tert-Butyl 2-(3-acetyl­amino-2-oxo-1,2-dihydro-1-pyrid­yl)acetate

Karis, N.D.; Loughlin, W.A.; Jenkins, I.D.; Healy, P.C.

doi:10.1107/S1600536808039810

organic compounds

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ISSN: 2056-9890

Volume 64| Part 12| December 2008| Pages o2492-o2493

doi:10.1107/S1600536808039810

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tert-Butyl 2-(3-acetylamino-2-oxo-1,2-dihydro-1-pyridyl)acetate

N. David Karis,^a Wendy A. Loughlin,^b Ian D. Jenkins ^a and Peter C. Healy ^b ^*

^aEskitis Institute for Cell and Molecular Therapies, Griffith University, Nathan, Brisbane 4111, Australia, and ^bSchool of Biomolecular and Physical Sciences and Eskitis Institute for Cell and Molecular Therapies, Griffith University, Nathan, Brisbane 4111, Australia
^*Correspondence e-mail: P.Healy@griffith.edu.au

(Received 24 November 2008; accepted 25 November 2008; online 29 November 2008)

The title compound, C₁₃H₁₈N₂O₄, crystallizes as discrete molecules associated as N—H⋯O hydrogen-bonded dimers disposed about a crystallographic inversion centre. The structure is the first solid-state structure for a 3-acetylpyridone without C-4 to C-6 substituents. The amide subsituent at C-3 is coplanar with the pyridone ring, while the tert-butyl ester group is orthogonal to the pyridine ring. The amide and ester carbonyl O atoms are not involved in strong hydrogen bonding with only a number of intramolecular and intermolecular C—H⋯O interactions apparent in the structure.

Related literature

For general background, see: Bernstein et al. (1994 ); Dragovich et al. (2002 ); Hu et al. (2008 ); Karis et al. (2007 ); Kim et al. (2008 ); Loughlin et al. (2004 ); Reiner et al. (1999 ); Semple et al. (1998 ); Veale et al. (1995 ). For the synthesis, see: Sanderson et al. (1997 ); Tamura et al. (1996 ). For related structures. see: Karis et al. (2006 ); Yang & Craven (1998 ).

Experimental

Crystal data

C₁₃H₁₈N₂O₄
M_r = 266.29
Monoclinic, P 2₁ /c
a = 13.9417 (15) Å
b = 5.585 (1) Å
c = 17.861 (2) Å
β = 97.039 (9)°
V = 1380.3 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 295 (2) K
0.40 × 0.30 × 0.20 mm

Data collection

Rigaku AFC-7R diffractometer
Absorption correction: none
2731 measured reflections
2428 independent reflections
1482 reflections with I > 2σ(I)
R_int = 0.046
3 standard reflections every 150 reflections intensity decay: 0.6%

Refinement

R[F² > 2σ(F²)] = 0.052
wR(F²) = 0.162
S = 1.02
2428 reflections
176 parameters
H-atom parameters constrained
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.27 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N3—H3⋯O2ⁱ	0.86	2.34	3.164 (3)	161
C4—H4⋯O3	0.95	2.23	2.830 (3)	120
C14—H14A⋯O3ⁱⁱ	0.96	2.56	3.465 (4)	157
C15—H15A⋯O11	0.96	2.44	2.980 (4)	115
C16—H16A⋯O11	0.96	2.44	2.978 (5)	115
C32—H32C⋯O2ⁱ	0.96	2.33	3.222 (3)	155
Symmetry codes: (i) -x+2, -y+1, -z; (ii) x-1, y, z.

Data collection: MSC/AFC7 Diffractometer Control Software (Molecular Structure Corporation, 1999 $[Molecular Structure Corporation (1999). MSC/AFC7 Diffractometer Control for Windows. MSC, The Woodlands, Texas, USA.]$ ); cell refinement: MSC/AFC7 Diffractometer Control Software; data reduction: TEXSAN for Windows (Molecular Structure Corporation, 2001 ); program(s) used to solve structure: TEXSAN for Windows; program(s) used to refine structure: TEXSAN for Windows and SHELXL97 (Sheldrick, 2008 ); molecular graphics: ORTEP-3 (Farrugia, 1997 ); software used to prepare material for publication: TEXSAN for Windows and PLATON (Spek, 2003 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808039810/bt2816sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808039810/bt2816Isup2.hkl

checkCIF report

Comment top

Increased binding affinity of pyridone based scaffolds as P4—P2 conformational restraints (Dragovich et al., 2002; Reiner et al., 1999; Semple et al., 1998; Veale et al., 1995; Bernstein et al., 1994) in peptidiomimetics (Loughlin et al., 2004, and references therein) is often associated with the substituent functionality at N1 and C3 of the pyridone ring. This has been reflected by enzyme-ligand crystal structures of a C3-amidoaryl pyridone with human rhinovirus (HRV) 3 C protease (3CP) (Dragovich et al., 2002), and a C3-sulfonylamide pyridone with porcine pancreatic elastase (Bernstein et al., 1994). Similiarly, other enzyme-ligand interactions have been observed in the solid state with kinases; a N1-aryl pyridone with Met kinase (Kim et al., 2008) and a N1-aryl C3-aryl pyridone with KDR kinase (Hu et al., 2008). Thus an understanding of the structure of substituted pyridone compounds is important. Elsewhere, the facile synthesis of N1, C3-substituted pyridones is reported (Karis et al., 2007). Herein we report the first solid state structure (II) for a 3-acetylpyridone without C4 to C6 substituents.

The structure of (II) consists of discrete molecular units (Fig. 1) which form N3—H3···O2 hydrogen bonded dimers disposed about a crystallographic centre of symmetry (Figure 2, Table 1). The amide N3—C31—O3—C32 is co-planar with the pyridone ring with the O3···H4 contact distance 2.23 Å. The tert-butyl ester group attached to N1 lies orthogonal to the pyridone ring with the C2—N1—C11—C12 torsion angle -81.1 (2)°. The geometry of the pyridone ring is in accord with related structures (Yang & Craven, 1998; Karis et al., 2006) with the C2—C3 distance 1.440 (3)Å while the other C—C and C—N distance range from 1.333 (4) - 1.402 (4) Å. The N3—C31 distance of 1.362 (3)Å is shorter than the N3—C3 distance of 1.399 (3) Å; indicating a preference for involvement of N3 in conjugation with the amide rather than the pyridone. The carbonyl groups C31—O3 and C21—O11 are not involved in strong hydrogen bonding interactions with only a number of C—H···O interactions apparent in the crystal lattice (Table 2).

Related literature top

For related literature, see: Bernstein et al. (1994); Dragovich et al. (2002); Hu et al. (2008); Karis et al. (2006, 2007); Kim et al. (2008); Loughlin et al. (2004); Reiner et al. (1999); Sanderson et al. (1997); Semple et al. (1998); Tamura et al. (1996); Veale et al. (1995); Yang & Craven (1998). It would be much more useful to readers if the "Related literature" section had some kind of simple sub-division, so that, instead of just "For related literature, see···" it said, for example, "For general background, see···. For related structures, see···.? etc. Please revise this section as indicated.

Experimental top

Tert-Butyl 2-(3'-amino-2'-oxopyridin-1'(2H)-yl)acetate (compound (I)) was prepared by N-alkylation of nitropyridone with sodium hydride and tert-butyl bromoacetate (Sanderson et al., 1997; Tamura et al., 1996), and subsequent hydrogenation over palladium-on-carbon (Tamura et al., 1996).

For the preparation of compound (II), compound (I) (0.78 g, 3.48 mmol) was dissolved in a mixture of dry dichloromethane (10 ml) and triethylamine (0.97 ml, 6.96 mmol) under nitrogen. Acetyl chloride (0.50 ml, 6.96 mmol) was added dropwise at 295 K. The resulting mixture was stirred for 4 h and then concentrated to give a suspension of the product and triethylamine hydrochloride. The suspension was directly transferred to a silica gel column using dichloromethane with 0.5% triethylamine and eluted with an ethyl acetate /dichloromethane gradient (0 to 20% ethyl acetate, with 0.5% triethyl amine. Red crystals of (II) (m.p. 415–418 K) (0.91 g, 98%) were isolated by slow evaporation from an ethyl acetate /dichloromethane solution. Analysis found: C 58.73, H 6.84, N 10.36%; calculated for C₁₃H₁₈N₂O₄: C 58.64, H 6.81, N 10.52%. ν_max(KBr) cm^-1 3318, 2974, 1716, 1646, 1605, 1532, 1512. δ_H (400 MHz, CDCl₃, p.p.m.) 1.49 (9H, s, C(CH₃)₃), 2.19 (3H, s, CH₃), 4.58 (2H, s, H2), 6.27 (1H, dd, J = 7.0, 7.0 Hz, H5'), 6.92 (1H, dd, J = 7.0, 1.6 Hz, H6'), 8.35 (1H, brs, W_h1/2 = 11 Hz, NH), 8.39 (1H, dd, J = 7.2, 1.6 Hz, H4'). δ_C (100 MHz, CDCl₃) 24.7 (CH₃), 28.0 (C(CH₃)₃), 51.6 (C2), 83.1 (C(CH₃)₃), 106.8 (C5'), 122.4 (C4'), 129.3 (C3'), 130.2 (C6'), 157.4 (C2'), 166.2 (C1), 169.0 (CO). MS (ES⁺) 289.2 (MNa⁺, 30%) 273.2 (MLi⁺, 40%).

Computing details top

Data collection: MSC/AFC7 Diffractometer Control Software (Molecular Structure Corporation, 1999); cell refinement: MSC/AFC7 Diffractometer Control Software (Molecular Structure Corporation, 1999); data reduction: TEXSAN for Windows (Molecular Structure Corporation, 2001); program(s) used to solve structure: TEXSAN for Windows (Molecular Structure Corporation, 2001); program(s) used to refine structure: TEXSAN for Windows (Molecular Structure Corporation, 2001) and SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: TEXSAN for Windows (Molecular Structure Corporation, 2001) and PLATON (Spek, 2003).

Figures top

	Fig. 1. View of the molecular structure of (II) with the atom numbering scheme. Displacement ellipsoids for non-H atoms are drawn at the 30% probability level. H atoms are presented as small spheres of arbitrary radii.
	Fig. 2. View of the dimeric structure of (II).
	Fig. 3. The formation of the title compound.

tert-Butyl 2-(3-acetylamino-2-oxo-1,2-dihydro-1-pyridyl)acetate top

Crystal data top

C₁₃H₁₈N₂O₄	F(000) = 568
M_r = 266.29	D_x = 1.281 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71069 Å
Hall symbol: -P 2ybc	Cell parameters from 25 reflections
a = 13.9417 (15) Å	θ = 12.6–17.5°
b = 5.585 (1) Å	µ = 0.10 mm⁻¹
c = 17.861 (2) Å	T = 295 K
β = 97.039 (9)°	Block, red
V = 1380.3 (3) Å³	0.40 × 0.30 × 0.20 mm
Z = 4

Data collection top

Rigaku AFC-7R diffractometer	R_int = 0.046
Radiation source: Rigaku rotating anode	θ_max = 25.0°, θ_min = 2.6°
Graphite monochromator	h = −16→16
ω–2θ scans	k = −6→0
2731 measured reflections	l = −21→10
2428 independent reflections	3 standard reflections every 150 reflections
1482 reflections with I > 2σ(I)	intensity decay: 0.6%

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)] = 0.052	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.162	H-atom parameters constrained
S = 1.02	w = 1/[σ²(F_o²) + (0.0906P)² + 0.0473P] where P = (F_o² + 2F_c²)/3
2428 reflections	(Δ/σ)_max = 0.001
176 parameters	Δρ_max = 0.27 e Å⁻³
0 restraints	Δρ_min = −0.27 e Å⁻³

Crystal data top

C₁₃H₁₈N₂O₄	V = 1380.3 (3) Å³
M_r = 266.29	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 13.9417 (15) Å	µ = 0.10 mm⁻¹
b = 5.585 (1) Å	T = 295 K
c = 17.861 (2) Å	0.40 × 0.30 × 0.20 mm
β = 97.039 (9)°

Data collection top

Rigaku AFC-7R diffractometer	R_int = 0.046
2731 measured reflections	3 standard reflections every 150 reflections
2428 independent reflections	intensity decay: 0.6%
1482 reflections with I > 2σ(I)

Refinement top

R[F² > 2σ(F²)] = 0.052	0 restraints
wR(F²) = 0.162	H-atom parameters constrained
S = 1.02	Δρ_max = 0.27 e Å⁻³
2428 reflections	Δρ_min = −0.27 e Å⁻³
176 parameters

Special details top

Experimental. The scan width was (1.79 + 0.30tanθ)° with an ω scan speed of 16° per minute (up to 4 scans to achieve I/σ(I) > 10). Stationary background counts were recorded at each end of the scan, and the scan time:background time ratio was 2:1.

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement on F² for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The observed criterion of F² > σ(F²) is used only for calculating -R-factor-obs 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
O2	0.93631 (11)	0.2790 (3)	0.03272 (10)	0.0595 (6)
O3	1.26910 (13)	0.2449 (4)	0.15628 (14)	0.0940 (9)
O11	0.79117 (14)	0.2673 (4)	0.16249 (13)	0.0868 (9)
O12	0.66171 (11)	0.0894 (3)	0.09995 (9)	0.0520 (6)
N1	0.91347 (13)	−0.0488 (3)	0.10449 (11)	0.0487 (6)
N3	1.12376 (12)	0.3204 (4)	0.08928 (11)	0.0497 (7)
C2	0.97001 (15)	0.1321 (4)	0.08098 (12)	0.0450 (7)
C3	1.06936 (15)	0.1361 (4)	0.11623 (12)	0.0450 (7)
C4	1.10110 (17)	−0.0279 (5)	0.16998 (14)	0.0546 (8)
C5	1.0390 (2)	−0.2076 (5)	0.19027 (15)	0.0634 (10)
C6	0.94768 (18)	−0.2158 (5)	0.15792 (15)	0.0580 (9)
C11	0.81146 (16)	−0.0501 (4)	0.07545 (14)	0.0508 (8)
C12	0.75508 (16)	0.1222 (4)	0.11859 (14)	0.0505 (8)
C13	0.58947 (17)	0.2243 (5)	0.13832 (15)	0.0569 (9)
C14	0.4945 (2)	0.1252 (7)	0.1020 (2)	0.0982 (15)
C15	0.6042 (2)	0.1659 (8)	0.22108 (18)	0.0934 (14)
C16	0.5968 (3)	0.4858 (6)	0.1224 (3)	0.1150 (18)
C31	1.21909 (17)	0.3673 (5)	0.11050 (15)	0.0577 (9)
C32	1.25913 (17)	0.5768 (6)	0.07310 (16)	0.0683 (10)
H3	1.09400	0.41360	0.05580	0.0590*
H4	1.16570	−0.02040	0.19410	0.0650*
H5	1.06240	−0.32280	0.22700	0.0750*
H6	0.90590	−0.33820	0.17180	0.0690*
H14A	0.44270	0.19330	0.12570	0.1480*
H14B	0.49430	−0.04570	0.10780	0.1480*
H14C	0.48610	0.16470	0.04930	0.1480*
H15A	0.66300	0.23860	0.24400	0.1400*
H15B	0.60820	−0.00460	0.22760	0.1400*
H15C	0.55080	0.22640	0.24460	0.1400*
H16A	0.65600	0.54750	0.14840	0.1730*
H16B	0.54300	0.56810	0.13940	0.1730*
H16C	0.59610	0.50990	0.06910	0.1730*
H32A	1.31990	0.53370	0.05670	0.1030*
H32B	1.26860	0.70740	0.10820	0.1030*
H32C	1.21470	0.62420	0.03030	0.1030*
H111	0.78650	−0.20760	0.07980	0.0610*
H112	0.80430	−0.00530	0.02370	0.0610*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O2	0.0418 (9)	0.0716 (12)	0.0638 (10)	−0.0042 (9)	0.0008 (8)	0.0138 (10)
O3	0.0447 (10)	0.1068 (17)	0.1239 (19)	−0.0035 (11)	−0.0167 (11)	0.0397 (15)
O11	0.0571 (12)	0.0988 (16)	0.1066 (16)	−0.0158 (11)	0.0190 (11)	−0.0554 (14)
O12	0.0417 (9)	0.0507 (10)	0.0646 (10)	0.0020 (7)	0.0110 (7)	−0.0070 (9)
N1	0.0405 (10)	0.0493 (11)	0.0577 (12)	−0.0012 (9)	0.0119 (9)	−0.0033 (10)
N3	0.0332 (10)	0.0621 (13)	0.0531 (11)	0.0032 (9)	0.0028 (8)	0.0019 (10)
C2	0.0375 (11)	0.0517 (14)	0.0468 (12)	0.0008 (11)	0.0096 (10)	−0.0036 (12)
C3	0.0375 (11)	0.0528 (14)	0.0461 (12)	0.0056 (10)	0.0111 (10)	−0.0059 (11)
C4	0.0445 (13)	0.0635 (16)	0.0555 (14)	0.0082 (12)	0.0052 (11)	−0.0015 (13)
C5	0.0629 (16)	0.0598 (17)	0.0673 (17)	0.0109 (14)	0.0076 (13)	0.0107 (14)
C6	0.0583 (15)	0.0487 (15)	0.0680 (16)	0.0000 (12)	0.0118 (13)	0.0020 (13)
C11	0.0404 (12)	0.0517 (14)	0.0614 (14)	−0.0088 (11)	0.0112 (11)	−0.0087 (12)
C12	0.0421 (13)	0.0530 (14)	0.0575 (14)	−0.0060 (11)	0.0100 (11)	−0.0062 (12)
C13	0.0495 (14)	0.0502 (15)	0.0751 (17)	0.0081 (11)	0.0243 (12)	0.0020 (13)
C14	0.0472 (16)	0.105 (3)	0.142 (3)	0.0181 (17)	0.0101 (18)	−0.018 (2)
C15	0.083 (2)	0.122 (3)	0.083 (2)	0.014 (2)	0.0411 (18)	0.010 (2)
C16	0.127 (3)	0.0546 (19)	0.180 (4)	0.024 (2)	0.085 (3)	0.024 (2)
C31	0.0377 (13)	0.0680 (17)	0.0671 (16)	0.0021 (12)	0.0049 (12)	−0.0023 (14)
C32	0.0407 (13)	0.081 (2)	0.0817 (19)	−0.0074 (13)	0.0020 (13)	0.0100 (16)

Geometric parameters (Å, º) top

O2—C2	1.240 (3)	C31—C32	1.489 (4)
O3—C31	1.218 (3)	C4—H4	0.9500
O11—C12	1.195 (3)	C5—H5	0.9500
O12—C12	1.316 (3)	C6—H6	0.9500
O12—C13	1.490 (3)	C11—H111	0.9500
N1—C2	1.378 (3)	C11—H112	0.9500
N1—C6	1.377 (3)	C14—H14A	0.9600
N1—C11	1.453 (3)	C14—H14B	0.9600
N3—C3	1.399 (3)	C14—H14C	0.9600
N3—C31	1.362 (3)	C15—H15A	0.9600
N3—H3	0.8600	C15—H15B	0.9600
C2—C3	1.450 (3)	C15—H15C	0.9600
C3—C4	1.361 (3)	C16—H16A	0.9600
C4—C5	1.402 (4)	C16—H16B	0.9600
C5—C6	1.333 (4)	C16—H16C	0.9600
C11—C12	1.512 (3)	C32—H32A	0.9600
C13—C14	1.507 (4)	C32—H32B	0.9600
C13—C16	1.494 (4)	C32—H32C	0.9600
C13—C15	1.503 (4)

O2···N3	2.694 (2)	C31···H4	2.7800
O2···C12	3.233 (3)	C32···H112ⁱ	3.0200
O2···C32ⁱ	3.222 (3)	H3···O2	2.3100
O2···N3ⁱ	3.164 (3)	H3···H32C	2.1500
O3···C4	2.830 (3)	H3···O2ⁱ	2.3400
O11···C2	3.130 (3)	H4···O3	2.2300
O11···N1	2.744 (3)	H4···C31	2.7800
O11···C15	2.980 (4)	H4···O11^vi	2.8200
O11···C16	2.978 (5)	H5···O11^vi	2.7100
O11···C5ⁱⁱ	3.319 (4)	H5···C5^vi	3.0500
O11···C4ⁱⁱ	3.379 (3)	H5···C6^vi	3.0200
O2···H3	2.3100	H6···O11^vii	2.7200
O2···H32Cⁱ	2.3300	H6···H111	2.3100
O2···H112	2.4200	H6···C4^vi	3.0300
O2···H3ⁱ	2.3400	H14A···O3^viii	2.5600
O3···H4	2.2300	H14A···H15C	2.4600
O3···H14Aⁱⁱⁱ	2.5600	H14A···H16B	2.5100
O3···H15Bⁱⁱ	2.8800	H14B···C16^vii	2.9800
O11···H16A	2.4400	H14B···H15B	2.5100
O11···H6^iv	2.7200	H14B···H16B^vii	2.3100
O11···H15A	2.4400	H14C···H16C	2.4600
O11···H4ⁱⁱ	2.8200	H15A···O11	2.4400
O11···H5ⁱⁱ	2.7100	H15A···C12	2.7900
N1···O11	2.744 (3)	H15A···H16A	2.4200
N3···O2	2.694 (2)	H15B···C12	3.0800
N3···O2ⁱ	3.164 (3)	H15B···H14B	2.5100
N3···H112^v	2.9400	H15B···O3^vi	2.8800
C2···O11	3.130 (3)	H15C···H14A	2.4600
C2···C2^v	3.441 (3)	H16A···O11	2.4400
C4···O3	2.830 (3)	H16A···C12	2.8300
C4···O11^vi	3.379 (3)	H16A···H15A	2.4200
C5···O11^vi	3.319 (4)	H16B···H14A	2.5100
C12···O2	3.233 (3)	H16B···H14B^iv	2.3100
C15···O11	2.980 (4)	H16C···H14C	2.4600
C16···O11	2.978 (5)	H32B···C4^iv	3.0800
C32···O2ⁱ	3.222 (3)	H32C···H3	2.1500
C4···H32B^vii	3.0800	H32C···O2ⁱ	2.3300
C4···H6ⁱⁱ	3.0300	H32C···C11ⁱ	3.0300
C5···H5ⁱⁱ	3.0500	H32C···C12ⁱ	3.0900
C6···H5ⁱⁱ	3.0200	H32C···H112ⁱ	2.3400
C11···H32Cⁱ	3.0300	H111···H6	2.3100
C12···H15A	2.7900	H112···O2	2.4200
C12···H32Cⁱ	3.0900	H112···N3^v	2.9400
C12···H16A	2.8300	H112···C32ⁱ	3.0200
C12···H15B	3.0800	H112···H32Cⁱ	2.3400
C16···H14B^iv	2.9800

C12—O12—C13	121.10 (18)	C6—C5—H5	120.00
C2—N1—C6	123.04 (19)	N1—C6—H6	120.00
C2—N1—C11	117.79 (18)	C5—C6—H6	120.00
C6—N1—C11	119.00 (19)	N1—C11—H111	109.00
C3—N3—C31	126.7 (2)	N1—C11—H112	109.00
C3—N3—H3	117.00	C12—C11—H111	109.00
C31—N3—H3	117.00	C12—C11—H112	109.00
N1—C2—C3	115.51 (19)	H111—C11—H112	109.00
O2—C2—N1	120.98 (19)	C13—C14—H14A	109.00
O2—C2—C3	123.5 (2)	C13—C14—H14B	109.00
N3—C3—C2	113.04 (19)	C13—C14—H14C	109.00
N3—C3—C4	126.5 (2)	H14A—C14—H14B	110.00
C2—C3—C4	120.5 (2)	H14A—C14—H14C	109.00
C3—C4—C5	120.4 (2)	H14B—C14—H14C	109.00
C4—C5—C6	120.0 (3)	C13—C15—H15A	110.00
N1—C6—C5	120.6 (2)	C13—C15—H15B	109.00
N1—C11—C12	111.23 (19)	C13—C15—H15C	110.00
O11—C12—C11	124.2 (2)	H15A—C15—H15B	109.00
O11—C12—O12	125.7 (2)	H15A—C15—H15C	109.00
O12—C12—C11	110.02 (19)	H15B—C15—H15C	109.00
O12—C13—C15	108.9 (2)	C13—C16—H16A	109.00
O12—C13—C14	103.0 (2)	C13—C16—H16B	109.00
C14—C13—C16	110.8 (3)	C13—C16—H16C	109.00
C15—C13—C16	113.3 (3)	H16A—C16—H16B	109.00
O12—C13—C16	109.9 (2)	H16A—C16—H16C	109.00
C14—C13—C15	110.5 (2)	H16B—C16—H16C	109.00
N3—C31—C32	115.7 (2)	C31—C32—H32A	109.00
O3—C31—N3	122.5 (2)	C31—C32—H32B	109.00
O3—C31—C32	121.8 (2)	C31—C32—H32C	109.00
C3—C4—H4	120.00	H32A—C32—H32B	109.00
C5—C4—H4	120.00	H32A—C32—H32C	109.00
C4—C5—H5	120.00	H32B—C32—H32C	110.00

C13—O12—C12—O11	−5.0 (4)	C31—N3—C3—C4	1.5 (4)
C13—O12—C12—C11	175.59 (19)	C3—N3—C31—O3	1.4 (4)
C12—O12—C13—C14	−177.9 (2)	C3—N3—C31—C32	−179.6 (2)
C12—O12—C13—C15	−60.6 (3)	O2—C2—C3—N3	−1.0 (3)
C12—O12—C13—C16	64.0 (3)	O2—C2—C3—C4	178.7 (2)
C6—N1—C2—O2	−180.0 (2)	N1—C2—C3—N3	178.89 (19)
C6—N1—C2—C3	0.2 (3)	N1—C2—C3—C4	−1.4 (3)
C11—N1—C2—O2	−4.9 (3)	N3—C3—C4—C5	−178.3 (2)
C11—N1—C2—C3	175.25 (19)	C2—C3—C4—C5	2.0 (4)
C2—N1—C6—C5	0.6 (4)	C3—C4—C5—C6	−1.3 (4)
C11—N1—C6—C5	−174.5 (2)	C4—C5—C6—N1	0.0 (4)
C2—N1—C11—C12	−81.1 (2)	N1—C11—C12—O11	11.0 (3)
C6—N1—C11—C12	94.2 (2)	N1—C11—C12—O12	−169.61 (18)
C31—N3—C3—C2	−178.8 (2)

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

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3···O2ⁱ	0.8600	2.3400	3.164 (3)	161.00
C4—H4···O3	0.9500	2.2300	2.830 (3)	120.00
C14—H14A···O3^viii	0.96	2.56	3.465 (4)	157
C15—H15A···O11	0.96	2.44	2.980 (4)	115
C16—H16A···O11	0.96	2.44	2.978 (5)	115
C32—H32C···O2ⁱ	0.96	2.33	3.222 (3)	155

Symmetry codes: (i) −x+2, −y+1, −z; (viii) x−1, y, z.

Experimental details

Crystal data
Chemical formula	C₁₃H₁₈N₂O₄
M_r	266.29
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	295
a, b, c (Å)	13.9417 (15), 5.585 (1), 17.861 (2)
β (°)	97.039 (9)
V (Å³)	1380.3 (3)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.10
Crystal size (mm)	0.40 × 0.30 × 0.20

Data collection
Diffractometer	Rigaku AFC-7R diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	2731, 2428, 1482
R_int	0.046
(sin θ/λ)_max (Å⁻¹)	0.594

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.052, 0.162, 1.02
No. of reflections	2428
No. of parameters	176
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.27, −0.27

Computer programs: MSC/AFC7 Diffractometer Control Software (Molecular Structure Corporation, 1999), TEXSAN for Windows (Molecular Structure Corporation, 2001) and SHELXL97 (Sheldrick, 2008), ORTEP-3 (Farrugia, 1997), TEXSAN for Windows (Molecular Structure Corporation, 2001) and PLATON (Spek, 2003).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3···O2ⁱ	0.8600	2.3400	3.164 (3)	161.00
C4—H4···O3	0.9500	2.2300	2.830 (3)	120.00
C14—H14A···O3ⁱⁱ	0.9600	2.5600	3.465 (4)	157.00
C15—H15A···O11	0.9600	2.4400	2.980 (4)	115.00
C16—H16A···O11	0.9600	2.4400	2.978 (5)	115.00
C32—H32C···O2ⁱ	0.9600	2.3300	3.222 (3)	155.00

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

Acknowledgements

We acknowledge financial support of this work by Griffith University, Eskitis Institute for Cell and Molecular Therapies, Griffith University, and Natural Product Discovery, Griffith University. We also thank Alan White for professional support in this work.

References

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