Nifedipine–pyrazine (2/1)

Schultheiss, N.; Roe, M.; Smit, J.P.

doi:10.1107/S1600536810031703

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 66| Part 9| September 2010| Pages o2297-o2298

https://doi.org/10.1107/S1600536810031703

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Nifedipine–pyrazine (2/1)

Nate Schultheiss,^a ^* Melanie Roe ^a and Jared P. Smit ^a

^aSSCI (a division of Aptuit), 3065 Kent Avenue, West Lafayette, IN 47909, USA
^*Correspondence e-mail: nathan.schultheiss@aptuit.com

(Received 20 July 2010; accepted 6 August 2010; online 11 August 2010)

In the title compound, 2C₁₇H₁₈N₂O₆·C₄H₄N₂ [systematic name: 3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate–pyrazine (2/1)], the complete pyrazine molecule is generated by crystallographic inversion symmetry. The center of the pyrazine ring lies on an inversion center. The nifedipine molecules are linked into chains along the c axis through N—H⋯O hydrogen bonds, while the pyrazine molecules are organized in the structure through van der Waals interactions.

Related literature

Co-crystalline materials are of pharmaceutical interest due to their ability to alter the physicochemical properties of active pharmaceutical ingredients (APIs) (Schultheiss et al., 2009 ) and provide drug repositioning or life-cycle management (Trask, 2007 ). The corresponding crystal structure of nifedipine has been reported (Triggle et al., 2003 ) and it also forms chains through N—H⋯O hydrogen bonds. Other crystalline forms also exist: polymorphs (Burger et al., 1996 ) solvates/hydrates (Caira et al., 2003 ) and a metal complex (Bontchev et al., 2003 ), as well as a non-crystalline, amorphous phase (Miyazaki et al., 2007 ).

Experimental

Crystal data

C₁₉H₂₀N₃O₆
M_r = 386.38
Monoclinic, P 2₁ /c
a = 13.6278 (14) Å
b = 9.1594 (9) Å
c = 14.4432 (14) Å
β = 94.841 (4)°
V = 1796.4 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 120 K
0.24 × 0.18 × 0.10 mm

Data collection

Bruker APEXII CCD diffractometer
27572 measured reflections
6070 independent reflections
4916 reflections with I > 2σ(I)
R_int = 0.036

Refinement

R[F² > 2σ(F²)] = 0.043
wR(F²) = 0.125
S = 1.07
6070 reflections
261 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.48 e Å⁻³
Δρ_min = −0.24 e Å⁻³

Table 1
Selected torsion angles (°)

C12—C13—C14—C31	93.88 (10)
C31—C14—C15—C16	−93.78 (10)

Table 2
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N11—H11⋯O24ⁱ	0.906 (17)	1.942 (17)	2.8444 (12)	173.6 (15)
Symmetry code: (i) $[x, -y+{\script{3\over 2}}, z+{\script{1\over 2}}]$ .

Data collection: APEX2 (Bruker, 2007 ); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009 ); software used to prepare material for publication: SHELXTL (Sheldrick, 2008), PLATON and Mercury (Macrae et al., 2006 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S1600536810031703/kj2152sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536810031703/kj2152Isup2.hkl

checkCIF report

Comment top

Designing, preparing, and characterizing cocrystalline materials is a rapidly growing area of research, especially in the area of pharmaceutics, due to their ability to alter the physicochemical properties of active pharmaceutical ingredients (APIs) (Schultheiss et al., 2009) and provide drug repositioning or life-cycle management (Trask, 2007). Cocrystals are multi-component crystals where the individual, neutral molecules are typically held together through hydrogen-bonding. Nifedipine (1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl) -3,5-pyridine dicarboxylic acid dimethyl ester),a calcium-channel blocker, is known to exist in a variety of crystalline forms: polymorphs (Burger et al., 1996), solvates/hydrates (Caira et al., 2003), and a metal complex (Bontchev et al., 2003), as well as a non-crystalline, amorphous phase (Miyazaki et al., 2007). Suprisingly, examples of nifedipine cocrystals have yet to be published in the open literature, and thus we report here the 2:1 cocrystal of nifedipine and pyrazine.

A view of the asymmetric unit of the title compound and its numbering scheme are displayed in Fig. 1. The material crystallizes in a 2:1 (nifedipine:pyrazine) stoichiometric ratio, although the asymmetric unit contains the components in a 1:0.5 ratio, because the center of the pyrazine ring resides on an inversion center. It should also be noted that the nitro-substituted phenyl ring is relatively orthogonal ("axial") to the dihydropyridine ring (Table 1) which is displayed in Fig. 1. Nonetheless, the nifedipine molecules are linked into linear, one-dimensional chains with a graph set notation of C(6) through N—H···O hydrogen bonds from the N—H moiety to a carbonyl moiety, Table 2. The hydrogen bonds are running along the crystallographic c axis. Interestingly, the pyrazine molecules are not participating in hydrogen bonding with nifedipine, but are organized in between nifedipine rows through multiple van der Waals interactions (Fig. 2). Upon extending the structure into three-dimensions, the organization of the pyrazine molecules within the crystal structure are clearly shown. The pyrazine molecules are not only between one-dimensional rows of nifedipine, but also 'sandwiched' between methyl-ester groups from neighboring nifedipine molecules.

Related literature top

Cocrystalline materials are of pharmaceutical interest due to their ability to alter the physicochemical properties of active pharmaceutical ingredients (APIs) (Schultheiss et al., 2009) and provide drug repositioning or life-cycle management (Trask, 2007). The corresponding crystal structure of nifedipine has been reported (Triggle et al., 2003) and it also forms chains through N—H···O hydrogen bonds. Other crystalline forms also exist: polymorphs (Burger et al., 1996) solvates/hydrates (Caira et al., 2003) and a metal complex (Bontchev et al., 2003), as well as a non-crystalline, amorphous phase (Miyazaki et al., 2007).

Experimental top

The title compound was prepared by adding solid nifedipine to a nearly saturated solution of pyrazine in methanol and allowed to stir for ~24 h at ambient temperature before filtering. Crystals of suitable size for single-crystal analysis were obtained directly from the experiment.

Structure description top

Computing details top

Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: SHELXTL (Sheldrick, 2008), PLATON (Spek, 2009) and Mercury (Macrae et al., 2006).

Figures top

	Fig. 1. The asymmetric unit of the title compound, with the atom labeling scheme and 50% probability displacement ellipsoids.
	Fig. 2. View down the b axis displaying the hydrogen bonding (black-dashed lines) between nifedipine molecules. The pyrazine molecules (ball-and-stick mode) are positioned between the one-dimensional nifedipine rows (right). The direction of the a axis is the red line, the b axis is green, and the c axis is blue.

3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate–pyrazine (2/1) top

Crystal data top

C₁₉H₂₀N₃O₆	F(000) = 812
M_r = 386.38	D_x = 1.429 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 9767 reflections
a = 13.6278 (14) Å	θ = 2.6–31.7°
b = 9.1594 (9) Å	µ = 0.11 mm⁻¹
c = 14.4432 (14) Å	T = 120 K
β = 94.841 (4)°	Prism, colourless
V = 1796.4 (3) Å³	0.24 × 0.18 × 0.10 mm
Z = 4

Data collection top

Bruker APEXII CCD diffractometer	4916 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.036
Graphite monochromator	θ_max = 31.8°, θ_min = 2.6°
φ and ω scans	h = −20→19
27572 measured reflections	k = −13→13
6070 independent reflections	l = −17→21

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)] = 0.043	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.125	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	w = 1/[σ²(F_o²) + (0.070P)² + 0.250P] where P = (F_o² + 2F_c²)/3
6070 reflections	(Δ/σ)_max < 0.001
261 parameters	Δρ_max = 0.48 e Å⁻³
0 restraints	Δρ_min = −0.24 e Å⁻³

Crystal data top

C₁₉H₂₀N₃O₆	V = 1796.4 (3) Å³
M_r = 386.38	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 13.6278 (14) Å	µ = 0.11 mm⁻¹
b = 9.1594 (9) Å	T = 120 K
c = 14.4432 (14) Å	0.24 × 0.18 × 0.10 mm
β = 94.841 (4)°

Data collection top

Bruker APEXII CCD diffractometer	4916 reflections with I > 2σ(I)
27572 measured reflections	R_int = 0.036
6070 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.043	0 restraints
wR(F²) = 0.125	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	Δρ_max = 0.48 e Å⁻³
6070 reflections	Δρ_min = −0.24 e Å⁻³
261 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
N11	0.91012 (7)	0.66064 (10)	0.58015 (6)	0.01904 (17)
H11	0.9275 (12)	0.6672 (17)	0.6420 (12)	0.033 (4)*
C12	0.96337 (7)	0.73800 (11)	0.52067 (6)	0.01680 (18)
C13	0.92963 (7)	0.74418 (11)	0.42914 (6)	0.01588 (17)
C14	0.82937 (7)	0.68380 (10)	0.39640 (6)	0.01536 (17)
H14	0.8323	0.6431	0.3324	0.018*
C15	0.80215 (7)	0.56174 (10)	0.46039 (6)	0.01635 (17)
C16	0.83786 (7)	0.56204 (11)	0.55095 (7)	0.01793 (18)
C22	1.05495 (8)	0.80615 (12)	0.56668 (7)	0.0214 (2)
H22A	1.0559	0.9104	0.5515	0.032*
H22B	1.1129	0.7586	0.5444	0.032*
H22C	1.0558	0.7940	0.6342	0.032*
C23	0.98313 (7)	0.80823 (11)	0.35653 (7)	0.01736 (18)
O23	1.06719 (5)	0.87616 (9)	0.38444 (5)	0.02116 (16)
O24	0.95391 (6)	0.80104 (11)	0.27468 (5)	0.0315 (2)
C25	0.73593 (7)	0.44528 (11)	0.42414 (7)	0.01813 (18)
O25	0.71443 (6)	0.45992 (8)	0.33133 (5)	0.02199 (16)
O26	0.70447 (6)	0.34517 (9)	0.46697 (6)	0.02589 (17)
C26	0.80877 (9)	0.46176 (12)	0.62596 (7)	0.0237 (2)
H26A	0.7373	0.4660	0.6291	0.036*
H26B	0.8418	0.4921	0.6858	0.036*
H26C	0.8282	0.3616	0.6121	0.036*
C27	1.11954 (9)	0.93700 (14)	0.31148 (8)	0.0264 (2)
H27A	1.1818	0.9789	0.3380	0.040*
H27B	1.0795	1.0136	0.2795	0.040*
H27C	1.1330	0.8601	0.2671	0.040*
C28	0.65577 (9)	0.34450 (13)	0.28780 (8)	0.0276 (2)
H28A	0.6401	0.3676	0.2219	0.041*
H28B	0.5946	0.3347	0.3184	0.041*
H28C	0.6926	0.2526	0.2934	0.041*
C31	0.75049 (7)	0.80317 (10)	0.39303 (6)	0.01571 (17)
C32	0.67448 (7)	0.82130 (11)	0.32317 (7)	0.01755 (18)
N32	0.66655 (7)	0.73025 (10)	0.23900 (6)	0.01976 (17)
O32	0.73861 (6)	0.71650 (9)	0.19529 (5)	0.02539 (17)
O33	0.58615 (6)	0.67540 (9)	0.21593 (6)	0.02713 (18)
C33	0.60043 (8)	0.92431 (12)	0.32730 (7)	0.0219 (2)
H33	0.5497	0.9320	0.2782	0.026*
C34	0.60109 (8)	1.01542 (12)	0.40326 (8)	0.0239 (2)
H34	0.5512	1.0872	0.4068	0.029*
C35	0.67529 (8)	1.00121 (12)	0.47455 (7)	0.0227 (2)
H35	0.6763	1.0634	0.5273	0.027*
C36	0.74769 (8)	0.89694 (11)	0.46907 (7)	0.01926 (19)
H36	0.7975	0.8886	0.5189	0.023*
N41	0.45265 (8)	0.46068 (12)	0.41368 (7)	0.0302 (2)
C42	0.45577 (9)	0.37242 (13)	0.48684 (9)	0.0289 (2)
H42	0.4248	0.2796	0.4805	0.035*
C43	0.50253 (9)	0.41122 (14)	0.57190 (8)	0.0297 (2)
H43	0.5027	0.3439	0.6220	0.036*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N11	0.0221 (4)	0.0250 (4)	0.0100 (3)	−0.0011 (3)	0.0008 (3)	0.0011 (3)
C12	0.0176 (4)	0.0209 (4)	0.0119 (4)	0.0010 (3)	0.0011 (3)	−0.0001 (3)
C13	0.0159 (4)	0.0201 (4)	0.0116 (4)	−0.0002 (3)	0.0012 (3)	0.0004 (3)
C14	0.0169 (4)	0.0183 (4)	0.0109 (4)	−0.0003 (3)	0.0015 (3)	−0.0002 (3)
C15	0.0170 (4)	0.0175 (4)	0.0147 (4)	0.0003 (3)	0.0025 (3)	0.0005 (3)
C16	0.0199 (4)	0.0197 (4)	0.0145 (4)	0.0015 (3)	0.0032 (3)	0.0013 (3)
C22	0.0200 (5)	0.0293 (5)	0.0143 (4)	−0.0021 (4)	−0.0014 (3)	−0.0011 (4)
C23	0.0174 (4)	0.0215 (4)	0.0132 (4)	0.0005 (3)	0.0014 (3)	−0.0002 (3)
O23	0.0211 (3)	0.0285 (4)	0.0141 (3)	−0.0065 (3)	0.0031 (3)	−0.0004 (3)
O24	0.0279 (4)	0.0550 (6)	0.0111 (3)	−0.0138 (4)	−0.0004 (3)	0.0043 (3)
C25	0.0182 (4)	0.0187 (4)	0.0178 (4)	0.0024 (3)	0.0029 (3)	−0.0004 (3)
O25	0.0246 (4)	0.0240 (4)	0.0170 (3)	−0.0059 (3)	−0.0004 (3)	−0.0019 (3)
O26	0.0308 (4)	0.0224 (4)	0.0247 (4)	−0.0055 (3)	0.0037 (3)	0.0025 (3)
C26	0.0300 (5)	0.0242 (5)	0.0173 (4)	−0.0007 (4)	0.0043 (4)	0.0057 (4)
C27	0.0270 (5)	0.0335 (6)	0.0196 (5)	−0.0097 (4)	0.0066 (4)	0.0014 (4)
C28	0.0273 (5)	0.0295 (5)	0.0256 (5)	−0.0089 (4)	0.0003 (4)	−0.0067 (4)
C31	0.0166 (4)	0.0175 (4)	0.0131 (4)	−0.0010 (3)	0.0018 (3)	0.0015 (3)
C32	0.0188 (4)	0.0202 (4)	0.0135 (4)	−0.0018 (3)	0.0001 (3)	0.0002 (3)
N32	0.0221 (4)	0.0224 (4)	0.0142 (4)	0.0003 (3)	−0.0022 (3)	0.0010 (3)
O32	0.0270 (4)	0.0339 (4)	0.0155 (3)	0.0015 (3)	0.0033 (3)	−0.0017 (3)
O33	0.0249 (4)	0.0304 (4)	0.0245 (4)	−0.0054 (3)	−0.0067 (3)	−0.0025 (3)
C33	0.0204 (5)	0.0244 (5)	0.0204 (5)	0.0022 (4)	−0.0012 (3)	0.0022 (4)
C34	0.0252 (5)	0.0227 (5)	0.0237 (5)	0.0054 (4)	0.0014 (4)	0.0010 (4)
C35	0.0276 (5)	0.0208 (4)	0.0197 (5)	0.0031 (4)	0.0017 (4)	−0.0029 (4)
C36	0.0223 (5)	0.0204 (4)	0.0149 (4)	0.0009 (3)	0.0002 (3)	−0.0008 (3)
N41	0.0291 (5)	0.0373 (5)	0.0247 (5)	−0.0013 (4)	0.0058 (4)	−0.0037 (4)
C42	0.0283 (6)	0.0271 (5)	0.0327 (6)	−0.0038 (4)	0.0101 (4)	−0.0035 (5)
C43	0.0313 (6)	0.0325 (6)	0.0264 (5)	0.0000 (5)	0.0093 (4)	0.0046 (5)

Geometric parameters (Å, º) top

N11—C12	1.3682 (13)	C27—H27A	0.9800
N11—C16	1.3759 (13)	C27—H27B	0.9800
N11—H11	0.906 (17)	C27—H27C	0.9800
C12—C13	1.3636 (13)	C28—H28A	0.9800
C12—C22	1.4996 (14)	C28—H28B	0.9800
C13—C23	1.4507 (13)	C28—H28C	0.9800
C13—C14	1.5125 (13)	C31—C32	1.3937 (13)
C14—C15	1.5165 (13)	C31—C36	1.3973 (13)
C14—C31	1.5311 (13)	C32—C33	1.3865 (14)
C14—H14	1.0000	C32—N32	1.4706 (13)
C15—C16	1.3566 (13)	N32—O32	1.2180 (12)
C15—C25	1.4651 (14)	N32—O33	1.2257 (12)
C16—C26	1.4989 (14)	C33—C34	1.3778 (15)
C22—H22A	0.9800	C33—H33	0.9500
C22—H22B	0.9800	C34—C35	1.3871 (15)
C22—H22C	0.9800	C34—H34	0.9500
C23—O24	1.2170 (12)	C35—C36	1.3802 (14)
C23—O23	1.3357 (12)	C35—H35	0.9500
O23—C27	1.4342 (12)	C36—H36	0.9500
C25—O26	1.2050 (12)	N41—C42	1.3282 (17)
C25—O25	1.3544 (12)	N41—C43ⁱ	1.3311 (17)
O25—C28	1.4377 (13)	C42—C43	1.3819 (18)
C26—H26A	0.9800	C42—H42	0.9500
C26—H26B	0.9800	C43—N41ⁱ	1.3311 (17)
C26—H26C	0.9800	C43—H43	0.9500

C12—N11—C16	123.46 (8)	O23—C27—H27B	109.5
C12—N11—H11	118.4 (10)	H27A—C27—H27B	109.5
C16—N11—H11	117.8 (10)	O23—C27—H27C	109.5
C13—C12—N11	118.48 (9)	H27A—C27—H27C	109.5
C13—C12—C22	127.75 (9)	H27B—C27—H27C	109.5
N11—C12—C22	113.77 (8)	O25—C28—H28A	109.5
C12—C13—C23	124.66 (9)	O25—C28—H28B	109.5
C12—C13—C14	120.65 (8)	H28A—C28—H28B	109.5
C23—C13—C14	114.68 (8)	O25—C28—H28C	109.5
C13—C14—C15	109.88 (8)	H28A—C28—H28C	109.5
C13—C14—C31	111.23 (8)	H28B—C28—H28C	109.5
C15—C14—C31	109.79 (8)	C32—C31—C36	115.33 (9)
C13—C14—H14	108.6	C32—C31—C14	125.80 (8)
C15—C14—H14	108.6	C36—C31—C14	118.66 (8)
C31—C14—H14	108.6	C33—C32—C31	123.31 (9)
C16—C15—C25	120.41 (9)	C33—C32—N32	114.74 (9)
C16—C15—C14	119.99 (9)	C31—C32—N32	121.95 (9)
C25—C15—C14	119.60 (8)	O32—N32—O33	123.91 (9)
C15—C16—N11	119.08 (9)	O32—N32—C32	118.74 (9)
C15—C16—C26	126.89 (9)	O33—N32—C32	117.32 (9)
N11—C16—C26	114.01 (9)	C34—C33—C32	119.38 (10)
C12—C22—H22A	109.5	C34—C33—H33	120.3
C12—C22—H22B	109.5	C32—C33—H33	120.3
H22A—C22—H22B	109.5	C33—C34—C35	119.32 (10)
C12—C22—H22C	109.5	C33—C34—H34	120.3
H22A—C22—H22C	109.5	C35—C34—H34	120.3
H22B—C22—H22C	109.5	C36—C35—C34	120.14 (10)
O24—C23—O23	121.36 (9)	C36—C35—H35	119.9
O24—C23—C13	122.49 (9)	C34—C35—H35	119.9
O23—C23—C13	116.15 (8)	C35—C36—C31	122.51 (9)
C23—O23—C27	115.24 (8)	C35—C36—H36	118.7
O26—C25—O25	121.79 (9)	C31—C36—H36	118.7
O26—C25—C15	127.27 (9)	C42—N41—C43ⁱ	115.38 (11)
O25—C25—C15	110.91 (8)	C42—N41—C42ⁱⁱ	106.16 (7)
C25—O25—C28	115.21 (8)	C43ⁱ—N41—C42ⁱⁱ	137.11 (8)
C16—C26—H26A	109.5	N41—C42—C43	122.15 (11)
C16—C26—H26B	109.5	N41—C42—H42	118.9
H26A—C26—H26B	109.5	C43—C42—H42	118.9
C16—C26—H26C	109.5	N41ⁱ—C43—C42	122.46 (11)
H26A—C26—H26C	109.5	N41ⁱ—C43—H43	118.8
H26B—C26—H26C	109.5	C42—C43—H43	118.8
O23—C27—H27A	109.5

C16—N11—C12—C13	15.45 (15)	C14—C15—C25—O26	−176.60 (10)
C16—N11—C12—C22	−164.07 (9)	C16—C15—C25—O25	−175.78 (9)
N11—C12—C13—C23	−173.05 (9)	C14—C15—C25—O25	5.23 (12)
C22—C12—C13—C23	6.40 (17)	O26—C25—O25—C28	−2.79 (14)
N11—C12—C13—C14	7.81 (14)	C15—C25—O25—C28	175.50 (8)
C22—C12—C13—C14	−172.75 (9)	C13—C14—C31—C32	138.67 (9)
C12—C13—C14—C15	−27.91 (12)	C15—C14—C31—C32	−99.50 (11)
C23—C13—C14—C15	152.87 (8)	C13—C14—C31—C36	−46.76 (11)
C12—C13—C14—C31	93.88 (10)	C15—C14—C31—C36	75.07 (11)
C23—C13—C14—C31	−85.35 (10)	C36—C31—C32—C33	−0.04 (14)
C13—C14—C15—C16	28.86 (12)	C14—C31—C32—C33	174.69 (9)
C31—C14—C15—C16	−93.78 (10)	C36—C31—C32—N32	−179.46 (9)
C13—C14—C15—C25	−152.15 (8)	C14—C31—C32—N32	−4.73 (15)
C31—C14—C15—C25	85.21 (10)	C33—C32—N32—O32	130.11 (10)
C25—C15—C16—N11	171.13 (9)	C31—C32—N32—O32	−50.42 (13)
C14—C15—C16—N11	−9.89 (14)	C33—C32—N32—O33	−48.13 (12)
C25—C15—C16—C26	−7.30 (15)	C31—C32—N32—O33	131.33 (10)
C14—C15—C16—C26	171.68 (9)	C31—C32—C33—C34	0.63 (16)
C12—N11—C16—C15	−14.39 (15)	N32—C32—C33—C34	−179.91 (9)
C12—N11—C16—C26	164.24 (9)	C32—C33—C34—C35	−0.67 (16)
C12—C13—C23—O24	173.91 (11)	C33—C34—C35—C36	0.14 (17)
C14—C13—C23—O24	−6.90 (14)	C34—C35—C36—C31	0.48 (16)
C12—C13—C23—O23	−6.01 (15)	C32—C31—C36—C35	−0.51 (14)
C14—C13—C23—O23	173.19 (8)	C14—C31—C36—C35	−175.64 (9)
O24—C23—O23—C27	−0.71 (15)	C43ⁱ—N41—C42—C43	−0.10 (19)
C13—C23—O23—C27	179.21 (9)	C42ⁱⁱ—N41—C42—C43	−169.14 (10)
C16—C15—C25—O26	2.38 (16)	N41—C42—C43—N41ⁱ	0.1 (2)

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

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N11—H11···O24ⁱⁱⁱ	0.906 (17)	1.942 (17)	2.8444 (12)	173.6 (15)

Symmetry code: (iii) x, −y+3/2, z+1/2.

Experimental details

Crystal data
Chemical formula	C₁₉H₂₀N₃O₆
M_r	386.38
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	120
a, b, c (Å)	13.6278 (14), 9.1594 (9), 14.4432 (14)
β (°)	94.841 (4)
V (Å³)	1796.4 (3)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.11
Crystal size (mm)	0.24 × 0.18 × 0.10

Data collection
Diffractometer	Bruker APEXII CCD
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	27572, 6070, 4916
R_int	0.036
(sin θ/λ)_max (Å⁻¹)	0.742

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.043, 0.125, 1.07
No. of reflections	6070
No. of parameters	261
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.48, −0.24

Computer programs: APEX2 (Bruker, 2007), SAINT (Bruker, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008), PLATON (Spek, 2009) and Mercury (Macrae et al., 2006).

Selected torsion angles (º) top

C12—C13—C14—C31

93.88 (10)

C31—C14—C15—C16

−93.78 (10)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N11—H11···O24ⁱ	0.906 (17)	1.942 (17)	2.8444 (12)	173.6 (15)

Symmetry code: (i) x, −y+3/2, z+1/2.

Acknowledgements

We would like to thank Dr John Desper (Kansas State Univeristy) for the data collection and structure solution. We also thank Mr Eyal Barash and Dr Richard McClurg for their careful review of this manuscript.

References

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