3-d]pyrimidin-4-one (0.094 g, 0.5 mmol) and p-nitro­benzaldehyde (0.094 g, 0.6 mmol) was added acetic acid (3 ml, 98%). This mixture was refluxed in an oil bath (ca. 423-433 K) for 5 h after which it was left to stand for 24 h. During this time a yellow precipitate formed. It was filtered and washed with distilled water, giving yellow crystals of the title compound (yield: 0.144 g, 0.45 mmol, 90%; m.p. 567–568 K). Yellow block-like crystals suitable for X-ray analysis were grown from a solution of ethanol:water (2:1) by slow evaporation at room temperature. The title product is insoluble in benzene, chloro­form, acetic acid, acetone, DMF, and DMSO, but soluble in tri­fluoro­acetic acid. 1H NMR (400MHz, CDCl3, δ, p.p.m., J/Hz): 3.15 (2H, td, J = 6.5; 2.9, β-CH2), 4.16 (2H, t, J = 6.5, γ-CH2), 7.44 (2H, d, J = 8.8, H-2′,6′), 7.60 (1H, dd, J = 7.9; 5.9, H-6), 7.83 (1H, t, J = 2.9, =CH), 7.98 (2H, d, J = 8.8, H-3′,5′), 8.63 (1H, dd, J = 5.9; 1.7, H-5), 9.00 (1H, dd, J = 7.9; 1.7, H-7). R f = 0.47 (chloro­form:methanol, 10:1).

Refinement  

Crystal data, data collection and structure refinement details are summarized in Table 2  . H atoms were placed in calculated positions and included in the final cycles of refinement using a riding-model approximation: C—H = 0.93–0.97 Å with U iso(H) = 1.2U eq(C).

Table 2
Experimental details

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S2056989016003583/su5283sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989016003583/su5283Isup2.hkl

CCDC reference: 1456732

Additional supporting information: crystallographic information; 3D view; checkCIF report

Acknowledgments

This work was supported by a Fundamental grant (FA-F7-T207: Theoretical aspects of formation of asymmetrical centers in biologically active heterocyclic mol­ecules) from the Academy of Sciences of the Republic of Uzbekistan.

supplementary crystallographic information

Crystal data

C17H12N4O3F(000) = 664
Mr = 320.31Dx = 1.483 Mg m3
Monoclinic, P21/cCu Kα radiation, λ = 1.54184 Å
a = 7.1755 (3) ÅCell parameters from 2842 reflections
b = 11.5855 (3) Åθ = 4.6–75.6°
c = 17.2515 (5) ŵ = 0.88 mm1
β = 90.360 (3)°T = 293 K
V = 1434.12 (8) Å3Block, yellow
Z = 40.20 × 0.18 × 0.15 mm

Data collection

Oxford Diffraction Xcalibur Ruby diffractometer2194 reflections with I > 2σ(I)
Detector resolution: 10.2576 pixels mm-1Rint = 0.045
ω scansθmax = 76.0°, θmin = 4.6°
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009)h = −8→9
Tmin = 0.928, Tmax = 1.000k = −7→14
10375 measured reflectionsl = −21→20
2965 independent reflections

Refinement

Refinement on F20 restraints
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.057H-atom parameters constrained
wR(F2) = 0.175w = 1/[σ2(Fo2) + (0.0826P)2 + 0.3825P] where P = (Fo2 + 2Fc2)/3
S = 1.08(Δ/σ)max < 0.001
2965 reflectionsΔρmax = 0.31 e Å3
217 parametersΔρmin = −0.20 e Å3

Special details

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
O10.7005 (3)−0.09081 (15)0.54727 (12)0.0677 (6)
O20.9284 (3)0.88109 (16)0.33072 (13)0.0718 (6)
O30.9755 (5)0.7632 (2)0.23673 (14)0.0913 (9)
N10.6413 (3)0.24377 (15)0.62105 (12)0.0462 (5)
N20.7312 (3)0.10238 (16)0.52922 (11)0.0446 (5)
N30.5181 (4)0.18637 (18)0.73866 (13)0.0584 (6)
N40.9345 (3)0.78291 (19)0.30362 (13)0.0560 (6)
C10.7062 (3)0.21345 (18)0.55449 (13)0.0428 (5)
C20.6831 (4)0.00730 (19)0.57260 (15)0.0471 (5)
C30.5521 (4)−0.0476 (2)0.70117 (16)0.0527 (6)
H30.5655−0.12530.68910.063*
C40.4772 (4)−0.0150 (2)0.76967 (16)0.0572 (7)
H40.4362−0.06980.80510.069*
C50.4631 (5)0.1021 (2)0.78581 (16)0.0611 (7)
H50.41140.12320.83300.073*
C60.5898 (3)0.15420 (19)0.66978 (14)0.0454 (5)
C70.6088 (3)0.03714 (19)0.64897 (13)0.0441 (5)
C80.7641 (3)0.29244 (19)0.49255 (13)0.0428 (5)
C90.8364 (4)0.2207 (2)0.42615 (14)0.0506 (6)
H9A0.96780.23560.41780.061*
H9B0.76850.23790.37870.061*
C100.8050 (4)0.0949 (2)0.45079 (15)0.0526 (6)
H10A0.71670.05720.41640.063*
H10B0.92130.05220.45030.063*
C110.7470 (3)0.4070 (2)0.50057 (14)0.0452 (5)
H110.69390.43080.54690.054*
C120.7990 (3)0.50060 (19)0.44770 (13)0.0422 (5)
C130.8910 (4)0.4833 (2)0.37725 (15)0.0502 (6)
H130.92310.40890.36210.060*
C140.9345 (4)0.5759 (2)0.33012 (14)0.0495 (6)
H140.99380.56430.28300.059*
C150.8886 (3)0.6858 (2)0.35404 (13)0.0459 (5)
C160.8010 (4)0.7066 (2)0.42325 (14)0.0474 (5)
H160.77320.78160.43850.057*
C170.7552 (3)0.6140 (2)0.46970 (14)0.0465 (5)
H170.69440.62700.51630.056*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.1034 (16)0.0362 (9)0.0640 (12)−0.0012 (9)0.0249 (11)−0.0063 (8)
O20.1033 (17)0.0415 (10)0.0708 (13)−0.0056 (10)0.0169 (12)0.0069 (9)
O30.151 (2)0.0669 (14)0.0568 (13)0.0001 (14)0.0446 (15)0.0151 (10)
N10.0638 (12)0.0332 (9)0.0419 (10)−0.0014 (8)0.0163 (9)−0.0002 (7)
N20.0558 (11)0.0365 (9)0.0416 (10)0.0003 (8)0.0106 (8)−0.0027 (7)
N30.0854 (16)0.0414 (11)0.0485 (12)0.0009 (10)0.0222 (11)0.0014 (9)
N40.0722 (14)0.0476 (11)0.0485 (12)−0.0036 (10)0.0120 (10)0.0120 (9)
C10.0499 (12)0.0336 (10)0.0448 (12)0.0002 (8)0.0075 (9)−0.0014 (8)
C20.0582 (13)0.0356 (11)0.0476 (13)−0.0007 (9)0.0096 (10)−0.0010 (9)
C30.0683 (15)0.0383 (11)0.0516 (14)−0.0024 (11)0.0052 (12)0.0048 (10)
C40.0755 (17)0.0467 (13)0.0496 (14)−0.0040 (12)0.0113 (12)0.0123 (11)
C50.087 (2)0.0504 (14)0.0460 (14)0.0001 (13)0.0224 (13)0.0072 (11)
C60.0562 (13)0.0387 (11)0.0414 (11)0.0005 (9)0.0095 (10)0.0026 (9)
C70.0517 (12)0.0374 (11)0.0433 (12)−0.0003 (9)0.0073 (10)0.0014 (9)
C80.0496 (12)0.0422 (12)0.0368 (11)−0.0013 (9)0.0102 (9)−0.0022 (9)
C90.0649 (14)0.0481 (12)0.0389 (12)−0.0027 (11)0.0120 (10)−0.0025 (10)
C100.0688 (16)0.0437 (12)0.0455 (13)−0.0001 (11)0.0116 (12)−0.0053 (10)
C110.0559 (13)0.0409 (11)0.0390 (11)0.0001 (9)0.0124 (9)0.0010 (9)
C120.0498 (12)0.0401 (11)0.0369 (11)−0.0017 (9)0.0083 (9)0.0012 (8)
C130.0695 (15)0.0378 (11)0.0435 (13)0.0005 (10)0.0154 (11)−0.0026 (9)
C140.0687 (15)0.0463 (12)0.0335 (11)−0.0020 (11)0.0165 (10)−0.0013 (9)
C150.0558 (13)0.0405 (11)0.0415 (12)−0.0039 (9)0.0040 (10)0.0074 (9)
C160.0604 (14)0.0377 (11)0.0440 (12)0.0016 (9)0.0095 (10)−0.0019 (9)
C170.0552 (13)0.0438 (12)0.0406 (12)0.0019 (10)0.0115 (10)−0.0006 (9)

Geometric parameters (Å, º)

O1—C21.225 (3)C8—C111.340 (3)
O2—N41.231 (3)C8—C91.510 (3)
O3—N41.214 (3)C9—C101.535 (3)
N1—C11.291 (3)C9—H9A0.9700
N1—C61.387 (3)C9—H9B0.9700
N2—C11.371 (3)C10—H10A0.9700
N2—C21.377 (3)C10—H10B0.9700
N2—C101.459 (3)C11—C121.467 (3)
N3—C51.332 (3)C11—H110.9300
N3—C61.350 (3)C12—C131.401 (3)
N4—C151.461 (3)C12—C171.404 (3)
C1—C81.469 (3)C13—C141.383 (3)
C2—C71.466 (3)C13—H130.9300
C3—C41.355 (4)C14—C151.379 (3)
C3—C71.394 (3)C14—H140.9300
C3—H30.9300C15—C161.374 (3)
C4—C51.389 (4)C16—C171.380 (3)
C4—H40.9300C16—H160.9300
C5—H50.9300C17—H170.9300
C6—C71.410 (3)
C1—N1—C6115.76 (19)C8—C9—H9A110.7
C1—N2—C2123.0 (2)C10—C9—H9A110.7
C1—N2—C10113.55 (19)C8—C9—H9B110.7
C2—N2—C10123.40 (19)C10—C9—H9B110.7
C5—N3—C6116.8 (2)H9A—C9—H9B108.8
O3—N4—O2123.0 (2)N2—C10—C9104.79 (18)
O3—N4—C15118.5 (2)N2—C10—H10A110.8
O2—N4—C15118.5 (2)C9—C10—H10A110.8
N1—C1—N2125.9 (2)N2—C10—H10B110.8
N1—C1—C8125.7 (2)C9—C10—H10B110.8
N2—C1—C8108.39 (19)H10A—C10—H10B108.9
O1—C2—N2121.5 (2)C8—C11—C12130.1 (2)
O1—C2—C7125.3 (2)C8—C11—H11114.9
N2—C2—C7113.18 (19)C12—C11—H11114.9
C4—C3—C7119.1 (2)C13—C12—C17118.4 (2)
C4—C3—H3120.4C13—C12—C11123.8 (2)
C7—C3—H3120.4C17—C12—C11117.8 (2)
C3—C4—C5118.5 (2)C14—C13—C12120.5 (2)
C3—C4—H4120.8C14—C13—H13119.7
C5—C4—H4120.8C12—C13—H13119.7
N3—C5—C4124.8 (3)C15—C14—C13119.0 (2)
N3—C5—H5117.6C15—C14—H14120.5
C4—C5—H5117.6C13—C14—H14120.5
N3—C6—N1115.5 (2)C16—C15—C14122.3 (2)
N3—C6—C7121.8 (2)C16—C15—N4119.2 (2)
N1—C6—C7122.6 (2)C14—C15—N4118.5 (2)
C3—C7—C6118.9 (2)C15—C16—C17118.7 (2)
C3—C7—C2121.6 (2)C15—C16—H16120.7
C6—C7—C2119.5 (2)C17—C16—H16120.7
C11—C8—C1121.0 (2)C16—C17—C12121.1 (2)
C11—C8—C9131.0 (2)C16—C17—H17119.5
C1—C8—C9108.02 (19)C12—C17—H17119.5
C8—C9—C10105.11 (19)
C6—N1—C1—N2−1.3 (4)N1—C1—C8—C11−2.2 (4)
C6—N1—C1—C8178.0 (2)N2—C1—C8—C11177.2 (2)
C2—N2—C1—N12.0 (4)N1—C1—C8—C9178.3 (2)
C10—N2—C1—N1179.3 (2)N2—C1—C8—C9−2.4 (3)
C2—N2—C1—C8−177.4 (2)C11—C8—C9—C10−175.8 (3)
C10—N2—C1—C8−0.1 (3)C1—C8—C9—C103.7 (3)
C1—N2—C2—O1177.2 (3)C1—N2—C10—C92.5 (3)
C10—N2—C2—O10.2 (4)C2—N2—C10—C9179.7 (2)
C1—N2—C2—C7−1.9 (4)C8—C9—C10—N2−3.7 (3)
C10—N2—C2—C7−178.9 (2)C1—C8—C11—C12178.5 (2)
C7—C3—C4—C5−1.2 (5)C9—C8—C11—C12−2.1 (5)
C6—N3—C5—C41.1 (5)C8—C11—C12—C13−4.0 (4)
C3—C4—C5—N30.0 (5)C8—C11—C12—C17176.6 (3)
C5—N3—C6—N1178.4 (3)C17—C12—C13—C14−1.1 (4)
C5—N3—C6—C7−1.0 (4)C11—C12—C13—C14179.6 (3)
C1—N1—C6—N3−178.6 (2)C12—C13—C14—C151.0 (4)
C1—N1—C6—C70.8 (4)C13—C14—C15—C160.0 (4)
C4—C3—C7—C61.2 (4)C13—C14—C15—N4−179.7 (2)
C4—C3—C7—C2−177.2 (3)O3—N4—C15—C16−165.0 (3)
N3—C6—C7—C3−0.1 (4)O2—N4—C15—C1614.5 (4)
N1—C6—C7—C3−179.4 (2)O3—N4—C15—C1414.8 (4)
N3—C6—C7—C2178.4 (2)O2—N4—C15—C14−165.7 (3)
N1—C6—C7—C2−1.0 (4)C14—C15—C16—C17−1.0 (4)
O1—C2—C7—C30.8 (4)N4—C15—C16—C17178.8 (2)
N2—C2—C7—C3179.9 (2)C15—C16—C17—C120.9 (4)
O1—C2—C7—C6−177.7 (3)C13—C12—C17—C160.1 (4)
N2—C2—C7—C61.4 (3)C11—C12—C17—C16179.5 (2)

Hydrogen-bond geometry (Å, º)

D—H···AD—HH···AD···AD—H···A
C3—H3···N3i0.932.583.292 (3)133
C4—H4···N1i0.932.573.480 (3)166
C13—H13···O3ii0.932.513.363 (3)153
C16—H16···O1iii0.932.453.259 (3)145

Symmetry codes: (i) −x+1, y−1/2, −z+3/2; (ii) −x+2, y−1/2, −z+1/2; (iii) x, y+1, z.

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