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

Lahmidi, S.; Abad, N.; Boulhaoua, M.; Sebbar, N.K.; Essassi, E.M.; Mague, J.T.

doi:10.1107/S2414314617009919

organic compounds

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ISSN: 2414-3146

Volume 2| Part 7| July 2017| x170991

https://doi.org/10.1107/S2414314617009919

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

Sanae Lahmidi,^a ^* Nadeem Abad,^a Mohammed Boulhaoua,^a Nada Kheira Sebbar,^a El Mokhtar Essassi ^a and Joel T. Mague ^b

^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 π–π stacking interactions and C—H⋯O hydrogen bonds. The stacks are associated in centrosymmetric pairs through C—H⋯N hydrogen bonds.

Keywords: crystal structure; hydrogen bonding; pyridopyrimidine; π–π stacking.

CCDC reference: 1560036

Structure description

Pyrido[1,2-a]pyrimidine derivatives exhibit a broad range of biological activities (Harriman et al., 2003 ), including antibacterial (Nargund et al., 1991 ) and antimalarial agents (Mane et al., 2014 ). Also, the antiallergic agent ramastine (Awouters et al., 1986 ), the antidepressant lusaperidone (Kennis et al., 2000 ) and the tranquilizer pirenperone (Smith et al., 1995 ) derive from such aza-bridgehead-fused heterocyclic compounds. As part of our ongoing studies (Lahmidi et al., 2016 ) 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). 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 π–π 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 and Fig. 2). 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 and Fig. 2).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	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
The molecular structure of the title compound, with displacement ellipsoids drawn at the 50% probability level.

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 π–π 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.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₁H₁₀N₂O₂
M_r	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)
V (Å³)	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 )
T_min, T_max	0.88, 0.99
No. of measured, independent and observed [I > 2σ(I)] reflections	9022, 2470, 1901
R_int	0.027
(sin θ/λ)_max (Å⁻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
Δρ_max, Δρ_min (e Å⁻³)	0.49, −0.23
Computer programs: APEX3 and SAINT (Bruker, 2016), SHELXT (Sheldrick, 2015a ), SHELXL2014 (Sheldrick, 2015b ), DIAMOND (Brandenburg & Putz, 2012 ) and SHELXTL (Sheldrick, 2008 ).

Structural data

CCDC reference: 1560036

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S2414314617009919/wm4051sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314617009919/wm4051Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314617009919/wm4051Isup3.cdx

Supporting information file. DOI: https://doi.org/10.1107/S2414314617009919/wm4051Isup4.cml

checkCIF report

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

C₁₁H₁₀N₂O₂	Z = 2
M_r = 202.21	F(000) = 212
Triclinic, P1	D_x = 1.442 Mg m⁻³
a = 3.7716 (6) Å	Mo Kα radiation, λ = 0.71073 Å
b = 10.3959 (15) Å	Cell parameters from 3681 reflections
c = 12.3280 (18) Å	θ = 2.4–29.2°
α = 78.017 (2)°	µ = 0.10 mm⁻¹
β = 83.431 (2)°	T = 100 K
γ = 81.266 (2)°	Block, colourless
V = 465.63 (12) Å³	0.21 × 0.20 × 0.11 mm

Data collection top

Bruker SMART APEX CCD diffractometer	2470 independent reflections
Radiation source: fine-focus sealed tube	1901 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.027
Detector resolution: 8.3333 pixels mm^-1	θ_max = 29.3°, θ_min = 1.7°
φ and ω scans	h = −5→5
Absorption correction: multi-scan (SADABS; Bruker, 2016)	k = −14→14
T_min = 0.88, T_max = 0.99	l = −16→16
9022 measured reflections

Refinement top

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: difference Fourier map
wR(F²) = 0.136	All H-atom parameters refined
S = 1.00	w = 1/[σ²(F_o²) + (0.0998P)²] where P = (F_o² + 2F_c²)/3
2470 reflections	(Δ/σ)_max < 0.001
176 parameters	Δρ_max = 0.49 e Å⁻³
0 restraints	Δρ_min = −0.23 e Å⁻³

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

	x	y	z	U_iso*/U_eq
O1	0.2926 (2)	0.34971 (8)	0.07890 (6)	0.0208 (2)
O2	0.5557 (2)	0.00837 (8)	0.28674 (7)	0.0249 (2)
N1	0.2518 (2)	0.47066 (9)	0.21721 (7)	0.0139 (2)
N2	0.4884 (3)	0.37592 (9)	0.39182 (7)	0.0152 (2)
C1	0.3175 (3)	0.47757 (10)	0.32396 (8)	0.0142 (2)
C2	0.1954 (3)	0.59856 (11)	0.36119 (9)	0.0182 (3)
H2	0.252 (4)	0.5959 (14)	0.4387 (12)	0.024 (3)*
C3	0.0194 (3)	0.70330 (12)	0.29381 (9)	0.0207 (3)
H3	−0.064 (4)	0.7835 (15)	0.3192 (13)	0.033 (4)*
C4	−0.0399 (3)	0.69249 (12)	0.18479 (9)	0.0196 (3)
H4	−0.161 (4)	0.7630 (15)	0.1353 (12)	0.028 (4)*
C5	0.0787 (3)	0.57829 (11)	0.14802 (9)	0.0172 (3)
H5	0.039 (4)	0.5650 (14)	0.0762 (13)	0.031 (4)*
C6	0.3588 (3)	0.34940 (10)	0.17422 (8)	0.0147 (2)
C7	0.5185 (3)	0.24174 (10)	0.25242 (8)	0.0140 (2)
C8	0.5827 (3)	0.25987 (11)	0.35758 (8)	0.0144 (2)
C9	0.6088 (3)	0.10916 (11)	0.21968 (9)	0.0174 (3)
C10	0.7731 (4)	0.10147 (12)	0.10354 (10)	0.0222 (3)
H10A	0.912 (4)	0.1737 (16)	0.0714 (13)	0.036 (4)*
H10B	0.933 (5)	0.0147 (18)	0.1094 (14)	0.048 (5)*
H10C	0.586 (5)	0.1028 (16)	0.0571 (13)	0.039 (4)*
C11	0.7671 (3)	0.15253 (11)	0.44132 (9)	0.0177 (3)
H11A	0.592 (4)	0.1061 (14)	0.4931 (12)	0.029 (4)*
H11B	0.899 (4)	0.1935 (14)	0.4844 (12)	0.026 (4)*
H11C	0.940 (4)	0.0891 (14)	0.4056 (11)	0.028 (4)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0308 (5)	0.0203 (4)	0.0126 (4)	−0.0014 (3)	−0.0067 (3)	−0.0046 (3)
O2	0.0339 (5)	0.0155 (4)	0.0239 (4)	−0.0019 (4)	0.0002 (4)	−0.0030 (3)
N1	0.0176 (5)	0.0136 (5)	0.0107 (4)	−0.0011 (4)	−0.0036 (3)	−0.0020 (3)
N2	0.0189 (5)	0.0137 (5)	0.0127 (4)	−0.0002 (4)	−0.0033 (3)	−0.0022 (3)
C1	0.0157 (6)	0.0169 (5)	0.0102 (5)	−0.0019 (4)	−0.0024 (4)	−0.0027 (4)
C2	0.0228 (6)	0.0164 (5)	0.0155 (5)	0.0007 (4)	−0.0042 (4)	−0.0046 (4)
C3	0.0258 (7)	0.0177 (6)	0.0183 (6)	0.0015 (5)	−0.0026 (5)	−0.0054 (4)
C4	0.0222 (6)	0.0161 (5)	0.0183 (5)	0.0016 (4)	−0.0053 (4)	0.0003 (4)
C5	0.0202 (6)	0.0182 (6)	0.0125 (5)	−0.0014 (4)	−0.0046 (4)	−0.0006 (4)
C6	0.0172 (6)	0.0150 (5)	0.0125 (5)	−0.0025 (4)	−0.0021 (4)	−0.0035 (4)
C7	0.0160 (6)	0.0140 (5)	0.0120 (5)	−0.0012 (4)	−0.0015 (4)	−0.0025 (4)
C8	0.0146 (5)	0.0163 (5)	0.0118 (5)	−0.0020 (4)	−0.0006 (4)	−0.0020 (4)
C9	0.0180 (6)	0.0172 (5)	0.0176 (5)	−0.0004 (4)	−0.0036 (4)	−0.0051 (4)
C10	0.0268 (7)	0.0218 (6)	0.0189 (6)	−0.0020 (5)	0.0007 (5)	−0.0086 (4)
C11	0.0199 (6)	0.0171 (5)	0.0148 (5)	0.0012 (4)	−0.0038 (4)	−0.0012 (4)

Geometric parameters (Å, º) top

O1—C6	1.2283 (13)	C4—H4	0.947 (16)
O2—C9	1.2197 (14)	C5—H5	0.955 (15)
N1—C5	1.3838 (14)	C6—C7	1.4229 (15)
N1—C1	1.3849 (13)	C7—C8	1.4007 (14)
N1—C6	1.4515 (13)	C7—C9	1.4952 (14)
N2—C1	1.3346 (14)	C8—C11	1.4984 (15)
N2—C8	1.3443 (13)	C9—C10	1.5066 (16)
C1—C2	1.4214 (14)	C10—H10A	0.972 (16)
C2—C3	1.3593 (16)	C10—H10B	1.001 (18)
C2—H2	0.997 (14)	C10—H10C	0.955 (18)
C3—C4	1.4171 (16)	C11—H11A	0.974 (15)
C3—H3	0.948 (15)	C11—H11B	0.964 (15)
C4—C5	1.3530 (15)	C11—H11C	0.990 (14)

C5—N1—C1	121.40 (9)	C8—C7—C6	120.56 (9)
C5—N1—C6	117.53 (8)	C8—C7—C9	121.33 (10)
C1—N1—C6	121.07 (9)	C6—C7—C9	118.11 (9)
C1—N2—C8	118.71 (9)	N2—C8—C7	122.90 (10)
N2—C1—N1	122.63 (9)	N2—C8—C11	113.96 (9)
N2—C1—C2	119.61 (9)	C7—C8—C11	123.13 (9)
N1—C1—C2	117.76 (9)	O2—C9—C7	120.39 (9)
C3—C2—C1	120.72 (10)	O2—C9—C10	120.45 (10)
C3—C2—H2	126.2 (8)	C7—C9—C10	119.15 (10)
C1—C2—H2	113.1 (8)	C9—C10—H10A	112.7 (9)
C2—C3—C4	119.75 (10)	C9—C10—H10B	106.3 (10)
C2—C3—H3	120.5 (9)	H10A—C10—H10B	109.8 (14)
C4—C3—H3	119.8 (9)	C9—C10—H10C	109.1 (9)
C5—C4—C3	120.04 (10)	H10A—C10—H10C	109.2 (13)
C5—C4—H4	117.5 (9)	H10B—C10—H10C	109.6 (14)
C3—C4—H4	122.4 (9)	C8—C11—H11A	110.8 (9)
C4—C5—N1	120.31 (10)	C8—C11—H11B	108.1 (9)
C4—C5—H5	123.4 (9)	H11A—C11—H11B	107.0 (12)
N1—C5—H5	116.3 (9)	C8—C11—H11C	112.1 (8)
O1—C6—C7	128.13 (10)	H11A—C11—H11C	110.6 (12)
O1—C6—N1	117.88 (9)	H11B—C11—H11C	108.0 (12)
C7—C6—N1	113.94 (9)

C8—N2—C1—N1	−3.80 (17)	C1—N1—C6—C7	2.35 (15)
C8—N2—C1—C2	176.08 (9)	O1—C6—C7—C8	178.50 (11)
C5—N1—C1—N2	−179.02 (10)	N1—C6—C7—C8	−4.19 (16)
C6—N1—C1—N2	1.65 (17)	O1—C6—C7—C9	−2.57 (18)
C5—N1—C1—C2	1.10 (16)	N1—C6—C7—C9	174.74 (9)
C6—N1—C1—C2	−178.24 (9)	C1—N2—C8—C7	1.82 (17)
N2—C1—C2—C3	−179.70 (11)	C1—N2—C8—C11	−179.04 (9)
N1—C1—C2—C3	0.18 (17)	C6—C7—C8—N2	2.34 (17)
C1—C2—C3—C4	−0.70 (19)	C9—C7—C8—N2	−176.56 (9)
C2—C3—C4—C5	−0.05 (19)	C6—C7—C8—C11	−176.72 (10)
C3—C4—C5—N1	1.32 (18)	C9—C7—C8—C11	4.39 (17)
C1—N1—C5—C4	−1.87 (17)	C8—C7—C9—O2	39.27 (16)
C6—N1—C5—C4	177.49 (10)	C6—C7—C9—O2	−139.66 (11)
C5—N1—C6—O1	0.60 (16)	C8—C7—C9—C10	−139.53 (12)
C1—N1—C6—O1	179.95 (10)	C6—C7—C9—C10	41.55 (15)
C5—N1—C6—C7	−177.01 (9)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	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.

Acknowledgements

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

References

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

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

Structure description

Synthesis and crystallization

Refinement

Structural data

Acknowledgements

References

organic compounds