organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2414-3146

3-Acetyl-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one

aLaboratoire de Chimie Organique Hétérocyclique URAC 21, Pôle de Compétence Pharmacochimie, Av. Ibn Battouta, BP 1014, Faculté des Sciences, Université Mohammed V, Rabat, Morocco, and bDepartment of Chemistry, Tulane University, New Orleans, LA 70118, USA
*Correspondence e-mail: lahmidi_sanae@yahoo.fr

Edited by M. Weil, Vienna University of Technology, Austria (Received 21 June 2017; accepted 3 July 2017; online 18 July 2017)

In the title compound, C11H10N2O2, the pyrido­pyrimidine moiety deviates slightly from planarity. In the crystal, mol­ecules stack along the a-axis direction assisted by ππ stacking inter­actions and C—H⋯O hydrogen bonds. The stacks are associated in centrosymmetric pairs through C—H⋯N hydrogen bonds.

3D view (loading...)
[Scheme 3D1]
Chemical scheme
[Scheme 1]

Structure description

Pyrido[1,2-a]pyrimidine derivatives exhibit a broad range of biological activities (Harriman et al., 2003[Harriman, G. C. B., Chi, S., Zhang, M., Crowe, A., Bennett, R. A. & Parsons, I. (2003). Tetrahedron Lett. 44, 3659-3662.]), including anti­bacterial (Nargund et al., 1991[Nargund, L. V. G., Reddy, Y. S. R. & Jose, R. (1991). Indian Drugs, 29, 45-46.]) and anti­malarial agents (Mane et al., 2014[Mane, U. R., Mohanakrishnan, D., Sahal, D., Murumkar, P. R., Giridhar, R. & Yadav, M. R. (2014). Eur. J. Med. Chem. 79, 422-435.]). Also, the anti­allergic agent ramastine (Awouters et al., 1986[Awouters, F., Vermeire, J., Smeyers, F., Vermote, P., van Beek, R. & Niemegeers, C. J. E. (1986). Drug Dev. Res. 8, 95-102.]), the anti­depressant lusaperidone (Kennis et al., 2000[Kennis, L. E. J., Bischoff, F. P., Mertens, C. J., Love, C. J., Van den Keybus, F. A. F., Pieters, S., Braeken, M., Megens, A. A. H. P. & Leysen, J. E. (2000). Bioorg. Med. Chem. Lett. 10, 71-74.]) and the tranquilizer pirenperone (Smith et al., 1995[Smith, R. L., Barrett, R. J. & Sanders-Bush, E. J. (1995). J. Pharmacol. Exp. Ther. 275, 1050-1057.]) derive from such aza-bridgehead-fused heterocyclic compounds. As part of our ongoing studies (Lahmidi et al., 2016[Lahmidi, S., El Ouasif, L., Jilalat, A. E., Al-Garadi, W., Essassi, E. M. & Mague, J. T. (2016). IUCrData, 1, x161978.]) of pyrido­pyrimidine derivatives, we report here the synthesis and structure of the title compound.

The pyrido­pyrimidine unit deviates slightly from planarity as indicated by the dihedral angle of 2.76 (5)° between the two constituent rings (Fig. 1[link]). The acetyl moiety is inclined to the pyrimidine ring by 41.21 (7)°. In the crystal, the mol­ecules form stacks along the a-axis direction through head-to-head ππ stacking inter­actions [centroid⋯centroid = 3.7715 (9) Å], which are reinforced by C10—H10A⋯O1i [symmetry code: (i) x + 1, y, z] hydrogen bonds (Table 1[link] and Fig. 2[link]). Pairs of stacks are associated through pairwise inversion-related C2—H2⋯N2ii [symmetry code: (ii) −x + 1, −y + 1, −z + 1] hydrogen bonds (Table 1[link] and Fig. 2[link]).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
C2—H2⋯N2i 0.997 (14) 2.494 (14) 3.4679 (15) 165.5 (11)
C5—H5⋯O1ii 0.955 (15) 2.349 (16) 3.1710 (14) 143.9 (12)
C10—H10A⋯O1iii 0.972 (16) 2.513 (17) 3.4153 (16) 154.5 (12)
Symmetry codes: (i) -x+1, -y+1, -z+1; (ii) -x, -y+1, -z; (iii) x+1, y, z.
[Figure 1]
Figure 1
The mol­ecular structure of the title compound, with displacement ellipsoids drawn at the 50% probability level.
[Figure 2]
Figure 2
The crystal packing viewed approximately along the a-axis direction, with C—H⋯O and C—H⋯N hydrogen bonds shown as black dashed lines and ππ stacking inter­actions shown as orange dashed lines.

Synthesis and crystallization

A mixture of 1-(2-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-3- yl)butane-1,3-dione (0.7 g, 2.86 mmol) and o-phenyl­enedi­amine (0.93 g, 8.58 mmol) was stirred in acetic acid (20 ml) at room temperature for 8 h. After completion of the reaction as monitored by thin-layer chromatography, the reaction mixture was cooled and the excess of acetic acid removed under reduced pressure. The residue was re-dissolved in di­chloro­methane and evaporated again. The solid obtained was filtered, washed with cold water and recrystallized from ethanol solution.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link].

Table 2
Experimental details

Crystal data
Chemical formula C11H10N2O2
Mr 202.21
Crystal system, space group Triclinic, P[\overline{1}]
Temperature (K) 100
a, b, c (Å) 3.7716 (6), 10.3959 (15), 12.3280 (18)
α, β, γ (°) 78.017 (2), 83.431 (2), 81.266 (2)
V3) 465.63 (12)
Z 2
Radiation type Mo Kα
μ (mm−1) 0.10
Crystal size (mm) 0.21 × 0.20 × 0.11
 
Data collection
Diffractometer Bruker SMART APEX CCD
Absorption correction Multi-scan (SADABS; Bruker, 2016[Bruker (2016). APEX3, SADABS and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.88, 0.99
No. of measured, independent and observed [I > 2σ(I)] reflections 9022, 2470, 1901
Rint 0.027
(sin θ/λ)max−1) 0.688
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.049, 0.136, 1.00
No. of reflections 2470
No. of parameters 176
H-atom treatment All H-atom parameters refined
Δρmax, Δρmin (e Å−3) 0.49, −0.23
Computer programs: APEX3 and SAINT (Bruker, 2016[Bruker (2016). APEX3, SADABS and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXT (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2014 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]), DIAMOND (Brandenburg & Putz, 2012[Brandenburg, K. & Putz, H. (2012). DIAMOND. Crystal Impact GbR, Bonn, Germany.]) and SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]).

Structural data


Computing details top

Data collection: APEX3 (Bruker, 2016); cell refinement: SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: DIAMOND (Brandenburg & Putz, 2012); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

3-Acetyl-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one top
Crystal data top
C11H10N2O2Z = 2
Mr = 202.21F(000) = 212
Triclinic, P1Dx = 1.442 Mg m3
a = 3.7716 (6) ÅMo Kα radiation, λ = 0.71073 Å
b = 10.3959 (15) ÅCell parameters from 3681 reflections
c = 12.3280 (18) Åθ = 2.4–29.2°
α = 78.017 (2)°µ = 0.10 mm1
β = 83.431 (2)°T = 100 K
γ = 81.266 (2)°Block, colourless
V = 465.63 (12) Å30.21 × 0.20 × 0.11 mm
Data collection top
Bruker SMART APEX CCD
diffractometer
2470 independent reflections
Radiation source: fine-focus sealed tube1901 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.027
Detector resolution: 8.3333 pixels mm-1θmax = 29.3°, θmin = 1.7°
φ and ω scansh = 55
Absorption correction: multi-scan
(SADABS; Bruker, 2016)
k = 1414
Tmin = 0.88, Tmax = 0.99l = 1616
9022 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.049Hydrogen site location: difference Fourier map
wR(F2) = 0.136All H-atom parameters refined
S = 1.00 w = 1/[σ2(Fo2) + (0.0998P)2]
where P = (Fo2 + 2Fc2)/3
2470 reflections(Δ/σ)max < 0.001
176 parametersΔρmax = 0.49 e Å3
0 restraintsΔρmin = 0.23 e Å3
Special details top

Experimental. The diffraction data were obtained from 3 sets of 400 frames, each of width 0.5° in ω, colllected at φ = 0.00, 90.00 and 180.00° and 2 sets of 800 frames, each of width 0.45° in φ, collected at ω = –30.00 and 210.00°. The scan time was 25 sec/frame.

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 > 2sigma(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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.2926 (2)0.34971 (8)0.07890 (6)0.0208 (2)
O20.5557 (2)0.00837 (8)0.28674 (7)0.0249 (2)
N10.2518 (2)0.47066 (9)0.21721 (7)0.0139 (2)
N20.4884 (3)0.37592 (9)0.39182 (7)0.0152 (2)
C10.3175 (3)0.47757 (10)0.32396 (8)0.0142 (2)
C20.1954 (3)0.59856 (11)0.36119 (9)0.0182 (3)
H20.252 (4)0.5959 (14)0.4387 (12)0.024 (3)*
C30.0194 (3)0.70330 (12)0.29381 (9)0.0207 (3)
H30.064 (4)0.7835 (15)0.3192 (13)0.033 (4)*
C40.0399 (3)0.69249 (12)0.18479 (9)0.0196 (3)
H40.161 (4)0.7630 (15)0.1353 (12)0.028 (4)*
C50.0787 (3)0.57829 (11)0.14802 (9)0.0172 (3)
H50.039 (4)0.5650 (14)0.0762 (13)0.031 (4)*
C60.3588 (3)0.34940 (10)0.17422 (8)0.0147 (2)
C70.5185 (3)0.24174 (10)0.25242 (8)0.0140 (2)
C80.5827 (3)0.25987 (11)0.35758 (8)0.0144 (2)
C90.6088 (3)0.10916 (11)0.21968 (9)0.0174 (3)
C100.7731 (4)0.10147 (12)0.10354 (10)0.0222 (3)
H10A0.912 (4)0.1737 (16)0.0714 (13)0.036 (4)*
H10B0.933 (5)0.0147 (18)0.1094 (14)0.048 (5)*
H10C0.586 (5)0.1028 (16)0.0571 (13)0.039 (4)*
C110.7671 (3)0.15253 (11)0.44132 (9)0.0177 (3)
H11A0.592 (4)0.1061 (14)0.4931 (12)0.029 (4)*
H11B0.899 (4)0.1935 (14)0.4844 (12)0.026 (4)*
H11C0.940 (4)0.0891 (14)0.4056 (11)0.028 (4)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0308 (5)0.0203 (4)0.0126 (4)0.0014 (3)0.0067 (3)0.0046 (3)
O20.0339 (5)0.0155 (4)0.0239 (4)0.0019 (4)0.0002 (4)0.0030 (3)
N10.0176 (5)0.0136 (5)0.0107 (4)0.0011 (4)0.0036 (3)0.0020 (3)
N20.0189 (5)0.0137 (5)0.0127 (4)0.0002 (4)0.0033 (3)0.0022 (3)
C10.0157 (6)0.0169 (5)0.0102 (5)0.0019 (4)0.0024 (4)0.0027 (4)
C20.0228 (6)0.0164 (5)0.0155 (5)0.0007 (4)0.0042 (4)0.0046 (4)
C30.0258 (7)0.0177 (6)0.0183 (6)0.0015 (5)0.0026 (5)0.0054 (4)
C40.0222 (6)0.0161 (5)0.0183 (5)0.0016 (4)0.0053 (4)0.0003 (4)
C50.0202 (6)0.0182 (6)0.0125 (5)0.0014 (4)0.0046 (4)0.0006 (4)
C60.0172 (6)0.0150 (5)0.0125 (5)0.0025 (4)0.0021 (4)0.0035 (4)
C70.0160 (6)0.0140 (5)0.0120 (5)0.0012 (4)0.0015 (4)0.0025 (4)
C80.0146 (5)0.0163 (5)0.0118 (5)0.0020 (4)0.0006 (4)0.0020 (4)
C90.0180 (6)0.0172 (5)0.0176 (5)0.0004 (4)0.0036 (4)0.0051 (4)
C100.0268 (7)0.0218 (6)0.0189 (6)0.0020 (5)0.0007 (5)0.0086 (4)
C110.0199 (6)0.0171 (5)0.0148 (5)0.0012 (4)0.0038 (4)0.0012 (4)
Geometric parameters (Å, º) top
O1—C61.2283 (13)C4—H40.947 (16)
O2—C91.2197 (14)C5—H50.955 (15)
N1—C51.3838 (14)C6—C71.4229 (15)
N1—C11.3849 (13)C7—C81.4007 (14)
N1—C61.4515 (13)C7—C91.4952 (14)
N2—C11.3346 (14)C8—C111.4984 (15)
N2—C81.3443 (13)C9—C101.5066 (16)
C1—C21.4214 (14)C10—H10A0.972 (16)
C2—C31.3593 (16)C10—H10B1.001 (18)
C2—H20.997 (14)C10—H10C0.955 (18)
C3—C41.4171 (16)C11—H11A0.974 (15)
C3—H30.948 (15)C11—H11B0.964 (15)
C4—C51.3530 (15)C11—H11C0.990 (14)
C5—N1—C1121.40 (9)C8—C7—C6120.56 (9)
C5—N1—C6117.53 (8)C8—C7—C9121.33 (10)
C1—N1—C6121.07 (9)C6—C7—C9118.11 (9)
C1—N2—C8118.71 (9)N2—C8—C7122.90 (10)
N2—C1—N1122.63 (9)N2—C8—C11113.96 (9)
N2—C1—C2119.61 (9)C7—C8—C11123.13 (9)
N1—C1—C2117.76 (9)O2—C9—C7120.39 (9)
C3—C2—C1120.72 (10)O2—C9—C10120.45 (10)
C3—C2—H2126.2 (8)C7—C9—C10119.15 (10)
C1—C2—H2113.1 (8)C9—C10—H10A112.7 (9)
C2—C3—C4119.75 (10)C9—C10—H10B106.3 (10)
C2—C3—H3120.5 (9)H10A—C10—H10B109.8 (14)
C4—C3—H3119.8 (9)C9—C10—H10C109.1 (9)
C5—C4—C3120.04 (10)H10A—C10—H10C109.2 (13)
C5—C4—H4117.5 (9)H10B—C10—H10C109.6 (14)
C3—C4—H4122.4 (9)C8—C11—H11A110.8 (9)
C4—C5—N1120.31 (10)C8—C11—H11B108.1 (9)
C4—C5—H5123.4 (9)H11A—C11—H11B107.0 (12)
N1—C5—H5116.3 (9)C8—C11—H11C112.1 (8)
O1—C6—C7128.13 (10)H11A—C11—H11C110.6 (12)
O1—C6—N1117.88 (9)H11B—C11—H11C108.0 (12)
C7—C6—N1113.94 (9)
C8—N2—C1—N13.80 (17)C1—N1—C6—C72.35 (15)
C8—N2—C1—C2176.08 (9)O1—C6—C7—C8178.50 (11)
C5—N1—C1—N2179.02 (10)N1—C6—C7—C84.19 (16)
C6—N1—C1—N21.65 (17)O1—C6—C7—C92.57 (18)
C5—N1—C1—C21.10 (16)N1—C6—C7—C9174.74 (9)
C6—N1—C1—C2178.24 (9)C1—N2—C8—C71.82 (17)
N2—C1—C2—C3179.70 (11)C1—N2—C8—C11179.04 (9)
N1—C1—C2—C30.18 (17)C6—C7—C8—N22.34 (17)
C1—C2—C3—C40.70 (19)C9—C7—C8—N2176.56 (9)
C2—C3—C4—C50.05 (19)C6—C7—C8—C11176.72 (10)
C3—C4—C5—N11.32 (18)C9—C7—C8—C114.39 (17)
C1—N1—C5—C41.87 (17)C8—C7—C9—O239.27 (16)
C6—N1—C5—C4177.49 (10)C6—C7—C9—O2139.66 (11)
C5—N1—C6—O10.60 (16)C8—C7—C9—C10139.53 (12)
C1—N1—C6—O1179.95 (10)C6—C7—C9—C1041.55 (15)
C5—N1—C6—C7177.01 (9)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C2—H2···N2i0.997 (14)2.494 (14)3.4679 (15)165.5 (11)
C5—H5···O1ii0.955 (15)2.349 (16)3.1710 (14)143.9 (12)
C10—H10A···O1iii0.972 (16)2.513 (17)3.4153 (16)154.5 (12)
Symmetry codes: (i) x+1, y+1, z+1; (ii) x, y+1, z; (iii) x+1, y, z.
 

Acknowledgements

JTM thanks Tulane University for support of the Tulane Crystallography Laboratory.

References

First citationAwouters, F., Vermeire, J., Smeyers, F., Vermote, P., van Beek, R. & Niemegeers, C. J. E. (1986). Drug Dev. Res. 8, 95–102.  CrossRef CAS Web of Science Google Scholar
First citationBrandenburg, K. & Putz, H. (2012). DIAMOND. Crystal Impact GbR, Bonn, Germany.  Google Scholar
First citationBruker (2016). APEX3, SADABS and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationHarriman, G. C. B., Chi, S., Zhang, M., Crowe, A., Bennett, R. A. & Parsons, I. (2003). Tetrahedron Lett. 44, 3659–3662.  CrossRef CAS Google Scholar
First citationKennis, L. E. J., Bischoff, F. P., Mertens, C. J., Love, C. J., Van den Keybus, F. A. F., Pieters, S., Braeken, M., Megens, A. A. H. P. & Leysen, J. E. (2000). Bioorg. Med. Chem. Lett. 10, 71–74.  CrossRef PubMed CAS Google Scholar
First citationLahmidi, S., El Ouasif, L., Jilalat, A. E., Al-Garadi, W., Essassi, E. M. & Mague, J. T. (2016). IUCrData, 1, x161978.  Google Scholar
First citationMane, U. R., Mohanakrishnan, D., Sahal, D., Murumkar, P. R., Giridhar, R. & Yadav, M. R. (2014). Eur. J. Med. Chem. 79, 422–435.  Web of Science CrossRef CAS PubMed Google Scholar
First citationNargund, L. V. G., Reddy, Y. S. R. & Jose, R. (1991). Indian Drugs, 29, 45–46.  CAS Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015a). Acta Cryst. A71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015b). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationSmith, R. L., Barrett, R. J. & Sanders-Bush, E. J. (1995). J. Pharmacol. Exp. Ther. 275, 1050–1057.  CAS PubMed Google Scholar

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