Crystal structure of the α-racemate of methohexital

Gelbrich, T.; Griesser, U.J.

doi:10.1107/S205698901500105X

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Volume 71| Part 2| February 2015| Pages 206-209

doi:10.1107/S205698901500105X

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Crystal structure of the α-racemate of methohexital

Thomas Gelbrich ^a ^* and Ulrich J. Griesser ^a

^aInstitute of Pharmacy, University of Innsbruck, Innrain 52c, 6020 Innsbruck, Austria
^*Correspondence e-mail: thomas.gelbrich@uibk.ac.at

Edited by M. Weil, Vienna University of Technology, Austria (Received 15 December 2014; accepted 18 January 2015; online 24 January 2015)

Molecules of the title compound, C₁₄H₁₈N₂O₃ [systematic name: 5-allyl-5-(hex-3-yn-2-yl)-1-methylpyrimidine-2,4,6(1H,3H,5H)-trione in the (R_bS_h)/(S_bR_h) racemic form], are connected by mutual N—H⋯O=C hydrogen bonds in which the carbonyl group at the 2-position of the pyrimidinetrione ring is employed. These interactions result in an inversion dimer which displays a central R₂²(8) ring motif. This dimer is topologically distinct from that of the previously reported (S_bR_h) form, which is, however, also based on an R₂²(8) motif. The methyl group at the 1-position of the pyrimidinetrione ring in the title structure is disordered over two sets of sites in a 0.57 (2):0.43 (2) ratio.

Keywords: crystal structure; barbiturate; hydrogen bonding; anaesthetic.

CCDC reference: 1044166

1. Chemical context

The title compound is a barbiturate derivative, the Na salt of which (trade name Brevimytal, Eli Lilly) is a widely used short-acting anaesthetic with a rapid onset of action. The molecule contains two asymmetric centres and can exist as two diastereomeric enantiomer pairs. Its stereoisomerism is known to affect the anaesthetic activity and possible side effects of the drug (Gibson et al., 1959 ). The crystal structure of the (S_bR_h) form of methohexital was previously reported by Brunner et al. (2003 ), who also established that the commercial product (α-racemate) consists of the (R_bS_h) and (S_bR_h) isomers.

2. Structural commentary

This study confirmed the presence of the (R_bS_h)/(S_bR_h) racemate. The molecule (Fig. 1) displays an approximately planar pyrimidinetrione unit in which the oxygen atoms of the C2 and C4 carbonyl groups lie at distances of −0.160 (2) and 0.156 (2) Å from the mean plane of the six-membered ring (r.m.s. deviation = 0.046 Å). The conformation of the two 5-substituents of the ring is characterized by three parameters, the torsion angles C5—C7—C8—C9 of −103.3 (2) and C10—C5—C7—C8 of −171.51 (13)° and the pseudo-torsion angle C5—C10⋯C13–C14 of 23.2 (2)°.

Figure 1
The molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level; hydrogen atoms are drawn as spheres of arbitrary size.

The previously reported (S_bR_h) form contains two independent molecules (denoted A and B), which differ from the molecule of the title structure in the conformation adopted by the terminal groups of both 5-substituents (Fig. 2). Specifically, in molecule A, the torsion angle analogous to C5—C7—C8—C9 in the present α-racemate is 125.3°, and the pseudo-torsion angles analogous to C5—C10⋯C13—C14 of the title structure are −15.4° (A) and −26.3° (B).

Figure 2
Overlay of the molecule of the α-racemate (denoted X) with the two independent molecules (A, B) of the previously reported (S_bR_h) form, generated by least-squares fits of their 1-methyl-2,4,6-pyrimidinetrione units (ten non-H atomic positions).

3. Supramolecular features

Two molecules are linked to one another by two mutual antiparallel N—H⋯O=C bonds so that an inversion dimer is formed (Table 1, Fig. 3), which displays a central $[R_{2}^{2}]$ (8) ring motif (Etter et al., 1990 ; Bernstein et al., 1995 ). This interaction involves the carbonyl group at the 2-position of the ring. The $[R_{2}^{2}]$ (8) ring motif is also present in the (S_bR_h) form (Brunner et al., 2003) where it connects the two crystallographically independent molecules. However, in this case the dimer is based on two topologically distinct N—H⋯O=C interactions which involve the carbonyl groups at the 4-position of the ring of molecule A and at the 2-position of molecule B.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N3—H3⋯O2ⁱ	0.85 (2)	2.03 (2)	2.8826 (17)	173.2 (17)
Symmetry code: (i) -x, -y, -z+1.

Figure 3
The N—H⋯O=C hydrogen-bonded inversion dimer displaying a central $[R_{2}^{2}]$ (8) ring. These interactions (dotted lines) involve the carbonyl group at the 2-position of the six-membered ring. O and H atoms engaged in hydrogen bonding are drawn as spheres.

4. Database survey

The Cambridge Structural Database (Groom & Allen, 2014 ; Version 3.35) contains 11 unique entries for derivatives of barbituric acid which are analogous to the title compound and substituted at the 1-position, but not at the 3-position of the six-membered ring. A common characteristic of these compounds is the presence of one hydrogen-bond donor group (NH) and three potential acceptor groups, viz. the carbonyl groups at the ring positions 2, 4 and 6. Thus, three topologically distinct hydrogen-bonding acceptor interactions are possible. Additionally, there is a competition between possible dimer and catemer motifs, which is similar to the competition between hydrogen-bonded dimer and catemer motifs between carboxyl groups (Beyer & Price; 2000 ) or carboxamide groups (Arlin et al., 2010 , 2011 ).

Closer inspection of the geometric possibilities (Fig. 4) shows that dimer formation is feasible for N—H⋯O=C2 and N—H⋯O=C4 connections only, whereas N—H⋯O=C6 should be the preferred connection mode for chain formation. Indeed, five crystal structures containing N—H⋯O=C6 chain motifs are known and their CSD refcodes are DMCYBA01 (Nichol & Clegg, 2005 ), DULMED (Gelbrich et al., 2010 ), MDEBAR (Wunderlich, 1973 ), MIBABA (Wilhelm & Fischer, 1976 ), OBIPUM (Gelbrich & Griesser, 2009 ). So far, the crystal structure with refcode VEMQUB (Savechenkov et al., 2012 ) is the only example in the set where another chain type, viz. N—H⋯O=C2, is present.

Figure 4
The three fundamental connection modes for the formation of N—H⋯O=C bonds in 1-substituted derivatives of barbituric acid arising from the involvement of different carbonyl groups, and the corresponding numbers of observed dimer and catemer isomers. The (S_bR_h) form of methohexithal contains a dimer with mixed N—H⋯O=C2/N—H⋯O=C4 connectivity and was therefore not included.

Apart from the title structure, two analogues with refcodes CXALBA (Dideberg et al., 1975 ) and DULMAZ (Gelbrich et al., 2010) also form N—H⋯O=C2 bonded dimers. The alternative N—H⋯O=C4 dimer was observed in the two structures with refcodes ALLBTC (Pyżalska et al., 1980 ) and MEPBAB01 (Lewis et al., 2005 ). The (S_bR_h) form of methohexital provides the only case of a dimer based on a mixed N—H⋯O=C2/N—H⋯O=C4 connectivity.

5. Synthesis and crystallization

The crystals investigated in this study were obtained at room temperature, by slow evaporation from an aqueous solution of the α-racemate of methohexital (Lilly Research Centre Ltd., Windlesham, England).

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. H atoms were identified in difference maps. The H atoms of the C14 methyl group and disordered C1 methyl group [occupancy ratio 0.57 (2):0.43 (2)] were idealized and included as rigid groups allowed to rotate but not tip (C—H = 0.96 Å) and refined with U_iso set to 1.5U_eq(C) of the parent carbon atom. H atoms bonded to secondary CH₂ (C—H = 0.97 Å), tertiary CH (C—H = 0.98 Å) carbon and aromatic CH carbon atoms (C—H = 0.93 Å) were positioned geometrically and refined with U_iso set to 1.2U_eq(C) of the parent carbon atom. The NH hydrogen atom was refined with a restrained distance [N—H = 0.86 (2) Å] and its U_iso parameter was freely refined.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₄H₁₈N₂O₃
M_r	262.30
Crystal system, space group	Triclinic, P $[\overline{1}]$
Temperature (K)	293
a, b, c (Å)	7.7502 (6), 7.9792 (5), 12.6881 (10)
α, β, γ (°)	93.713 (6), 96.226 (6), 113.314 (7)
V (Å³)	711.32 (10)
Z	2
Radiation type	Mo Kα
μ (mm⁻¹)	0.09
Crystal size (mm)	0.35 × 0.20 × 0.20

Data collection
Diffractometer	Agilent Xcalibur (Ruby, Gemini ultra)
Absorption correction	Multi-scan (CrysAlis PRO; Agilent, 2012 )
T_min, T_max	0.883, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	6896, 3363, 2462
R_int	0.022
(sin θ/λ)_max (Å⁻¹)	0.690

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.049, 0.135, 1.05
No. of reflections	3363
No. of parameters	180
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.22, −0.20
Computer programs: CrysAlis PRO (Agilent, 2012), SHELXS97 (Sheldrick, 2008 ), SHELXL2014/6 (Sheldrick, 2015 ), XP in SHELXTL (Sheldrick, 2008), Mercury (Macrae et al., 2006 ) and publCIF (Westrip, 2010 ).

Supporting information

CCDC reference: 1044166

Crystal structure: contains datablock I. DOI: 10.1107/S205698901500105X/wm5105sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S205698901500105X/wm5105Isup2.hkl

Supporting information file. DOI: 10.1107/S205698901500105X/wm5105Isup3.cml

checkCIF report

Chemical context top

The title compound is a barbiturate derivative, the Na salt of which (trade name Brevimytal, Eli Lilly) is a widely used short-acting anaesthetic with a rapid onset of action. The molecule contains two asymmetric centres and can exist as two diastereomeric enantiomer pairs. Its stereoisomerism is known to affect the anaesthetic activity and possible side effects of the drug (Gibson et al., 1959). The crystal structure of the (S_bR_h) form of methohexital was previously reported by Brunner et al. (2003), who also established that the commercial product (α-racemate) consists of the (R_bS_h) and (S_bR_h) isomers.

Structural commentary top

This study confirmed the presence of the (R_bS_h)/(S_bR_h) racemate. The molecule (Fig. 1) displays an approximately planar pyrimidinetrione unit in which the oxygen atoms of the C2 and C4 carbonyl groups lie at distances of –0.160 (2) and 0.156 (2) Å from the least-squares plane of the six-membered ring (r.m.s. deviation = 0.046 Å). The conformation of the two 5-substituents of the ring is characterized by three parameters, the torsion angles C5—C7—C8—C9 of –103.3 (2) and C10—C5—C7—C8 of –171.51 (13)° and the pseudo-torsion angle C5—C10···C13–C14 of 23.2 (2)°.

The previously reported (S_bR_h) form contains two independent molecules (denoted A and B), which differ from the molecule of the title structure in the conformation adopted by the terminal groups of both 5-substituents (Fig. 2). Specifically, in molecule A, the torsion angle analogous to C5—C7—C8—C9 in the present α-racemate is 125.3°, and the pseudo-torsion angles analogous to C5—C10···C13—C14 of the title structure are –15.4° (A) and –26.3° (B).

Supramolecular features top

Two molecules are linked to one another by two mutual antiparallel N—H···O═ C bonds so that an inversion dimer is formed (Table 1, Fig. 3), which displays a central R₂²(8) ring motif (Etter et al., 1990; Bernstein et al., 1995). This interaction involves the carbonyl group at the 2-position of the ring. The R₂²(8) ring motif is also present in the (S_bR_h) form (Brunner et al., 2003) where it connects the two crystallographically independent molecules. However, in this case the dimer is based on two topologically distinct N—H···O═C interactions which involve the carbonyl groups at the 4-position of the ring of molecule A and at the 2-position of molecule B.

Database survey top

The Cambridge Structural Database (Groom & Allen, 2014; Version 3.35) contains 11 unique entries for derivatives of barbituric acid which are analogous to the title compound and substituted at the 1-position, but not at the 3-position of the six-membered ring. A common characteristic of these compounds is the presence of one hydrogen-bond donor group (NH) and three potential acceptor groups, viz. the carbonyl groups at the ring positions 2, 4 and 6. Thus, three topologically distinct hydrogen-bonding acceptor interactions are possible. Additionally, there is a competition between possible dimer and catemer motifs, which are similar to the competition between hydrogen-bonded dimer and catemer motifs between carboxyl groups (Beyer & Price; 2000) or carboxamide groups (Arlin et al., 2010, 2011).

Closer inspection of the geometric possibilities (Fig. 4) shows that dimer formation is feasible for N—H···O═C2 and N—H···O═C4 connections only, whereas N—H···O═C6 should be the preferred connection mode for chain formation. Indeed, five crystal structures containing N—H···O═C6 chain motifs are known and their CSD refcodes are DMCYBA01 (Nichol & Clegg, 2005), DULMED (Gelbrich et al., 2010), MDEBAR (Wunderlich, 1973), MIBABA (Wilhelm & Fischer, 1976), OBIPUM (Gelbrich & Griesser, 2009). So far, the crystal structure with refcode VEMQUB (Savechenkov et al., 2012) is the only example in the set where another chain type, viz. N—H···O═C2, is present.

Apart from the title structure, two analogues with refcodes CXALBA (Dideberg et al., 1975) and DULMAZ (Gelbrich et al., 2010) also form N—H···O═C2 bonded dimers. The alternative N—H···O═C4 dimer was observed in the two structures with refcodes ALLBTC (Pyżalska et al., 1980) and MEPBAB01 (Lewis et al., 2005). The (S_bR_h) form of methohexital provides the only case of a dimer based on a mixed N—H···O═ C2/N—H···O═C4 connectivity.

Synthesis and crystallization top

Refinement top

Related literature top

For related literature, see: Arlin et al. (2010, 2011); Bernstein et al. (1995); Beyer & Price (2000); Brunner et al. (2003); Dideberg et al. (1975); Etter et al. (1990); Gelbrich & Griesser (2009); Gelbrich et al. (2010); Gibson et al. (1959); Groom & Allen (2014); Lewis et al. (2005); Nichol & Clegg (2005); Pyżalska et al. (1980); Savechenkov et al. (2012); Wilhelm & Fischer (1976); Wunderlich (1973).

Computing details top

Data collection: CrysAlis PRO (Agilent, 2012); cell refinement: CrysAlis PRO (Agilent, 2012); data reduction: CrysAlis PRO (Agilent, 2012); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014/6 (Sheldrick, 2015); molecular graphics: XP in SHELXTL (Sheldrick, 2008) and Mercury (Macrae et al., 2006); software used to prepare material for publication: publCIF (Westrip, 2010).

Figures top

	Fig. 1. The molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level; hydrogen atoms are drawn as spheres of arbitrary size.
	Fig. 2. Overlay of the molecule of the α-racemate (denoted X) with the two independent molecules (A, B) of the previously reported (S_bR_h) form, generated by least-squares fits of their 1-methyl-2,4,6-pyrimidinetrione units (ten non-H atomic positions).
	Fig. 3. The N—H···O═C hydrogen-bonded inversion dimer displaying a central R₂²(8) ring. These interactions (dotted lines) involve the carbonyl group at the 2-position of the six-membered ring. O and H atoms engaged in hydrogen bonding are drawn as spheres.
	Fig. 4. The three fundamental connection modes for the formation of N—H···O═C bonds in 1-substituted derivatives of barbituric acid arising from the involvement of different carbonyl groups, and the corresponding numbers of observed dimer and catemer isomers. The (S_bR_h) form of methohexithal contains a dimer with mixed N—H···O═C2/N—H···O═C4 connectivity and was therefore not included.

5-Allyl-5-(hex-3-yn-2-yl)-1-methylpyrimidine-2,4,6(1H,3H,5H)-trione top

Crystal data top

C₁₄H₁₈N₂O₃	Z = 2
M_r = 262.30	F(000) = 280
Triclinic, P1	D_x = 1.225 Mg m⁻³
a = 7.7502 (6) Å	Mo Kα radiation, λ = 0.71073 Å
b = 7.9792 (5) Å	Cell parameters from 1814 reflections
c = 12.6881 (10) Å	θ = 4.4–28.8°
α = 93.713 (6)°	µ = 0.09 mm⁻¹
β = 96.226 (6)°	T = 293 K
γ = 113.314 (7)°	Prism, colourless
V = 711.32 (10) Å³	0.35 × 0.20 × 0.20 mm

Data collection top

Agilent Xcalibur (Ruby, Gemini ultra) diffractometer	3363 independent reflections
Radiation source: Enhance (Mo) X-ray Source	2462 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.022
Detector resolution: 10.3575 pixels mm^-1	θ_max = 29.4°, θ_min = 2.8°
ω scans	h = −9→10
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2012)	k = −11→9
T_min = 0.883, T_max = 1.000	l = −16→15
6896 measured reflections

Refinement top

Refinement on F²	0 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.049	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.135	w = 1/[σ²(F_o²) + (0.0572P)² + 0.1234P] where P = (F_o² + 2F_c²)/3
S = 1.05	(Δ/σ)_max < 0.001
3363 reflections	Δρ_max = 0.22 e Å⁻³
180 parameters	Δρ_min = −0.20 e Å⁻³

Crystal data top

C₁₄H₁₈N₂O₃	γ = 113.314 (7)°
M_r = 262.30	V = 711.32 (10) Å³
Triclinic, P1	Z = 2
a = 7.7502 (6) Å	Mo Kα radiation
b = 7.9792 (5) Å	µ = 0.09 mm⁻¹
c = 12.6881 (10) Å	T = 293 K
α = 93.713 (6)°	0.35 × 0.20 × 0.20 mm
β = 96.226 (6)°

Data collection top

Agilent Xcalibur (Ruby, Gemini ultra) diffractometer	3363 independent reflections
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2012)	2462 reflections with I > 2σ(I)
T_min = 0.883, T_max = 1.000	R_int = 0.022
6896 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.049	0 restraints
wR(F²) = 0.135	H atoms treated by a mixture of independent and constrained refinement
S = 1.05	Δρ_max = 0.22 e Å⁻³
3363 reflections	Δρ_min = −0.20 e Å⁻³
180 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. The C1 methyl group is disordered over two positions.

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

	x	y	z	U_iso*/U_eq	Occ. (<1)
N1	−0.00769 (16)	−0.12155 (16)	0.75511 (9)	0.0382 (3)
N3	0.15035 (17)	0.08665 (17)	0.63981 (10)	0.0412 (3)
H3	0.145 (2)	0.115 (2)	0.5763 (16)	0.055 (5)*
O2	−0.12784 (15)	−0.15309 (16)	0.58085 (9)	0.0582 (4)
O4	0.42793 (15)	0.32706 (15)	0.69135 (9)	0.0546 (3)
O6	0.12730 (17)	−0.09825 (17)	0.92461 (9)	0.0589 (3)
C1	−0.1759 (2)	−0.2810 (2)	0.77286 (14)	0.0550 (4)
H1A	−0.1624	−0.3036	0.8461	0.082*	0.43 (2)
H1B	−0.2871	−0.2566	0.7570	0.082*	0.43 (2)
H1C	−0.1881	−0.3870	0.7272	0.082*	0.43 (2)
H1D	−0.2627	−0.3279	0.7074	0.082*	0.57 (2)
H1E	−0.1380	−0.3749	0.7965	0.082*	0.57 (2)
H1F	−0.2370	−0.2445	0.8263	0.082*	0.57 (2)
C2	−0.0015 (2)	−0.06791 (19)	0.65385 (11)	0.0393 (3)
C4	0.30668 (19)	0.18923 (19)	0.71322 (11)	0.0376 (3)
C5	0.32002 (19)	0.11774 (19)	0.82021 (11)	0.0368 (3)
C6	0.1393 (2)	−0.04093 (19)	0.83867 (11)	0.0383 (3)
C7	0.3687 (2)	0.2764 (2)	0.90965 (12)	0.0460 (4)
H7A	0.3993	0.2375	0.9775	0.055*
H7B	0.4802	0.3803	0.8970	0.055*
C8	0.2092 (2)	0.3359 (2)	0.91640 (13)	0.0527 (4)
H8	0.1068	0.2623	0.9479	0.063*
C9	0.2045 (3)	0.4828 (3)	0.88144 (18)	0.0759 (6)
H9A	0.3047	0.5594	0.8496	0.091*
H9B	0.1010	0.5118	0.8882	0.091*
C10	0.4766 (2)	0.0383 (2)	0.82568 (12)	0.0463 (4)
H10	0.4680	−0.0253	0.8897	0.057 (5)*
C11	0.4322 (2)	−0.1006 (2)	0.73331 (14)	0.0510 (4)
C12	0.3973 (3)	−0.2041 (3)	0.65519 (17)	0.0620 (5)
C13	0.3521 (4)	−0.3299 (3)	0.55608 (19)	0.0882 (7)
H13A	0.4699	−0.3204	0.5319	0.106*
H13B	0.2858	−0.4551	0.5716	0.106*
C14	0.2356 (5)	−0.2930 (4)	0.4700 (2)	0.1143 (10)
H14A	0.2091	−0.3809	0.4086	0.171*
H14B	0.3027	−0.1714	0.4518	0.171*
H14C	0.1185	−0.3025	0.4931	0.171*
C15	0.6801 (2)	0.1819 (3)	0.83485 (16)	0.0640 (5)
H15A	0.7656	0.1217	0.8353	0.096*
H15B	0.7106	0.2628	0.8999	0.096*
H15C	0.6922	0.2517	0.7751	0.096*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0343 (6)	0.0402 (6)	0.0336 (6)	0.0085 (5)	0.0022 (5)	0.0091 (5)
N3	0.0409 (7)	0.0458 (7)	0.0270 (6)	0.0083 (5)	−0.0027 (5)	0.0108 (5)
O2	0.0463 (6)	0.0661 (7)	0.0372 (6)	−0.0001 (5)	−0.0087 (5)	0.0094 (5)
O4	0.0494 (6)	0.0501 (6)	0.0469 (7)	0.0019 (5)	0.0011 (5)	0.0168 (5)
O6	0.0592 (7)	0.0696 (8)	0.0345 (6)	0.0109 (6)	0.0028 (5)	0.0210 (5)
C1	0.0428 (8)	0.0541 (9)	0.0541 (10)	0.0037 (7)	0.0054 (7)	0.0182 (8)
C2	0.0366 (7)	0.0430 (8)	0.0328 (8)	0.0117 (6)	−0.0010 (6)	0.0069 (6)
C4	0.0357 (7)	0.0389 (7)	0.0326 (7)	0.0100 (6)	0.0014 (6)	0.0072 (6)
C5	0.0351 (7)	0.0424 (7)	0.0276 (7)	0.0115 (6)	−0.0017 (5)	0.0054 (5)
C6	0.0396 (7)	0.0429 (8)	0.0302 (7)	0.0143 (6)	0.0026 (6)	0.0081 (6)
C7	0.0433 (8)	0.0508 (9)	0.0329 (8)	0.0110 (7)	−0.0046 (6)	−0.0011 (6)
C8	0.0504 (9)	0.0550 (10)	0.0433 (9)	0.0138 (8)	0.0031 (7)	−0.0034 (7)
C9	0.0711 (13)	0.0635 (12)	0.0904 (16)	0.0273 (10)	0.0032 (11)	0.0041 (11)
C10	0.0434 (8)	0.0571 (9)	0.0387 (8)	0.0215 (7)	−0.0007 (6)	0.0112 (7)
C11	0.0491 (9)	0.0562 (10)	0.0533 (10)	0.0268 (8)	0.0064 (8)	0.0122 (8)
C12	0.0633 (11)	0.0639 (11)	0.0663 (12)	0.0352 (9)	0.0044 (9)	0.0051 (9)
C13	0.1023 (18)	0.0897 (16)	0.0816 (16)	0.0565 (14)	−0.0012 (14)	−0.0187 (13)
C14	0.146 (3)	0.130 (2)	0.0667 (16)	0.064 (2)	0.0027 (17)	−0.0222 (15)
C15	0.0396 (9)	0.0777 (12)	0.0671 (12)	0.0194 (9)	−0.0034 (8)	0.0029 (10)

Geometric parameters (Å, º) top

N1—C2	1.3800 (18)	C7—H7A	0.9700
N1—C6	1.3804 (17)	C7—H7B	0.9700
N1—C1	1.4687 (18)	C8—C9	1.292 (3)
N3—C2	1.3648 (18)	C8—H8	0.9300
N3—C4	1.3701 (17)	C9—H9A	0.9300
N3—H3	0.85 (2)	C9—H9B	0.9300
O2—C2	1.2140 (16)	C10—C11	1.471 (2)
O4—C4	1.2032 (17)	C10—C15	1.526 (2)
O6—C6	1.2083 (17)	C10—H10	0.9800
C1—H1A	0.9600	C11—C12	1.182 (2)
C1—H1B	0.9600	C12—C13	1.474 (3)
C1—H1C	0.9600	C13—C14	1.460 (3)
C1—H1D	0.9600	C13—H13A	0.9700
C1—H1E	0.9600	C13—H13B	0.9700
C1—H1F	0.9600	C14—H14A	0.9600
C4—C5	1.5151 (18)	C14—H14B	0.9600
C5—C6	1.5248 (19)	C14—H14C	0.9600
C5—C7	1.541 (2)	C15—H15A	0.9600
C5—C10	1.574 (2)	C15—H15B	0.9600
C7—C8	1.498 (2)	C15—H15C	0.9600

C2—N1—C6	123.81 (12)	O6—C6—C5	120.29 (12)
C2—N1—C1	117.84 (12)	N1—C6—C5	119.14 (12)
C6—N1—C1	118.24 (12)	C8—C7—C5	112.61 (12)
C2—N3—C4	127.42 (12)	C8—C7—H7A	109.1
C2—N3—H3	113.2 (12)	C5—C7—H7A	109.1
C4—N3—H3	119.3 (12)	C8—C7—H7B	109.1
N1—C1—H1A	109.5	C5—C7—H7B	109.1
N1—C1—H1B	109.5	H7A—C7—H7B	107.8
H1A—C1—H1B	109.5	C9—C8—C7	124.36 (18)
N1—C1—H1C	109.5	C9—C8—H8	117.8
H1A—C1—H1C	109.5	C7—C8—H8	117.8
H1B—C1—H1C	109.5	C8—C9—H9A	120.0
N1—C1—H1D	109.5	C8—C9—H9B	120.0
H1A—C1—H1D	141.1	H9A—C9—H9B	120.0
H1B—C1—H1D	56.3	C11—C10—C15	110.95 (15)
H1C—C1—H1D	56.3	C11—C10—C5	109.25 (12)
N1—C1—H1E	109.5	C15—C10—C5	114.96 (14)
H1A—C1—H1E	56.3	C11—C10—H10	107.1
H1B—C1—H1E	141.1	C15—C10—H10	107.1
H1C—C1—H1E	56.3	C5—C10—H10	107.1
H1D—C1—H1E	109.5	C12—C11—C10	176.00 (18)
N1—C1—H1F	109.5	C11—C12—C13	178.4 (2)
H1A—C1—H1F	56.3	C14—C13—C12	113.7 (2)
H1B—C1—H1F	56.3	C14—C13—H13A	108.8
H1C—C1—H1F	141.1	C12—C13—H13A	108.8
H1D—C1—H1F	109.5	C14—C13—H13B	108.8
H1E—C1—H1F	109.5	C12—C13—H13B	108.8
O2—C2—N3	121.50 (13)	H13A—C13—H13B	107.7
O2—C2—N1	121.22 (13)	C13—C14—H14A	109.5
N3—C2—N1	117.27 (12)	C13—C14—H14B	109.5
O4—C4—N3	120.57 (12)	H14A—C14—H14B	109.5
O4—C4—C5	122.59 (12)	C13—C14—H14C	109.5
N3—C4—C5	116.82 (12)	H14A—C14—H14C	109.5
C4—C5—C6	114.41 (11)	H14B—C14—H14C	109.5
C4—C5—C7	108.82 (12)	C10—C15—H15A	109.5
C6—C5—C7	108.29 (12)	C10—C15—H15B	109.5
C4—C5—C10	108.59 (12)	H15A—C15—H15B	109.5
C6—C5—C10	105.19 (11)	C10—C15—H15C	109.5
C7—C5—C10	111.55 (11)	H15A—C15—H15C	109.5
O6—C6—N1	120.54 (13)	H15B—C15—H15C	109.5

C10—C5—C7—C8	−171.51 (13)	C5—C7—C8—C9	−103.3 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3···O2ⁱ	0.85 (2)	2.03 (2)	2.8826 (17)	173.2 (17)

Symmetry code: (i) −x, −y, −z+1.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3···O2ⁱ	0.85 (2)	2.03 (2)	2.8826 (17)	173.2 (17)

Symmetry code: (i) −x, −y, −z+1.

Experimental details

Crystal data
Chemical formula	C₁₄H₁₈N₂O₃
M_r	262.30
Crystal system, space group	Triclinic, P1
Temperature (K)	293
a, b, c (Å)	7.7502 (6), 7.9792 (5), 12.6881 (10)
α, β, γ (°)	93.713 (6), 96.226 (6), 113.314 (7)
V (Å³)	711.32 (10)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.35 × 0.20 × 0.20

Data collection
Diffractometer	Agilent Xcalibur (Ruby, Gemini ultra) diffractometer
Absorption correction	Multi-scan (CrysAlis PRO; Agilent, 2012)
T_min, T_max	0.883, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	6896, 3363, 2462
R_int	0.022
(sin θ/λ)_max (Å⁻¹)	0.690

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.049, 0.135, 1.05
No. of reflections	3363
No. of parameters	180
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.22, −0.20

Computer programs: CrysAlis PRO (Agilent, 2012), SHELXS97 (Sheldrick, 2008), SHELXL2014/6 (Sheldrick, 2015), XP in SHELXTL (Sheldrick, 2008) and Mercury (Macrae et al., 2006), publCIF (Westrip, 2010).

Acknowledgements

We thank Volker Kahlenberg for access to the X-ray diffraction instrument used in this study.

References

Agilent (2012). CrysAlis PRO. Agilent Technologies, Yarnton, England. Google Scholar
Arlin, J.-B., Johnston, A., Miller, G. J., Kennedy, A. R., Price, S. L. & Florence, A. J. (2010). CrystEngComm 12, 64–66. Google Scholar
Arlin, J.-B., Price, L. S., Price, S. L. & Florence, A. J. (2011). Chem. Commun. 47, 7074–7076. Web of Science CSD CrossRef CAS Google Scholar
Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555–1573. CrossRef CAS Web of Science Google Scholar
Beyer, T. & Price, S. L. (2000). J. Phys. Chem. B, 104, 2647–2655. Web of Science CrossRef CAS Google Scholar
Brunner, H., Ittner, K.-P., Lunz, D., Schmatloch, S., Schmidt, T. & Zabel, M. (2003). Eur. J. Org. Chem. pp. 855–862. CSD CrossRef Google Scholar
Dideberg, O., Dupont, L. & Pyzalska, D. (1975). Acta Cryst. B31, 685–688. CSD CrossRef CAS IUCr Journals Web of Science Google Scholar
Etter, M. C., MacDonald, J. C. & Bernstein, J. (1990). Acta Cryst. B46, 256–262. CrossRef CAS Web of Science IUCr Journals Google Scholar
Gelbrich, T. & Griesser, U. (2009). Private communication (refcode OBIPUM). CCDC, Cambridge, England. Google Scholar
Gelbrich, T., Zencirci, N. & Griesser, U. J. (2010). Acta Cryst. C66, o55–o58. Web of Science CSD CrossRef IUCr Journals Google Scholar
Gibson, W. R., Doran, W. J., Wood, W. C. & Swanson, E. E. (1959). J. Pharmacol. Exp. Ther. 125, 23–27. Google Scholar
Groom, C. R. & Allen, F. H. (2014). Angew. Chem. Int. Ed. 53, 115–121. Google Scholar
Lewis, W., McKeown, R. H. & Robinson, W. T. (2005). Acta Cryst. E61, o799–o800. Web of Science CSD CrossRef IUCr Journals Google Scholar
Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453–457. Web of Science CrossRef CAS IUCr Journals Google Scholar
Nichol, G. S. & Clegg, W. (2005). Acta Cryst. E61, o1004–o1006. Web of Science CSD CrossRef IUCr Journals Google Scholar
Pyżalska, D., Pyżalski, R. & Borowiak, T. (1980). Acta Cryst. B36, 1672–1675. CSD CrossRef IUCr Journals Web of Science Google Scholar
Savechenkov, P. Y., Zhang, X., Chiara, D. C., Stewart, D. S., Ge, R., Zhou, X., Raines, D. E., Cohen, J. B., Forman, S. A., Miller, K. W. & Bruzik, K. S. (2012). J. Med. Chem. 55, 6554–6565. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2015). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925. Web of Science CrossRef CAS IUCr Journals Google Scholar
Wilhelm, E. & Fischer, K. F. (1976). Cryst. Struct. Commun. 5, 507–510. CAS Google Scholar
Wunderlich, H. (1973). Acta Cryst. B29, 168–173. Google Scholar

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Volume 71| Part 2| February 2015| Pages 206-209

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