1,5-Dimethyl-3-[(3-phenyl-4,5-dihydro-1,2-oxazol-5-yl)meth­yl]-1H-1,5-benzodiazepine-2,4(3H,5H)-dione

Dardouri, R.; Kandri Rodi, Y.; Saffon, N.; El Ammari, L.; Essassi, E.M.

doi:10.1107/S1600536810042972

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 66| Part 11| November 2010| Page o2983

https://doi.org/10.1107/S1600536810042972

Open

access

1,5-Dimethyl-3-[(3-phenyl-4,5-dihydro-1,2-oxazol-5-yl)methyl]-1H-1,5-benzodiazepine-2,4(3H,5H)-dione

Rachida Dardouri,^a Youssef Kandri Rodi,^a Nathalie Saffon,^b Lahcen El Ammari ^c and El Mokhtar Essassi ^d ^*

^aLaboratoire de Chimie Organique Appliquée, Faculté des Sciences et Techniques, Université Sidi Mohamed Ben Abdallah, Fés, Morocco, ^bService Commun Rayons-X FR2599, Université Paul Sabatier, Bâtiment 2R1, 118 route de Narbonne, Toulouse, France, ^cLaboratoire de Chimie du Solide Appliquée, Faculté des Sciences, Université Mohammed V-Agdal, Avenue Ibn Battouta, BP 1014, Rabat, Morocco, and ^dINANOTECH (Institute of Nanomaterials and Nanotechnology), Mascir, avenue de l'Armée Royale, Rabat, Morocco
^*Correspondence e-mail: emessassi@yahoo.fr

(Received 12 October 2010; accepted 21 October 2010; online 30 October 2010)

The reaction of 3-allyl-1,5-dimethyl-1,5-benzodiazepine-2,4-dione and benzaldoxime leads to the title compound, C₂₁H₂₁N₃O₃. The molecular structure is built up from two fused six- and seven-membered rings linked to a chain including a five- and six-membered ring (isoxazoline and phenyl) via a methylene group. The seven-membered ring displays a boat conformation. The dihedral angle between the two six-membered rings is 74.3 (1)°.

Related literature

For the biological activity and pharmaceutical properties of benzodiazepines and their derivatives, see: Cherif Alaoui, et al. (2007 ); Fruscella et al. (2001 ); Guerrini et al. (2006 ); Jabli et al., (2009 ); Keita et al. (2003 ); Rajarao et al. (2007 ); Kalkhambkar et al. (2008 ); Poisbeau et al. (1997 ); Smith et al. (1998 ); Kotyatkina et al. (2001 ). For their reactivity, see: Kosychova et al. (2004 ); Nabih et al. (2003 ); Reddy et al. (2000 ).

Experimental

Crystal data

C₂₁H₂₁N₃O₃
M_r = 363.41
Monoclinic, P 2₁ /n
a = 9.3491 (2) Å
b = 6.9722 (1) Å
c = 27.9201 (5) Å
β = 93.157 (1)°
V = 1817.18 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 296 K
0.40 × 0.38 × 0.36 mm

Data collection

Bruker SMART CCD area-detector diffractometer
28704 measured reflections
3717 independent reflections
3261 reflections with I > 2σ(I)
R_int = 0.031

Refinement

R[F² > 2σ(F²)] = 0.057
wR(F²) = 0.148
S = 1.04
3717 reflections
246 parameters
H-atom parameters constrained
Δρ_max = 0.49 e Å⁻³
Δρ_min = −0.34 e Å⁻³

Data collection: SMART (Bruker, 2001 ); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia,1997 ); software used to prepare material for publication: WinGX (Farrugia, 1999 ).

Supporting information

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S1600536810042972/im2239sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536810042972/im2239Isup2.hkl

checkCIF report

Comment top

Benzodiazepines and their derivatives have attracted considerable attention from researchers due to their bioactive and pharmaceutical properties. Many members of this family are widely used as anticonvulsant, anti-anxiety, anti-seizures, analgesic, seditative, antidepressive and hypnotic or anti-inflammatory agents (Rajarao et al., 2007; Guerrini et al., 2006; Kotyatkina et al., 2001; Fruscella et al., 2001). They have also been used as antibacterial and antifungal agents (Kalkhambkar et al., 2008; Smith et al.,1998) and in the management of skeletomuscular spasticity, panic or as premedication prior to surgery (Poisbeau et al., 1997). In addition, 1,5-benzodiazepines have found applications as readily available intermediates in the synthesis of fused ring compounds such as triazolo-, oxazolo-, isoxazolo-, oxazino- or furano-benzodiazepine (Kosychova et al., 2004; Nabih et al., 2003; Reddy et al., 2000). Benzodiazepine derivatives also find commercial use as dyes for acrylic fibers.

The search for new heterocyclic systems including the 1,5-benzodiazepine-2,4-dione moiety for biological activities therefore is of much current importance (Keita et al. 2003; Cherif Alaoui et al., 2007; Jabli et al., 2009).

In this work we were mainly interested in the reactivity of the exocyclic C=C bond of the allyl substituent towards nitriloxides. The latter are produced as intermediates from the dehydrohalogenation of benzaldoxime by a solution of sodium hypochlorite. The oxime then reacts with 3-allyl-1,5-dimethyl-1,5-benzodiazepine-2,4-dione in a biphasic medium (water-chloroform) at 0°C during 4 h to lead a unique cycloadduct 1,5-dimethyl-3-(3-phenyl-4,5-dihydro-isoxazol-5-ylmethyl)- 1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione, in good yields (Scheme 1).

The molecular structure of 1,5-dimethyl-3-(3-phenyl-4,5-dihydro-isoxazol-5-ylmethyl)-1,5-dihydro- benzo[b][1,4]diazepine-2,4-dione is built up from two fused six-and seven-membered rings linked to a side-chain of a five and a six-membered ring via a methylene group (Fig.1). The isoxazoline and phenyl rings are almost coplanar with a dihedral angle between them of 2.67 (7)°. In the fused rings, the aromatic six-membered ring has a perfect planar conformation, whereas the seven-membered ring displays a boat conformation with total puckering amplitude QT = 0.999 (2) Å and spherical polar angles of θ = 76.63 (2)°, φ2 = -1.12 (1)° and φ3 = 0.83 (5)°. The torsion angles C9–C1–C12–C13 and C1–C12–C13–C14 are 72.20 (2)° and 177.20 (2)° respectively.

Related literature top

For the biological activity and pharmaceutical properties of benzodiazepines and their derivatives, see: Cherif Alaoui, et al. (2007); Fruscella et al. (2001); Guerrini et al. (2006); Jabli et al., (2009); Keita et al. (2003); Rajarao et al. (2007); Kalkhambkar et al. (2008); Poisbeau et al. (1997); Smith et al. (1998); Kotyatkina et al. (2001). For their reactivity, see: Kosychova et al. (2004); Nabih et al. (2003); Reddy et al. (2000).

Experimental top

To a solution of 3-allyl-1,5-dimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione (0.5 g, 2 mmol) and benzaldoxime (0.3 g, 2.5 mmol) in chloroform (16 ml) was added dropwise a 24% sodium hypochlorite solution (8 ml) at 0°C. Stirring was continued for 4 h. The organic layer was dried over Na₂SO₄ and the solvent was evaporated under reduced pressure. The residue was then purified by column chromatography on silica gel using a mixture of hexane/ethyl acetate (v/v = 1/1) as eluent. Colorless crystals were isolated when the solvent was allowed to evaporate (yield: 75%).

Structure description top

For the biological activity and pharmaceutical properties of benzodiazepines and their derivatives, see: Cherif Alaoui, et al. (2007); Fruscella et al. (2001); Guerrini et al. (2006); Jabli et al., (2009); Keita et al. (2003); Rajarao et al. (2007); Kalkhambkar et al. (2008); Poisbeau et al. (1997); Smith et al. (1998); Kotyatkina et al. (2001). For their reactivity, see: Kosychova et al. (2004); Nabih et al. (2003); Reddy et al. (2000).

Computing details top

Data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT (Bruker, 2001); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia,1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top

Fig. 1. Molecular structure of the title compound with the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are represented as small circles.

1,5-Dimethyl-3-[(3-phenyl-4,5-dihydro-1,2-oxazol-5-yl)methyl]- 1H-1,5-benzodiazepine-2,4(3H,5H)-dione top

Crystal data top

C₂₁H₂₁N₃O₃	F(000) = 768
M_r = 363.41	D_x = 1.328 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 9929 reflections
a = 9.3491 (2) Å	θ = 2.9–30.5°
b = 6.9722 (1) Å	µ = 0.09 mm⁻¹
c = 27.9201 (5) Å	T = 296 K
β = 93.157 (1)°	Block, colourless
V = 1817.18 (6) Å³	0.40 × 0.38 × 0.36 mm
Z = 4

Data collection top

Bruker SMART CCD area-detector diffractometer	3261 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.031
Graphite monochromator	θ_max = 26.4°, θ_min = 1.5°
phi and ω scans	h = −11→11
28704 measured reflections	k = −8→8
3717 independent reflections	l = −34→34

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)] = 0.057	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.148	H-atom parameters constrained
S = 1.04	w = 1/[σ²(F_o²) + (0.057P)² + 1.9064P] where P = (F_o² + 2F_c²)/3
3717 reflections	(Δ/σ)_max < 0.001
246 parameters	Δρ_max = 0.49 e Å⁻³
0 restraints	Δρ_min = −0.34 e Å⁻³

Crystal data top

C₂₁H₂₁N₃O₃	V = 1817.18 (6) Å³
M_r = 363.41	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 9.3491 (2) Å	µ = 0.09 mm⁻¹
b = 6.9722 (1) Å	T = 296 K
c = 27.9201 (5) Å	0.40 × 0.38 × 0.36 mm
β = 93.157 (1)°

Data collection top

Bruker SMART CCD area-detector diffractometer	3261 reflections with I > 2σ(I)
28704 measured reflections	R_int = 0.031
3717 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.057	0 restraints
wR(F²) = 0.148	H-atom parameters constrained
S = 1.04	Δρ_max = 0.49 e Å⁻³
3717 reflections	Δρ_min = −0.34 e Å⁻³
246 parameters

Special details top

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.

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.

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

	x	y	z	U_iso*/U_eq
O1	0.30152 (16)	0.5636 (3)	0.20375 (6)	0.0494 (4)
O2	0.22075 (18)	0.1345 (3)	0.12654 (6)	0.0491 (4)
O3	0.07230 (18)	0.6193 (3)	0.04335 (7)	0.0613 (6)
N1	0.07203 (18)	0.5003 (2)	0.22029 (6)	0.0325 (4)
N2	0.00716 (18)	0.1746 (2)	0.15947 (6)	0.0318 (4)
N3	0.1055 (2)	0.7758 (4)	0.01417 (8)	0.0563 (6)
C1	0.1419 (2)	0.4598 (3)	0.13807 (7)	0.0330 (4)
H1	0.0487	0.5157	0.1282	0.040*
C2	0.1802 (2)	0.5157 (3)	0.18989 (8)	0.0342 (5)
C3	−0.0714 (2)	0.4552 (3)	0.20444 (7)	0.0273 (4)
C4	−0.1840 (2)	0.5679 (3)	0.21943 (7)	0.0346 (5)
H4	−0.1645	0.6706	0.2400	0.042*
C5	−0.3242 (2)	0.5290 (3)	0.20406 (8)	0.0389 (5)
H5	−0.3982	0.6047	0.2145	0.047*
C6	−0.3540 (2)	0.3778 (3)	0.17330 (8)	0.0382 (5)
H6	−0.4480	0.3533	0.1624	0.046*
C7	−0.2445 (2)	0.2627 (3)	0.15860 (7)	0.0336 (4)
H7	−0.2655	0.1603	0.1381	0.040*
C8	−0.1026 (2)	0.2986 (3)	0.17428 (7)	0.0268 (4)
C9	0.1275 (2)	0.2418 (3)	0.13959 (7)	0.0334 (5)
C10	0.1040 (3)	0.5479 (4)	0.27119 (8)	0.0460 (6)
H10A	0.1908	0.4848	0.2824	0.069*
H10B	0.0266	0.5058	0.2898	0.069*
H10C	0.1155	0.6842	0.2746	0.069*
C11	−0.0081 (3)	−0.0331 (3)	0.16577 (10)	0.0479 (6)
H11A	0.0173	−0.0977	0.1371	0.072*
H11B	−0.1055	−0.0626	0.1721	0.072*
H11C	0.0540	−0.0749	0.1923	0.072*
C12	0.2525 (2)	0.5268 (4)	0.10382 (8)	0.0395 (5)
H12A	0.2736	0.6613	0.1097	0.047*
H12B	0.3404	0.4548	0.1099	0.047*
C13	0.2009 (2)	0.5008 (4)	0.05218 (8)	0.0435 (5)
H13	0.1786	0.3656	0.0457	0.052*
C14	0.3060 (3)	0.5754 (4)	0.01653 (8)	0.0454 (6)
H14A	0.3993	0.6017	0.0321	0.054*
H14B	0.3167	0.4856	−0.0096	0.054*
C15	0.2327 (2)	0.7564 (4)	−0.00061 (8)	0.0400 (5)
C16	0.2942 (2)	0.8996 (3)	−0.03233 (7)	0.0357 (5)
C17	0.2153 (2)	1.0624 (4)	−0.04645 (8)	0.0416 (5)
H17	0.1246	1.0817	−0.0352	0.050*
C18	0.2715 (2)	1.1944 (4)	−0.07698 (9)	0.0455 (6)
H18	0.2183	1.3021	−0.0863	0.055*
C19	0.4069 (2)	1.1680 (4)	−0.09397 (8)	0.0441 (5)
H19	0.4438	1.2569	−0.1148	0.053*
C20	0.4862 (2)	1.0094 (4)	−0.07983 (8)	0.0417 (5)
H20	0.5775	0.9920	−0.0908	0.050*
C21	0.4301 (2)	0.8760 (3)	−0.04936 (7)	0.0376 (5)
H21	0.4840	0.7689	−0.0401	0.045*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0309 (8)	0.0572 (11)	0.0589 (10)	−0.0073 (7)	−0.0071 (7)	−0.0018 (8)
O2	0.0468 (9)	0.0525 (10)	0.0488 (9)	0.0202 (8)	0.0092 (7)	−0.0012 (8)
O3	0.0354 (9)	0.0933 (15)	0.0558 (11)	0.0041 (9)	0.0070 (8)	0.0310 (10)
N1	0.0323 (8)	0.0317 (9)	0.0329 (9)	−0.0016 (7)	−0.0043 (7)	−0.0033 (7)
N2	0.0353 (9)	0.0258 (8)	0.0341 (9)	0.0033 (7)	−0.0004 (7)	−0.0021 (7)
N3	0.0358 (10)	0.0837 (17)	0.0502 (12)	0.0095 (10)	0.0098 (9)	0.0248 (12)
C1	0.0240 (9)	0.0394 (11)	0.0355 (10)	0.0023 (8)	0.0023 (8)	0.0057 (9)
C2	0.0301 (10)	0.0288 (10)	0.0433 (11)	0.0006 (8)	−0.0030 (8)	0.0018 (9)
C3	0.0294 (9)	0.0271 (9)	0.0254 (9)	−0.0012 (7)	0.0005 (7)	0.0043 (7)
C4	0.0411 (11)	0.0323 (10)	0.0311 (10)	0.0037 (9)	0.0073 (8)	0.0007 (8)
C5	0.0343 (10)	0.0454 (13)	0.0381 (11)	0.0097 (9)	0.0108 (8)	0.0105 (10)
C6	0.0268 (9)	0.0501 (13)	0.0378 (11)	−0.0031 (9)	0.0016 (8)	0.0137 (10)
C7	0.0334 (10)	0.0360 (11)	0.0309 (10)	−0.0064 (8)	−0.0022 (8)	0.0032 (8)
C8	0.0282 (9)	0.0262 (9)	0.0261 (9)	0.0003 (7)	0.0021 (7)	0.0046 (7)
C9	0.0316 (10)	0.0406 (11)	0.0279 (10)	0.0093 (9)	−0.0007 (8)	−0.0003 (8)
C10	0.0476 (13)	0.0508 (14)	0.0381 (12)	0.0017 (11)	−0.0096 (10)	−0.0118 (10)
C11	0.0525 (14)	0.0262 (11)	0.0638 (15)	0.0033 (10)	−0.0079 (12)	−0.0012 (10)
C12	0.0295 (10)	0.0477 (13)	0.0416 (12)	−0.0011 (9)	0.0047 (9)	0.0052 (10)
C13	0.0413 (12)	0.0481 (13)	0.0417 (12)	0.0002 (10)	0.0078 (10)	0.0031 (10)
C14	0.0461 (13)	0.0521 (14)	0.0388 (12)	0.0057 (11)	0.0102 (10)	0.0026 (11)
C15	0.0359 (11)	0.0525 (14)	0.0317 (10)	0.0034 (10)	0.0014 (8)	0.0006 (10)
C16	0.0353 (10)	0.0452 (12)	0.0263 (9)	0.0037 (9)	0.0004 (8)	−0.0029 (9)
C17	0.0331 (10)	0.0492 (13)	0.0426 (12)	0.0057 (10)	0.0037 (9)	−0.0041 (10)
C18	0.0430 (12)	0.0409 (13)	0.0513 (14)	0.0042 (10)	−0.0086 (10)	0.0000 (11)
C19	0.0430 (12)	0.0484 (13)	0.0404 (12)	−0.0126 (10)	−0.0015 (9)	0.0013 (10)
C20	0.0296 (10)	0.0586 (14)	0.0371 (11)	−0.0018 (10)	0.0037 (8)	−0.0073 (10)
C21	0.0347 (10)	0.0458 (12)	0.0322 (10)	0.0068 (9)	−0.0001 (8)	−0.0033 (9)

Geometric parameters (Å, º) top

O1—C2	1.225 (2)	C10—H10B	0.9600
O2—C9	1.220 (2)	C10—H10C	0.9600
O3—N3	1.407 (3)	C11—H11A	0.9600
O3—C13	1.469 (3)	C11—H11B	0.9600
N1—C2	1.360 (3)	C11—H11C	0.9600
N1—C3	1.424 (2)	C12—C13	1.506 (3)
N1—C10	1.474 (3)	C12—H12A	0.9700
N2—C9	1.364 (3)	C12—H12B	0.9700
N2—C8	1.420 (2)	C13—C14	1.527 (3)
N2—C11	1.467 (3)	C13—H13	0.9800
N3—C15	1.287 (3)	C14—C15	1.502 (3)
C1—C12	1.520 (3)	C14—H14A	0.9700
C1—C2	1.522 (3)	C14—H14B	0.9700
C1—C9	1.527 (3)	C15—C16	1.472 (3)
C1—H1	0.9800	C16—C21	1.391 (3)
C3—C4	1.396 (3)	C16—C17	1.398 (3)
C3—C8	1.400 (3)	C17—C18	1.378 (3)
C4—C5	1.383 (3)	C17—H17	0.9300
C4—H4	0.9300	C18—C19	1.388 (3)
C5—C6	1.378 (3)	C18—H18	0.9300
C5—H5	0.9300	C19—C20	1.377 (3)
C6—C7	1.381 (3)	C19—H19	0.9300
C6—H6	0.9300	C20—C21	1.383 (3)
C7—C8	1.397 (3)	C20—H20	0.9300
C7—H7	0.9300	C21—H21	0.9300
C10—H10A	0.9600

N3—O3—C13	109.19 (16)	N2—C11—H11B	109.5
C2—N1—C3	122.92 (17)	H11A—C11—H11B	109.5
C2—N1—C10	117.75 (17)	N2—C11—H11C	109.5
C3—N1—C10	119.14 (17)	H11A—C11—H11C	109.5
C9—N2—C8	122.31 (17)	H11B—C11—H11C	109.5
C9—N2—C11	118.38 (18)	C13—C12—C1	111.85 (18)
C8—N2—C11	119.31 (18)	C13—C12—H12A	109.2
C15—N3—O3	109.9 (2)	C1—C12—H12A	109.2
C12—C1—C2	112.76 (17)	C13—C12—H12B	109.2
C12—C1—C9	112.80 (18)	C1—C12—H12B	109.2
C2—C1—C9	104.18 (16)	H12A—C12—H12B	107.9
C12—C1—H1	109.0	O3—C13—C12	108.00 (19)
C2—C1—H1	109.0	O3—C13—C14	104.44 (19)
C9—C1—H1	109.0	C12—C13—C14	113.5 (2)
O1—C2—N1	122.1 (2)	O3—C13—H13	110.2
O1—C2—C1	122.36 (19)	C12—C13—H13	110.2
N1—C2—C1	115.42 (17)	C14—C13—H13	110.2
C4—C3—C8	118.96 (18)	C15—C14—C13	101.25 (18)
C4—C3—N1	119.68 (18)	C15—C14—H14A	111.5
C8—C3—N1	121.35 (17)	C13—C14—H14A	111.5
C5—C4—C3	120.9 (2)	C15—C14—H14B	111.5
C5—C4—H4	119.6	C13—C14—H14B	111.5
C3—C4—H4	119.6	H14A—C14—H14B	109.3
C6—C5—C4	119.9 (2)	N3—C15—C16	121.3 (2)
C6—C5—H5	120.0	N3—C15—C14	113.6 (2)
C4—C5—H5	120.0	C16—C15—C14	125.12 (19)
C5—C6—C7	120.13 (19)	C21—C16—C17	118.5 (2)
C5—C6—H6	119.9	C21—C16—C15	121.3 (2)
C7—C6—H6	119.9	C17—C16—C15	120.20 (19)
C6—C7—C8	120.6 (2)	C18—C17—C16	120.2 (2)
C6—C7—H7	119.7	C18—C17—H17	119.9
C8—C7—H7	119.7	C16—C17—H17	119.9
C7—C8—C3	119.40 (18)	C17—C18—C19	120.6 (2)
C7—C8—N2	119.25 (18)	C17—C18—H18	119.7
C3—C8—N2	121.35 (17)	C19—C18—H18	119.7
O2—C9—N2	122.0 (2)	C20—C19—C18	119.7 (2)
O2—C9—C1	122.5 (2)	C20—C19—H19	120.1
N2—C9—C1	115.40 (17)	C18—C19—H19	120.1
N1—C10—H10A	109.5	C19—C20—C21	120.0 (2)
N1—C10—H10B	109.5	C19—C20—H20	120.0
H10A—C10—H10B	109.5	C21—C20—H20	120.0
N1—C10—H10C	109.5	C20—C21—C16	121.0 (2)
H10A—C10—H10C	109.5	C20—C21—H21	119.5
H10B—C10—H10C	109.5	C16—C21—H21	119.5
N2—C11—H11A	109.5

Experimental details

Crystal data
Chemical formula	C₂₁H₂₁N₃O₃
M_r	363.41
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	296
a, b, c (Å)	9.3491 (2), 6.9722 (1), 27.9201 (5)
β (°)	93.157 (1)
V (Å³)	1817.18 (6)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.40 × 0.38 × 0.36

Data collection
Diffractometer	Bruker SMART CCD area-detector
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	28704, 3717, 3261
R_int	0.031
(sin θ/λ)_max (Å⁻¹)	0.625

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.057, 0.148, 1.04
No. of reflections	3717
No. of parameters	246
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.49, −0.34

Computer programs: SMART (Bruker, 2001), SAINT (Bruker, 2001), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia,1997), WinGX (Farrugia, 1999).

References

Bruker (2001). SAINT and SMART. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Cherif Alaoui, L., Kandri Rodi, Y., Haoudi, A., Obbade, S. & Essassi, E. M. (2007). Acta Cryst. E63, o3494. Web of Science CSD CrossRef IUCr Journals Google Scholar
Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565. CrossRef IUCr Journals Google Scholar
Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838. CrossRef CAS IUCr Journals Google Scholar
Fruscella, P., Sottocorno, M., Braccio, M. D., Diomede, L., Piccardi, N., Cagnotto, A., Grossi, G., Romano, M., Mennini, T. & Roma, G. (2001). Pharmacol. Res. 43, 445–452. Web of Science CrossRef PubMed CAS Google Scholar
Guerrini, G., Costanzo, A., Ciciani, G., Bruni, F., Selleri, S., Costagli, C., Besnard, F., Costa, B., Martini, C., Siena, G. D. & Malmberg-Aiello, P. (2006). Bioorg. Med. Chem. 14, 758–775. Web of Science CrossRef PubMed CAS Google Scholar
Jabli, H., Kandri Rodi, Y., Saffon, N., Essassi, E. M. & Ng, S. W. (2009). Acta Cryst. E65, o3150. Web of Science CSD CrossRef IUCr Journals Google Scholar
Kalkhambkar, R. G., Kulkarni, G. M., Kamanavalli, C. M., Premkumar, N., Asdaq, S. M. & Sun, C. M. (2008). Eur. J. Med. Chem. 43, 2178–2188. Web of Science CrossRef PubMed CAS Google Scholar
Keita, A., Lazrak, F., Essassi, E. M., Cherif Alaoui, I., Kandri Rodi, Y., Bellan, J. & Pierrot, M. (2003). Phosphorus Sulfur Silicon Relat. Elem. 178, 1541–1548. Web of Science CrossRef CAS Google Scholar
Kosychova, L., Stumbreviciute, Z., Pleckaitiene, L., Janciene, R. & Puodziunaite, B. D. (2004). Chem. Heterocycl. Compd, 40, 811–815. CrossRef CAS Google Scholar
Kotyatkina, A. I., Zhabinsky, V. N. & Khripach Russ, V. A. (2001). Chem. Rev. 70, 641–653. CAS Google Scholar
Nabih, K., Baouid, A., Hasnaoui, A., Selkti, M. & Compain, P. (2003). New J. Chem. 27, 1644–1648. Web of Science CSD CrossRef CAS Google Scholar
Poisbeau, P., Williams, S. R. & Mody, I. (1997). J. Neurosci. 17, 3467–3475. CAS PubMed Web of Science Google Scholar
Rajarao, S. J., Platt, B., Sukoff, S. J., Lin, Q., Bender, C. N., Nieuwenhuijsen, B. W., Ring, R. H., Schechter, L. E., Rosenzweig-Lipson, S. & Beyer, C. E. (2007). Neuropeptides, 41, 307–320. Web of Science CrossRef PubMed CAS Google Scholar
Reddy, K. V. V., Rao, P. S. & Ashok, D. (2000). Synth. Commun. 30, 1825–1836. Web of Science CrossRef CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Smith, R. H., Jorgen, W. L., Tirado, R. J. & Lamb, M. L. (1998). J. Med. Chem. 41, 5272–5286. CrossRef CAS PubMed Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.