N-(4-Acetyl-3-methyl-1-phenyl-1H-pyrazol-5-yl)-N-methyl-2-(2-methyl-4-oxo-3,4-dihydroquinazolin-3-yl)benzamide

Fiorella Meneghetti; Benedetta Maggio

doi:10.1107/S1600536813025683

. 2013 Sep 25;69(Pt 10):o1582. doi: 10.1107/S1600536813025683

N-(4-Acetyl-3-methyl-1-phenyl-1H-pyrazol-5-yl)-N-methyl-2-(2-methyl-4-oxo-3,4-dihydroquinazolin-3-yl)benzamide

Fiorella Meneghetti ^a,^*, Benedetta Maggio ^b

PMCID: PMC3790439 PMID: 24098258

Abstract

In the title compound, C₂₉H₂₅N₅O₃, the dihedral angle between the benzene ring and the pendant quinazoline ring system (r.m.s. deviation = 0.036Å) is 87.60 (17)°. The equivalent angle between the pyrazole ring and the phenyl group is 70.0 (2)°. The dihedral angle between the benzene and pyrazole rings is 30.7 (2)° and overall, the molecular conformation approximates to a Z shape. A short intramolecular C—H⋯O contact occurs. In the crystal, the molecules are linked by Cπ—H⋯O-type hydrogen bonds and aromatic π–π stacking interactions [centroid–centroid distance = 3.860 (3) Å], generating a three-dimensional network.

Related literature

For background to the bioactivity of methaqualone and its derivatives, see: Ionescu-Pioggia et al. (1988) ▶; Wolfe et al. (1990 ▶). For structural and molecular modeling studies of quinazolinone derivatives, see: Duke & Codding (1993 ▶). For further synthetic details, see: Plescia et al. (1978 ▶).

Experimental

Crystal data

C₂₉H₂₅N₅O₃
M _r = 491.54
Monoclinic,
a = 8.617 (4) Å
b = 20.438 (5) Å
c = 15.038 (5) Å
β = 106.27 (2)°
V = 2542.3 (16) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 293 K
0.6 × 0.5 × 0.4 mm

Data collection

Enraf–Nonius TurboCAD-4 diffractometer
5236 measured reflections
4401 independent reflections
1358 reflections with I > 2σ(I)
R _int = 0.062
3 standard reflections every 120 min intensity decay: −3%

Refinement

R[F ² > 2σ(F ²)] = 0.047
wR(F ²) = 0.120
S = 0.92
4401 reflections
338 parameters
H-atom parameters constrained
Δρ_max = 0.16 e Å⁻³
Δρ_min = −0.16 e Å⁻³

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994 ▶); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995 ▶); program(s) used to solve structure: SIR92 (Altomare et al., 1994 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▶); software used to prepare material for publication: WinGX publication routines (Farrugia, 2012 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536813025683/hb7092sup1.cif

e-69-o1582-sup1.cif^{(30.9KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813025683/hb7092Isup2.hkl

e-69-o1582-Isup2.hkl^{(211.3KB, hkl)}

Click here for additional data file.^{(9.7KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813025683/hb7092Isup3.cml

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C21—H21C⋯O1	0.96	2.57	3.214 (5)	124
C3—H3⋯O2ⁱ	0.93	2.54	3.351 (6)	146
C5—H5⋯O1ⁱⁱ	0.93	2.40	3.276 (5)	157
C16—H16⋯O3ⁱⁱⁱ	0.93	2.52	3.305 (6)	143

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

Financial support from the Fondo di Finanziamento della Ricerca - ex 60%, University of Palermo, is gratefully acknowledged.

supplementary crystallographic information

1. Comment

The product obtained from 2-acetamido-N-methyl-N-(3-methyl-5-phenyl-1H-pyrazol-5-yl)benzamide by the Bischler–Napieralski reaction (Plescia et al., 1978) was hydrolized by 6 N aqueous hydrochloric acid to give the metaqualone derivative 1, whose definitive structure is now reported (Fig. 1 and 2). The compound C29 H25 N5 O3 crystallizes in the monoclinic P2₁/c space group. The overall molecular conformation has about a Z shape (Fig. 2). The presence of an intramolecular hydrogen bond between C2—H2···O1 at a distance of 2.65 (1) Å, angle 129 (1)° contributes to stabilize the folded conformation of the molecule. The 2-methyl-4-oxoquinazolin-3(4H)-yl)benzamide moiety is characterized by an almost planar conformation, with the maximum deviation out of its best mean plane for O2 and C21 atoms by 0.103 (4) Å and -0.198 (5) Å, respectively. The bicyclic system is nearly perpendicularly oriented with respect to the N4-attached phenyl ring (dihedral angle 87.60 (17)°), while it forms with the distal ones a dihedral angle of 41.0 (1)°. The pyrazole is inclined of 70.0 (2)° with respect to both the bicyclic moiety and the C1—C6 benzene, while it presents a dihedral angle of 30.7 (2)° with the C12—C17 phenyl ring. The two benzene are oriented each other at 51.6 (2)°. The molecular packing is stabilized by intermolecular interactions type Cπ—H···O between: C3—H3···O2i of 2.51 (3) Å and 146 (1)° [symmetry code: (i) x + 1, y, z], C5—H5···O1ii contact of 2.40 (3) Å and 157 (1)° [symmetry code: (ii) x, 1/2 - y, z - 1/2], and C16—H16···O3iii at distance of 2.51 (4) Å, angle 143 (1)° [symmetry code: (iii) 2 - x, y + 1/2, 1/2 - z] (Fig. 3). Stacking interactions between the benzene o f the oxoquinazoline systems [centroid-centroid distance = 3.860 (3) Å] further consolidate the packing.

2. Experimental

A solution of the product obtained from 2-acetamido-N-methyl-N-(3-methyl-5-phenyl-1H-pyrazol-5-yl)benzamide by the Bischler-Napieralski reaction (Plescia et al., 1978) (6 g.) in 60 ml of aqueous 6 N hydrochloric acid was refluxed for 25 minutes. The precipitated solid (3.2 g) was crystallized from ethanol-diethyl ether to give a product which was dissolved in chloroform (100 ml) and treated with triethylamine (5 ml). The solution was stirred for 1 h at room temperature, washed with water (3 × 100 ml) and dried (sodium sulfate). Removal of the solvent and the crystallization from ethanol of the residue afforded to the title compound.