3-(2,6-Dioxopiperidin-3-yl)-3-aza­bicyclo­[3.2.0]heptane-2,4-dione

Hijji, Y.M.; Benjamin, E.; Benjamin, E.; Butcher, R.J.; Jasinski, J.P.

doi:10.1107/S1600536809002839

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 65| Part 2| February 2009| Pages o394-o395

doi:10.1107/S1600536809002839

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3-(2,6-Dioxopiperidin-3-yl)-3-azabicyclo[3.2.0]heptane-2,4-dione

Yousef M. Hijji,^a Ellis Benjamin,^b Earl Benjamin,^b Ray J. Butcher ^c ^* and Jerry P. Jasinski ^d

^aDepartment of Chemistry, Morgan State University, Baltimore, MD 21251, USA, ^bDepartment of Chemistry and Physics, Arkansas State University, PO Box 419, State University, AR 72467, USA, ^cDepartment of Chemistry, Howard University, 525 College Street NW, Washington, DC 20059, USA, and ^dDepartment of Chemistry, Keene State College, 229 Main Street, Keene, NH 03435-2001, USA
^*Correspondence e-mail: rbutcher99@yahoo.com

(Received 1 December 2008; accepted 22 January 2009; online 28 January 2009)

The title molecule, C₁₁H₁₂N₂O₄, consists of a 3-azabicyclo[3.2.0]heptane group containing a nearly planar cyclobutane ring (r.m.s. deviation of fitted atoms is 0.0609 Å), fused to a pyrrolidine ring, bonded to a 2,6-dioxopiperidine ring at the 3-position. The angle between the mean planes of the cyclobutane and fused pyrrolidine ring is 67.6 (6)°. The dihedral angles between the mean planes of the pyrrolidine and cyclobutane rings and the dioxopiperidine ring are 73.9 (2) and 62.4 (4)°, respectively. The pyrrolidine and dioxopiperidine rings are twisted about the 3-yl group [torsion angles = −55.0 (1) and 115.0 (1)°] in a nearly perpendicular manner. Crystal packing is influenced by extensive intermolecular C—H⋯O and N—H⋯O interactions between all four carbonyl O atoms and H atoms from the cyclobutane and dioxopiperidine rings, as well as between the N atom and an H atom from the cyclobutane ring. In addition, weak π-ring interactions also occur between H atoms from the cyclobutane ring and the five-membered pyrrolidine ring. As a result, molecules are linked into infinite chains diagonally along the [101] plane of the unit cell in an alternate inverted pattern.

Related literature

For related structures, see: Muller & Man (2008 ); Yamamoto et al. (2008 ); Zeldis (2008 ). For related literature, see: Carson et al. (2004 ); Werbel et al. (1968 ); Cremer & Pople (1975 ); Schmidt & Polik (2007 ).

Experimental

Crystal data

C₁₁H₁₂N₂O₄
M_r = 236.23
Monoclinic, P 2₁ /a
a = 10.7332 (7) Å
b = 9.9358 (5) Å
c = 11.0753 (7) Å
β = 116.201 (8)°
V = 1059.75 (13) Å³
Z = 4
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 200 (2) K
0.57 × 0.34 × 0.19 mm

Data collection

Oxford Diffraction Gemini diffractometer
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2007 $[Oxford Diffraction (2007). CrysAlis Pro and CrysAlis RED. Oxford Diffraction Ltd, Abingdon, Oxfordshire, England.]$ ) T_min = 0.866, T_max = 0.975
10798 measured reflections
3496 independent reflections
2193 reflections with I > 2σ(I)
R_int = 0.025

Refinement

R[F² > 2σ(F²)] = 0.039
wR(F²) = 0.108
S = 0.99
3496 reflections
154 parameters
H-atom parameters constrained
Δρ_max = 0.28 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2B⋯O3ⁱ	0.88	2.06	2.9426 (12)	175
C5—H5A⋯O4ⁱⁱ	1.00	2.52	3.4424 (15)	153
C10—H10B⋯O2ⁱⁱⁱ	0.99	2.56	3.4228 (14)	146
C11—H11B⋯O3ⁱⁱ	0.99	2.53	3.5026 (13)	167
C11—H11B⋯O1ⁱⁱ	0.99	2.53	3.1072 (14)	117
C3—H3A⋯O4^iv	0.99	2.52	3.2577 (15)	131
Symmetry codes: (i) -x, -y, -z+1; (ii) $[-x+{\script{1\over 2}}, y+{\script{1\over 2}}, -z+1]$ ; (iii) -x, -y+1, -z+1; (iv) x, y, z-1.

Data collection: CrysAlisPro (Oxford Diffraction, 2007 $[Oxford Diffraction (2007). CrysAlis Pro and CrysAlis RED. Oxford Diffraction Ltd, Abingdon, Oxfordshire, England.]$ ); cell refinement: CrysAlisPro; data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809002839/cs2103sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809002839/cs2103Isup2.hkl

checkCIF report

Comment top

The synthesis and biological evaluation of the title compound, 3-(2,6-dioxopiperidine-3-yl)-3-azabicyclo[3.2.0]heptane-2,4-dione and its analogues is of interest to synthetic medicinal chemists. Specifically, piperidine 2,6-dione derivatives, including those of phthalimide, are important anti-angiogenic and immunomodulative agents used for the treatment of many diseases including multiple myeloma, (Muller & Man, 2008; Yamamoto et al., 2008; Zeldis, 2008), Chron's disease (Carson et al., 2004), and leprosy (Werbel et al., 1968). The title molecule, C₁₁H₁₂N₂O₄, a piperidine 2,6-dione derivative, consists of an azabicyclo[3.2.0]heptane group containing a nearly planar cyclobutane ring, fused to a pyrrolidine ring, bonded to a 2,6-dioxopiperidine ring at the 3 position. The six-membered dioxopiperidine ring (N2–C8–C7–C11–C10–C9) is a slightly distorted envelope, with Cremer & Pople (1975) puckering parameters Q, θ and ϕ of 0.5187 (12) Å, 56.12 (13)° and 176.55 (16)°, respectively. The 5-membered pyrrolidine group (N1/C2–C6) has also a slightly distorted envelope conformation with puckering parameters Q(2)and ϕ(2) of 0.0940 (13) Å, 82.9 (7)° respectively. For an ideal envelope θ has a value of 0 or 180° and θ(2) has a value of 72. The angle between the mean planes of the cyclobutane and fused pyrrolidine ring is 67.6 (6)° (Fig. 1). The mean planes of the pyrrolidine and cyclobutane rings make an angle of 73.9 (2)° and 62.4 (4)° with the dihedral angle of the dioxopiperidine ring, respectively. The pyrrolidine and dioxopiperidine rings are twisted about the 3-yl group [torsion angles = -55.0 (1)° (C1—N1—C7—C8) and 115.0 (1)° (C6—N1—C7—C8)] in a nearly perpendicular manner.

Crystal packing is influenced by extensive intermolecular C–H···O hydrogen bonding between all four carbonyl oxygen atoms [O1, O2, O3, O4] and hydrogen atoms from the cyclobutane (H3A & H5A) and dioxopiperidine rings (H10B & H11B) as well as by N–H···O intermolecular interactions. As a result the molecules are linked into infinite chains diagonally along the [101] plane of the unit cell in an alternate inverted pattern (Fig. 2). In addition, weak C-H··· π-ring interactions also occur between hydrogen atoms from the cyclobutane ring [H3B] and the 5-membered pyrrolidine ring [C3–H3B···Cg2; H3B···Cg2 = 2.50 Å, C3–H3B···Cg2 = 64°, C3···Cg2–H3B = 2.2475 (13) Å, x,y,z, where Cg2 = center of gravity of the N1/C1/C2/C5/C6 ring].

After a MOPAC AMI calculation [Austin Model 1 approximation together with the Hartree-Fock closed-shell (restricted) wavefunction was used and minimizations were terminnated at an r.m.s. gradient of less than 0.01 kJ mol^-1 Å^-1] with WebMO Pro (Schmidt & Polik, 2007), the mean planes of the cyclopropane and pyrrolidine rings became completely planar in the local minimized structure and the dihedral angle between these rings became 64.3 (8)°. The angle between the mean planes of the pyrrolidine and cyclobutane rings and the dihedral angle of the dioxopiperidine ring became 73.9 (2)° and 62.4 (4)°, respectively. The twist of the pyrrolidine and dioxopiperidine rings about the 3-yl group became more perpendicuar to each other after this geometry minimization [torsion angles = -68.6 (6)° (C1—N1—C7—C8) and 100.4 (1)° (C6—N1—C7—C8)]. Thus it is apparent that the extensive hydrogen bonding and π-ring intermolecular interactions significantly influence crystal packing for this molecule.

Related literature top

For related structures, see: Muller et al. (2008); Yamamoto et al. (2008); Zeldis et al. (2008). For related literature, see: Carson et al. (2004); Werbel et al. (1968); Cremer & Pople (1975); Schmidt & Polik (2007).

Experimental top

The title compound was synthesized as follows: cis-1,2-cyclobutane dicarboxylic acid anhydride (0.1 g, 0.79 mmol), glutamic acid (0.12 g, 0.79 mmol), DMAP (0.02 g, 0.16 mmol), and ammonium chloride (NH₄Cl) (0.04 g, 0.916 mmol) were mixed thoroughly in a CEM-sealed vial with a magnetic stirrer. The mixture was heated for 10 min at 423 K in a CEM Discover microwave powered at 150 W. It was then cooled rapidly to 313 K and dissolved in 15 ml of (1:1) ethyl acetate: acetone. The organic layer was washed with 2x (10 ml) distilled water and dried over sodium sulfate (anhydrous). The organic layer was concentrated under vacuum and precipitated with hexanes (30 ml) affording a white solid, recrystallized from methanol, (0.10 g, 54%). mp 476–478 K; ¹H NMR (400 MHz, DMSO-d₆), δ (p.p.m.): 11.06 (s, 1 H, NH), 4.95 (dd, 1 H, 12.5, 5.5 Hz), 2.84 (m, 2 H), 2.52 (m, 4 H,), 2.02 (m, 2 H), 1.92 (m, 2 H); ¹³C NMR (100 MHz, DMSO-d₆) δ (p.p.m.): 179.0(C=O), 172.7(C=O), 169.4(C=O), 49.1(CH), 37.9(CH), 37.7(CH), 30.7(CH), 22.3(CH₂), 22.0(CH₂), 21.0(CH₂); MS m/z 236 (M+) 208, 151, 106, 112, 96, 83, 55, 41; IR (nujol) (ν_max, cm^-1): 3207.48, 1702.55, 1729.09, 1771.79 (C=O).

Computing details top

Data collection: CrysAlis PRO (Oxford Diffraction, 2007); cell refinement: CrysAlis PRO (Oxford Diffraction, 2007); data reduction: CrysAlis RED (Oxford Diffraction, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top

	Fig. 1. The molecular structure of C₁₁H₁₂N₂O₄, showing the atom numbering scheme and 50% probability displacement ellipsoids.
	Fig. 2. The molecular packing for C₁₁H₁₂N₂O₄ viewed down the b axis. Dashed lines indicate C–H···O and N–H···O intermolecular hydrogen bonds.

3-(2,6-Dioxopiperidin-3-yl)-3-azabicyclo[3.2.0]heptane-2,4-dione top

Crystal data top

C₁₁H₁₂N₂O₄	F(000) = 496
M_r = 236.23	D_x = 1.481 Mg m⁻³
Monoclinic, P2₁/a	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yab	Cell parameters from 4629 reflections
a = 10.7332 (7) Å	θ = 4.9–32.6°
b = 9.9358 (5) Å	µ = 0.11 mm⁻¹
c = 11.0753 (7) Å	T = 200 K
β = 116.201 (8)°	Prism, colorless
V = 1059.75 (13) Å³	0.57 × 0.34 × 0.19 mm
Z = 4

Data collection top

Oxford Diffraction Gemini diffractometer	3496 independent reflections
Radiation source: fine-focus sealed tube	2193 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.025
Detector resolution: 10.5081 pixels mm^-1	θ_max = 32.5°, θ_min = 4.9°
ϕ and ω scans	h = −14→16
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2007)	k = −14→13
T_min = 0.866, T_max = 0.975	l = −15→15
10798 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)] = 0.039	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.108	H-atom parameters constrained
S = 0.99	w = 1/[σ²(F_o²) + (0.0607P)²] where P = (F_o² + 2F_c²)/3
3496 reflections	(Δ/σ)_max < 0.001
154 parameters	Δρ_max = 0.28 e Å⁻³
0 restraints	Δρ_min = −0.25 e Å⁻³

Crystal data top

C₁₁H₁₂N₂O₄	V = 1059.75 (13) Å³
M_r = 236.23	Z = 4
Monoclinic, P2₁/a	Mo Kα radiation
a = 10.7332 (7) Å	µ = 0.11 mm⁻¹
b = 9.9358 (5) Å	T = 200 K
c = 11.0753 (7) Å	0.57 × 0.34 × 0.19 mm
β = 116.201 (8)°

Data collection top

Oxford Diffraction Gemini diffractometer	3496 independent reflections
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2007)	2193 reflections with I > 2σ(I)
T_min = 0.866, T_max = 0.975	R_int = 0.025
10798 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.039	0 restraints
wR(F²) = 0.108	H-atom parameters constrained
S = 0.99	Δρ_max = 0.28 e Å⁻³
3496 reflections	Δρ_min = −0.25 e Å⁻³
154 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.

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

	x	y	z	U_iso*/U_eq
O1	0.32277 (8)	0.13630 (8)	0.42230 (7)	0.0271 (2)
O2	0.04309 (9)	0.50429 (9)	0.26752 (8)	0.0372 (2)
O3	0.02024 (7)	0.12103 (8)	0.39189 (7)	0.02458 (19)
O4	0.16813 (8)	0.16581 (9)	0.83857 (8)	0.0350 (2)
N1	0.18201 (8)	0.32243 (9)	0.37104 (8)	0.0196 (2)
N2	0.10433 (9)	0.14479 (9)	0.61681 (8)	0.0222 (2)
H2B	0.0683	0.0660	0.6195	0.027*
C1	0.25634 (10)	0.22276 (11)	0.34235 (10)	0.0211 (2)
C2	0.23146 (11)	0.24120 (12)	0.19918 (11)	0.0258 (3)
H2A	0.3154	0.2315	0.1827	0.031*
C3	0.09860 (12)	0.16602 (13)	0.09668 (11)	0.0340 (3)
H3A	0.1154	0.1076	0.0330	0.041*
H3B	0.0487	0.1164	0.1396	0.041*
C4	0.03228 (13)	0.30239 (14)	0.03642 (11)	0.0357 (3)
H4A	−0.0594	0.3172	0.0355	0.043*
H4B	0.0281	0.3205	−0.0532	0.043*
C5	0.15349 (12)	0.37539 (12)	0.15340 (11)	0.0278 (3)
H5A	0.2019	0.4464	0.1259	0.033*
C6	0.11702 (11)	0.41346 (11)	0.26561 (10)	0.0240 (2)
C7	0.15765 (10)	0.31947 (11)	0.49000 (10)	0.0190 (2)
H7A	0.0905	0.3931	0.4805	0.023*
C8	0.08854 (9)	0.18701 (11)	0.49330 (10)	0.0188 (2)
C9	0.17118 (10)	0.21274 (12)	0.73885 (10)	0.0234 (2)
C10	0.24295 (11)	0.34041 (11)	0.73556 (10)	0.0249 (2)
H10A	0.3260	0.3520	0.8228	0.030*
H10B	0.1799	0.4172	0.7239	0.030*
C11	0.28713 (10)	0.34228 (11)	0.62276 (10)	0.0220 (2)
H11A	0.3561	0.2704	0.6369	0.026*
H11B	0.3300	0.4300	0.6209	0.026*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0272 (4)	0.0236 (4)	0.0302 (4)	0.0056 (3)	0.0125 (3)	0.0028 (3)
O2	0.0488 (5)	0.0302 (5)	0.0331 (4)	0.0158 (4)	0.0185 (4)	0.0085 (4)
O3	0.0235 (4)	0.0233 (4)	0.0256 (4)	−0.0044 (3)	0.0096 (3)	−0.0028 (3)
O4	0.0448 (5)	0.0383 (5)	0.0276 (4)	−0.0018 (4)	0.0211 (4)	0.0041 (4)
N1	0.0226 (4)	0.0176 (5)	0.0209 (4)	0.0009 (3)	0.0117 (3)	0.0022 (4)
N2	0.0252 (4)	0.0186 (5)	0.0252 (4)	−0.0048 (3)	0.0134 (4)	0.0012 (4)
C1	0.0196 (5)	0.0198 (5)	0.0263 (5)	−0.0028 (4)	0.0124 (4)	−0.0009 (4)
C2	0.0295 (6)	0.0251 (6)	0.0279 (5)	−0.0016 (4)	0.0174 (5)	−0.0016 (5)
C3	0.0441 (7)	0.0330 (7)	0.0254 (6)	−0.0064 (5)	0.0158 (5)	−0.0041 (5)
C4	0.0385 (7)	0.0436 (8)	0.0218 (5)	0.0015 (6)	0.0103 (5)	0.0005 (5)
C5	0.0347 (6)	0.0256 (6)	0.0255 (5)	−0.0027 (5)	0.0155 (5)	0.0034 (5)
C6	0.0265 (5)	0.0203 (6)	0.0238 (5)	−0.0007 (4)	0.0098 (4)	0.0032 (4)
C7	0.0203 (5)	0.0170 (5)	0.0217 (5)	0.0004 (4)	0.0110 (4)	0.0008 (4)
C8	0.0156 (4)	0.0195 (5)	0.0224 (5)	0.0016 (4)	0.0093 (4)	0.0013 (4)
C9	0.0226 (5)	0.0247 (6)	0.0248 (5)	0.0025 (4)	0.0122 (4)	0.0012 (5)
C10	0.0294 (5)	0.0217 (6)	0.0225 (5)	−0.0019 (4)	0.0105 (4)	−0.0023 (4)
C11	0.0215 (5)	0.0193 (5)	0.0248 (5)	−0.0030 (4)	0.0099 (4)	−0.0014 (4)

Geometric parameters (Å, º) top

O1—C1	1.2136 (13)	C3—H3B	0.9900
O2—C6	1.2080 (13)	C4—C5	1.5520 (16)
O3—C8	1.2253 (12)	C4—H4A	0.9900
O4—C9	1.2125 (13)	C4—H4B	0.9900
N1—C1	1.3936 (14)	C5—C6	1.5069 (16)
N1—C6	1.3959 (13)	C5—H5A	1.0000
N1—C7	1.4523 (13)	C7—C8	1.5191 (15)
N2—C8	1.3679 (13)	C7—C11	1.5298 (13)
N2—C9	1.3933 (13)	C7—H7A	1.0000
N2—H2B	0.8800	C9—C10	1.4929 (16)
C1—C2	1.4984 (15)	C10—C11	1.5195 (15)
C2—C5	1.5364 (17)	C10—H10A	0.9900
C2—C3	1.5654 (15)	C10—H10B	0.9900
C2—H2A	1.0000	C11—H11A	0.9900
C3—C4	1.5390 (18)	C11—H11B	0.9900
C3—H3A	0.9900

C1—N1—C6	113.25 (9)	C6—C5—H5A	115.6
C1—N1—C7	122.88 (8)	C2—C5—H5A	115.6
C6—N1—C7	123.25 (9)	C4—C5—H5A	115.6
C8—N2—C9	127.22 (9)	O2—C6—N1	123.98 (10)
C8—N2—H2B	116.4	O2—C6—C5	127.86 (10)
C9—N2—H2B	116.4	N1—C6—C5	108.14 (9)
O1—C1—N1	123.21 (9)	N1—C7—C8	108.95 (8)
O1—C1—C2	129.16 (10)	N1—C7—C11	114.71 (8)
N1—C1—C2	107.57 (9)	C8—C7—C11	110.57 (8)
C1—C2—C5	105.78 (9)	N1—C7—H7A	107.4
C1—C2—C3	112.87 (9)	C8—C7—H7A	107.4
C5—C2—C3	89.18 (8)	C11—C7—H7A	107.4
C1—C2—H2A	115.3	O3—C8—N2	120.82 (10)
C5—C2—H2A	115.3	O3—C8—C7	122.84 (9)
C3—C2—H2A	115.3	N2—C8—C7	116.33 (9)
C4—C3—C2	89.61 (9)	O4—C9—N2	119.20 (10)
C4—C3—H3A	113.7	O4—C9—C10	124.80 (10)
C2—C3—H3A	113.7	N2—C9—C10	116.00 (9)
C4—C3—H3B	113.7	C9—C10—C11	112.47 (9)
C2—C3—H3B	113.7	C9—C10—H10A	109.1
H3A—C3—H3B	111.0	C11—C10—H10A	109.1
C3—C4—C5	89.58 (8)	C9—C10—H10B	109.1
C3—C4—H4A	113.7	C11—C10—H10B	109.1
C5—C4—H4A	113.7	H10A—C10—H10B	107.8
C3—C4—H4B	113.7	C10—C11—C7	107.91 (9)
C5—C4—H4B	113.7	C10—C11—H11A	110.1
H4A—C4—H4B	111.0	C7—C11—H11A	110.1
C6—C5—C2	104.34 (9)	C10—C11—H11B	110.1
C6—C5—C4	112.24 (10)	C7—C11—H11B	110.1
C2—C5—C4	90.21 (9)	H11A—C11—H11B	108.4

C6—N1—C1—O1	178.13 (10)	C2—C5—C6—O2	−171.68 (11)
C7—N1—C1—O1	−10.65 (15)	C4—C5—C6—O2	−75.45 (15)
C6—N1—C1—C2	−4.49 (11)	C2—C5—C6—N1	7.10 (11)
C7—N1—C1—C2	166.72 (9)	C4—C5—C6—N1	103.32 (11)
O1—C1—C2—C5	−174.12 (11)	C1—N1—C7—C8	−55.34 (12)
N1—C1—C2—C5	8.72 (11)	C6—N1—C7—C8	115.01 (10)
O1—C1—C2—C3	89.96 (14)	C1—N1—C7—C11	69.19 (12)
N1—C1—C2—C3	−87.20 (11)	C6—N1—C7—C11	−120.47 (10)
C1—C2—C3—C4	115.83 (10)	C9—N2—C8—O3	−175.72 (9)
C5—C2—C3—C4	9.02 (9)	C9—N2—C8—C7	3.25 (15)
C2—C3—C4—C5	−8.93 (9)	N1—C7—C8—O3	−24.63 (13)
C1—C2—C5—C6	−9.47 (11)	C11—C7—C8—O3	−151.56 (9)
C3—C2—C5—C6	104.11 (9)	N1—C7—C8—N2	156.42 (9)
C1—C2—C5—C4	−122.52 (9)	C11—C7—C8—N2	29.49 (12)
C3—C2—C5—C4	−8.94 (9)	C8—N2—C9—O4	174.97 (10)
C3—C4—C5—C6	−96.51 (11)	C8—N2—C9—C10	−5.28 (15)
C3—C4—C5—C2	9.10 (9)	O4—C9—C10—C11	153.52 (11)
C1—N1—C6—O2	177.01 (10)	N2—C9—C10—C11	−26.21 (13)
C7—N1—C6—O2	5.83 (16)	C9—C10—C11—C7	56.95 (12)
C1—N1—C6—C5	−1.83 (11)	N1—C7—C11—C10	178.27 (9)
C7—N1—C6—C5	−173.01 (9)	C8—C7—C11—C10	−58.05 (11)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2B···O3ⁱ	0.88	2.06	2.9426 (12)	175
C5—H5A···O4ⁱⁱ	1.00	2.52	3.4424 (15)	153
C10—H10B···O2ⁱⁱⁱ	0.99	2.56	3.4228 (14)	146
C11—H11B···O3ⁱⁱ	0.99	2.53	3.5026 (13)	167
C11—H11B···O1ⁱⁱ	0.99	2.53	3.1072 (14)	117
C3—H3A···O4^iv	0.99	2.52	3.2577 (15)	131

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

Experimental details

Crystal data
Chemical formula	C₁₁H₁₂N₂O₄
M_r	236.23
Crystal system, space group	Monoclinic, P2₁/a
Temperature (K)	200
a, b, c (Å)	10.7332 (7), 9.9358 (5), 11.0753 (7)
β (°)	116.201 (8)
V (Å³)	1059.75 (13)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.11
Crystal size (mm)	0.57 × 0.34 × 0.19

Data collection
Diffractometer	Oxford Diffraction Gemini diffractometer
Absorption correction	Multi-scan (CrysAlis RED; Oxford Diffraction, 2007)
T_min, T_max	0.866, 0.975
No. of measured, independent and observed [I > 2σ(I)] reflections	10798, 3496, 2193
R_int	0.025
(sin θ/λ)_max (Å⁻¹)	0.756

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.039, 0.108, 0.99
No. of reflections	3496
No. of parameters	154
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.28, −0.25

Computer programs: CrysAlis PRO (Oxford Diffraction, 2007), CrysAlis RED (Oxford Diffraction, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2B···O3ⁱ	0.88	2.06	2.9426 (12)	174.9
C5—H5A···O4ⁱⁱ	1.00	2.52	3.4424 (15)	152.6
C10—H10B···O2ⁱⁱⁱ	0.99	2.56	3.4228 (14)	145.8
C11—H11B···O3ⁱⁱ	0.99	2.53	3.5026 (13)	166.8
C11—H11B···O1ⁱⁱ	0.99	2.53	3.1072 (14)	116.6
C3—H3A···O4^iv	0.99	2.52	3.2577 (15)	130.9

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

Acknowledgements

RJB acknowledges the NSF MRI program (grant No. CHE-0619278) for funds to purchase an X-ray diffractometer.

References

Carson, K. G., Jaffee, B. D. & Harriman, G. C. B. (2004). Annu. Rep. Med. Chem. 39, 149–158. Web of Science CrossRef CAS Google Scholar
Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358. CrossRef CAS Web of Science Google Scholar
Muller, G. W. & Man, H.-W. (2008). PCT Int. Appl. PIXXD2 WO 2008039489 A2 20080403. Google Scholar
Oxford Diffraction (2007). CrysAlis Pro and CrysAlis RED. Oxford Diffraction Ltd, Abingdon, Oxfordshire, England. Google Scholar
Schmidt, J. R. & Polik, W. F. (2007). WebMO Pro. WebMO, LLC, Holland, Michigan, USA, 2007. http://www.webmo.net Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Werbel, L. M., Elslager, E. F., Fisher, M. W., Gavrilis, Z. B. & Phillips, A. A. (1968). J. Med. Chem. 11, 411–419. CrossRef CAS PubMed Web of Science Google Scholar
Yamamoto, T., Shibata, N., Takashima, M., Nakamura, S., Toru, T., Matsunaga, N. & Hara, H. (2008). Org. Biomol. Chem. 6, 1540–1543. Web of Science CrossRef PubMed CAS Google Scholar
Zeldis, J. B. (2008). PCT Int. Appl. PIXXD2. WO 2008019065, A1 20080214, CAN 148:230111, AN 2008:191687. Google Scholar