Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270113021781/qs3028sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270113021781/qs3028Isup2.hkl | |
Chemical Markup Language (CML) file https://doi.org/10.1107/S0108270113021781/qs3028Isup3.cml |
CCDC reference: 900739
The use of gabapentin [(1-aminomethyl)cyclohexaneacetic acid, Gpn] as a γ-amino acid is of great interest in the area of peptide design (Ananda et al., 2003; Vasudev et al., 2007; Balaram, 2010). Gabapentin has been used widely as an antiepileptic drug and has been employed for the treatment of neuropathic pain (Wheeler, 2002; Stefan & Feuerstein, 2007; Rosenberg et al., 1997; Maneuf et al., 2003). It has been extensively investigated for the occurrence of polymorphic crystal forms (Ibers, 2001; Reece & Levendis, 2008). The insertion of additional residues into the α-peptide backbone by the introduction of β-, γ- and higher ω-amino acids leads to greater conformational diversity due to the enhanced conformational space. There are four conformational variables, i.e. φ, θ1, θ2 and ψ for a γ-amino acid (Fig. 1). The presence of substituents at the central Cβ atom of gabapentin limits the range of conformations about the Cγ—Cβ (θ1) and Cβ—Cα (θ2) bonds to the gauche conformation (Ananda et al., 2003; Aravinda, Ananda et al., 2003). In the present study, we have synthesized the N-protected pyrazinoyl derivative of gabapentin, namely 2-{1-[(pyrazin-2-ylformamido)methyl]cyclohexyl}acetic acid, Pyr-Gpn-OH, in order to investigate the effect of the pyrazinoyl group on the conformation of gabapentin. The pyrazinoyl group has been introduced as an N-terminal protecting group of borteozomib, a reversible inhibitor of the proteolytic activity of 26S proteasome (Voorhees & Orlowski, 2006; Baker et al., 2009). Previous studies have shown that the amide of pyrazinoic acid, i.e. pyrazinamide, is used as a first-line drug to treat tuberculosis (Snider & Castro, 1998). Under acidic conditions it is thought to be a prodrug of pyrazinoic acid, which is a compound with antimycobacterial activity (Cyanamon et al., 1992).
For the synthesis of Pyr-Gpn-OH, pyrazine-2-carboxylic acid (3 mmol, 372 mg) was dissolved in dry CH2Cl2 [Quantity?] and N-methylmorpholine (200 µl) was added, followed by Gpn-OMe.HCl (3 mmol, 666.5 mg) and EDCI.HCl (Define?; 3 mmol, 576 mg) under ice-cold conditions. The reaction mixture was stirred at room temperature for 12 h. After completion of the reaction, water was added [Quantity?] and then the reaction mixture was extracted with CH2Cl2 (3 × 5 ml). The combined organic layer was washed with 2 N HCl (2 × 5 ml), Na2CO3 (2 × 5 ml) and brine (2 × 5 ml). The organic layer was passed over anhydrous Na2SO4 and evaporated to give Pyr-Gpn-OMe (yield 610 mg, 69.8%).
Pyr-Gpn-OMe (2 mmol, 580 mg) was dissolved in methanol (2 ml) and 2 N NaOH (1 ml), and the reaction mixture stirred at room temperature for 4 h. The methanol was evaporated off and the residue extracted with diethyl ether (2 × 5 ml). The aqueous layer was acidified with 2N HCl and extracted with ethyl acetate (3 × 5 ml). The combined organic layer was washed with brine solution (1 × 5 ml). The ethyl acetate layer was passed over anhydrous Na2SO4 and evaporated to give Pyr-Gpn-OH (yield 380 mg, 69.0%). [Comment states Pyr-Gpn-OH was crystallized by slow evaporation from a mixture of ethyl acetate–hexane. Therefore, please complete procedure here. Solvent ratio?]
Crystal data, data collection and structure refinement details are summarized in Table 1. H atoms were located in a difference Fourier map and their coordinates restrained to geometric positions; their displacement parameters were restrained to a value 20% greater than the parent atom.
The compound Pyr-Gpn-OH was crystallized by slow evaporation from a mixture of ethyl acetate–hexane [Solvent ratio?] in the triclinic space group P1. In most cases, N-protected derivatives of gabapentin crystallize in monoclininic space groups (Ananda et al., 2003). Fig. 2 shows the molecular conformation determined for the crystal structure of Pyr-Gpn-OH. The backbone dihedral angles are φ = 93.3 (2)°, θ1 = 43.5 (2)°, θ2 = 55.9 (2)° and ψ = 116.4 (2)°. Hydrogen-bond parameters are listed in Table 2.
In the crystal structure, five- (C5) and seven-membered (C7) intramolecular hydrogen bonds are present. The C5 (N—H···N) intramolecular hydrogen bond is observed between atom N2 of the pyrazine ring and the NH group of gabapentin, while the C7 (N—H···O) hydrogen bond is observed between GpnNH and the carbonyl group of the terminal carboxylic acid group. The C7 hydrogen bond in gabapentin may be considered as an expansion of C5 hydrogen-bonded structures described in fully extended conformations of α-peptides (Benedetti et al., 1984, 1988; Valle et al., 1986). In addition to the C5 and C7 hydrogen bonds, a weak C—H···O interaction is also observed between Gpn CγH and Pyr CO groups. These kinds of interactions are important determinants of molecular conformation and crystal packing (Desiraju, 1996; Steiner, 1997; Lo Prestil et al., 2006).
The dihedral angles about the Cγ—Cβ (θ1) and Cβ—Cα (θ2) bonds are restricted to the gauche conformation due to the presence of substituents at the Cβ atom, which limits the range of rotation. The cyclohexane ring adopts a chair conformation, with axial amino methyl and equatorial carboxymethyl groups, as observed in derivatives of gabapentin, Piv-Gpn-OH and Tos-Gpn-OH (Ananda et al., 2003). In Pyr-Gpn-OH, the N-terminal protecting group favours a trans geometry with ω0 = -175.1 (2)°.
Fig. 3 shows the packing of the molecules of Pyr-Gpn-OH in the crystal structure, down the a axis. The molecules are arranged via O—H···.O and C—H···N (pyrazine N atom) intermolecular hydrogen bonds, together with π–π interactions between the pyrazine rings, which are stacked in a face-to-face (3.76 Å) and edge-to-face (6.04 Å) manner (Fig. 3). π–π interactions have been reported to induce self-assembly in peptides (Ma et al., 2010; Wang & Chau, 2011). The distances between the centroids of the pyrazine rings are within the range for stabilizing π–π interactions (Burley & Petsko, 1985; Waters, 2002; Aravinda, Shamala et al., 2003; Sengupta et al., 2005). Fig. 4 shows a space-filling model for the structure of Pyr-Gpn-OH, and depicts the layers formed by alternating π–π and hydrophobic interactions.
The present X-ray analysis of Pyr-Gpn-OH demonstrates the stabilization of the crystal structure by C5, C7 and C—H···O intramolecular hydrogen bonds. The molecules in the crystal are packed by intermolecular O—H···O and C—H···N hydrogen bonds, together with π–π interactions between pyrazine rings.
Data collection: CrysAlis PRO (Oxford Diffraction, 2010); cell refinement: CrysAlis PRO (Oxford Diffraction, 2010); data reduction: CrysAlis PRO (Oxford Diffraction, 2010); 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, 2012); software used to prepare material for publication: PLATON (Spek, 2009).
C14H19N3O3 | Z = 2 |
Mr = 277.32 | F(000) = 296 |
Triclinic, P1 | Dx = 1.288 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 7.7253 (4) Å | Cell parameters from 3944 reflections |
b = 8.6778 (5) Å | θ = 3.6–28.0° |
c = 11.5759 (7) Å | µ = 0.09 mm−1 |
α = 72.136 (5)° | T = 293 K |
β = 87.590 (4)° | Rod, colourless |
γ = 75.671 (4)° | 0.41 × 0.15 × 0.10 mm |
V = 715.16 (7) Å3 |
Oxford Xcalibur Sapphire3 diffractometer | 3326 independent reflections |
Radiation source: fine-focus sealed tube | 2048 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.033 |
Detector resolution: 16.1049 pixels mm-1 | θmax = 28.0°, θmin = 3.6° |
ω scans | h = −10→10 |
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2010) | k = −11→11 |
Tmin = 0.986, Tmax = 1.000 | l = −15→15 |
12592 measured reflections |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.050 | All H-atom parameters refined |
wR(F2) = 0.161 | w = 1/[σ2(Fo2) + (0.0805P)2 + 0.0541P] where P = (Fo2 + 2Fc2)/3 |
S = 1.01 | (Δ/σ)max < 0.001 |
3326 reflections | Δρmax = 0.18 e Å−3 |
258 parameters | Δρmin = −0.15 e Å−3 |
0 restraints | Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.025 (5) |
C14H19N3O3 | γ = 75.671 (4)° |
Mr = 277.32 | V = 715.16 (7) Å3 |
Triclinic, P1 | Z = 2 |
a = 7.7253 (4) Å | Mo Kα radiation |
b = 8.6778 (5) Å | µ = 0.09 mm−1 |
c = 11.5759 (7) Å | T = 293 K |
α = 72.136 (5)° | 0.41 × 0.15 × 0.10 mm |
β = 87.590 (4)° |
Oxford Xcalibur Sapphire3 diffractometer | 3326 independent reflections |
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2010) | 2048 reflections with I > 2σ(I) |
Tmin = 0.986, Tmax = 1.000 | Rint = 0.033 |
12592 measured reflections |
R[F2 > 2σ(F2)] = 0.050 | 0 restraints |
wR(F2) = 0.161 | All H-atom parameters refined |
S = 1.01 | Δρmax = 0.18 e Å−3 |
3326 reflections | Δρmin = −0.15 e Å−3 |
258 parameters |
Experimental. CrysAlis PRO, Oxford Diffraction Ltd., Version 1.171.34.40 (release 27–08-2010 CrysAlis171. NET) (compiled Aug 27 2010,11:50:40) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm. |
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. |
x | y | z | Uiso*/Ueq | ||
H1G | 0.686 (2) | 0.488 (2) | 0.1769 (16) | 0.058 (5)* | |
H1N | 0.355 (3) | 0.457 (3) | 0.1255 (19) | 0.073 (6)* | |
H2B | 0.627 (3) | 0.306 (3) | 0.492 (2) | 0.083 (7)* | |
H5 | 0.131 (3) | 0.911 (3) | 0.1984 (19) | 0.068 (6)* | |
H2G | 0.658 (2) | 0.341 (2) | 0.1307 (17) | 0.058 (5)* | |
H2 | −0.139 (3) | 0.650 (3) | −0.0047 (19) | 0.077 (6)* | |
H1A | 0.371 (3) | 0.281 (3) | 0.342 (2) | 0.078 (7)* | |
H4B | 0.829 (3) | 0.102 (3) | 0.2722 (19) | 0.068 (6)* | |
H2A | 0.511 (3) | 0.122 (3) | 0.427 (2) | 0.080 (7)* | |
H1B | 0.515 (3) | 0.476 (3) | 0.3923 (17) | 0.062 (5)* | |
H3 | −0.304 (3) | 0.896 (3) | 0.050 (2) | 0.085 (7)* | |
H6G | 1.080 (4) | 0.148 (3) | 0.346 (2) | 0.101 (8)* | |
H5G | 0.980 (4) | 0.305 (4) | 0.247 (3) | 0.124 (13)* | |
H4G | 0.777 (3) | 0.507 (3) | 0.471 (2) | 0.087 (7)* | |
H3B | 0.823 (3) | 0.066 (3) | 0.421 (3) | 0.104 (9)* | |
H1D | 1.060 (4) | 0.380 (4) | 0.412 (3) | 0.129 (11)* | |
H1M | 0.483 (4) | −0.116 (4) | 0.260 (3) | 0.120 (10)* | |
H3G | 0.785 (4) | 0.556 (4) | 0.318 (3) | 0.118 (10)* | |
H2D | 0.965 (4) | 0.242 (4) | 0.501 (3) | 0.113 (13)* | |
N2 | 0.0902 (2) | 0.64318 (19) | 0.07084 (14) | 0.0555 (4) | |
C2 | −0.0822 (3) | 0.7087 (3) | 0.04216 (19) | 0.0610 (5) | |
C3 | −0.1777 (3) | 0.8475 (3) | 0.0709 (2) | 0.0676 (6) | |
N3 | −0.1018 (3) | 0.9239 (2) | 0.13047 (18) | 0.0770 (6) | |
C5 | 0.0719 (3) | 0.8599 (3) | 0.1575 (2) | 0.0676 (6) | |
C6 | 0.1689 (2) | 0.7219 (2) | 0.12800 (16) | 0.0507 (5) | |
C0' | 0.3641 (3) | 0.6548 (2) | 0.15965 (16) | 0.0526 (5) | |
O0 | 0.45127 (19) | 0.73629 (17) | 0.19233 (15) | 0.0750 (5) | |
N1 | 0.4342 (2) | 0.50270 (18) | 0.15107 (13) | 0.0512 (4) | |
C1G | 0.6165 (3) | 0.4068 (3) | 0.18565 (17) | 0.0522 (5) | |
C1B | 0.6390 (2) | 0.2881 (2) | 0.31614 (15) | 0.0463 (4) | |
C1A | 0.4881 (3) | 0.1961 (3) | 0.34526 (18) | 0.0556 (5) | |
C1' | 0.4672 (2) | 0.0999 (2) | 0.26079 (18) | 0.0535 (5) | |
O1 | 0.4980 (2) | −0.06169 (17) | 0.31539 (14) | 0.0766 (5) | |
O2 | 0.4235 (2) | 0.16177 (18) | 0.15526 (14) | 0.0800 (5) | |
C1B1 | 0.6297 (3) | 0.3843 (3) | 0.4090 (2) | 0.0579 (5) | |
C1G1 | 0.7878 (3) | 0.4591 (4) | 0.4060 (3) | 0.0856 (9) | |
C1D | 0.9640 (4) | 0.3269 (6) | 0.4232 (5) | 0.1135 (13) | |
C1G2 | 0.9768 (3) | 0.2346 (5) | 0.3296 (4) | 0.1009 (12) | |
C1B2 | 0.8196 (3) | 0.1594 (3) | 0.3335 (3) | 0.0713 (7) |
U11 | U22 | U33 | U12 | U13 | U23 | |
N2 | 0.0678 (11) | 0.0495 (9) | 0.0588 (9) | −0.0233 (8) | 0.0016 (8) | −0.0230 (8) |
C2 | 0.0650 (13) | 0.0623 (12) | 0.0664 (13) | −0.0266 (11) | 0.0017 (10) | −0.0261 (11) |
C3 | 0.0637 (14) | 0.0751 (15) | 0.0705 (14) | −0.0211 (12) | 0.0061 (11) | −0.0288 (12) |
N3 | 0.0736 (13) | 0.0793 (13) | 0.0879 (13) | −0.0074 (10) | −0.0007 (10) | −0.0483 (11) |
C5 | 0.0757 (15) | 0.0648 (13) | 0.0757 (14) | −0.0161 (11) | −0.0057 (11) | −0.0406 (12) |
C6 | 0.0682 (12) | 0.0413 (9) | 0.0484 (10) | −0.0199 (9) | 0.0012 (8) | −0.0169 (8) |
C0' | 0.0694 (12) | 0.0426 (10) | 0.0535 (10) | −0.0224 (9) | 0.0011 (9) | −0.0187 (8) |
O0 | 0.0791 (10) | 0.0548 (8) | 0.1081 (12) | −0.0284 (7) | −0.0078 (8) | −0.0386 (8) |
N1 | 0.0608 (10) | 0.0456 (9) | 0.0545 (9) | −0.0180 (8) | −0.0039 (7) | −0.0213 (7) |
C1G | 0.0557 (11) | 0.0587 (11) | 0.0546 (11) | −0.0218 (10) | 0.0137 (9) | −0.0305 (10) |
C1B | 0.0481 (9) | 0.0506 (10) | 0.0504 (10) | −0.0115 (8) | 0.0018 (7) | −0.0309 (8) |
C1A | 0.0754 (14) | 0.0515 (11) | 0.0498 (12) | −0.0268 (11) | 0.0066 (10) | −0.0213 (10) |
C1' | 0.0599 (11) | 0.0471 (10) | 0.0624 (12) | −0.0201 (9) | −0.0019 (9) | −0.0231 (9) |
O1 | 0.1225 (13) | 0.0489 (8) | 0.0686 (10) | −0.0361 (9) | −0.0017 (8) | −0.0203 (7) |
O2 | 0.1212 (13) | 0.0572 (9) | 0.0672 (10) | −0.0219 (9) | −0.0310 (9) | −0.0226 (8) |
C1B1 | 0.0643 (13) | 0.0654 (13) | 0.0600 (13) | −0.0169 (11) | 0.0028 (10) | −0.0413 (11) |
C1G1 | 0.0698 (15) | 0.113 (2) | 0.116 (2) | −0.0320 (14) | 0.0060 (14) | −0.087 (2) |
C1D | 0.0646 (17) | 0.158 (3) | 0.161 (4) | −0.024 (2) | −0.0146 (19) | −0.111 (3) |
C1G2 | 0.0474 (14) | 0.138 (3) | 0.148 (3) | −0.0034 (16) | −0.0053 (16) | −0.101 (3) |
C1B2 | 0.0628 (13) | 0.0753 (15) | 0.0874 (17) | 0.0008 (11) | −0.0115 (11) | −0.0538 (15) |
N2—C2 | 1.325 (3) | C1A—C1' | 1.503 (2) |
N2—C6 | 1.338 (2) | C1A—H1A | 1.01 (2) |
C2—C3 | 1.375 (3) | C1A—H2A | 0.96 (2) |
C2—H2 | 1.02 (2) | C1'—O2 | 1.199 (2) |
C3—N3 | 1.329 (3) | C1'—O1 | 1.314 (2) |
C3—H3 | 0.97 (2) | O1—H1M | 0.93 (3) |
N3—C5 | 1.330 (3) | C1B1—C1G1 | 1.513 (3) |
C5—C6 | 1.378 (3) | C1B1—H2B | 0.99 (2) |
C5—H5 | 0.94 (2) | C1B1—H1B | 1.01 (2) |
C6—C0' | 1.492 (3) | C1G1—C1D | 1.523 (4) |
C0'—O0 | 1.232 (2) | C1G1—H4G | 0.96 (2) |
C0'—N1 | 1.329 (2) | C1G1—H3G | 1.10 (3) |
N1—C1G | 1.449 (2) | C1D—C1G2 | 1.519 (4) |
N1—H1N | 0.91 (2) | C1D—H1D | 0.95 (3) |
C1G—C1B | 1.533 (3) | C1D—H2D | 0.97 (3) |
C1G—H1G | 0.968 (19) | C1G2—C1B2 | 1.508 (4) |
C1G—H2G | 0.975 (19) | C1G2—H6G | 0.93 (3) |
C1B—C1B2 | 1.532 (3) | C1G2—H5G | 0.97 (3) |
C1B—C1B1 | 1.540 (2) | C1B2—H4B | 0.97 (2) |
C1B—C1A | 1.540 (2) | C1B2—H3B | 1.08 (3) |
C2—N2—C6 | 116.12 (16) | C1B—C1A—H2A | 107.3 (13) |
N2—C2—C3 | 122.69 (19) | H1A—C1A—H2A | 108.4 (17) |
N2—C2—H2 | 115.1 (12) | O2—C1'—O1 | 122.56 (17) |
C3—C2—H2 | 122.2 (12) | O2—C1'—C1A | 124.60 (18) |
N3—C3—C2 | 121.6 (2) | O1—C1'—C1A | 112.82 (18) |
N3—C3—H3 | 115.9 (13) | C1'—O1—H1M | 109.9 (18) |
C2—C3—H3 | 122.5 (13) | C1G1—C1B1—C1B | 113.19 (17) |
C3—N3—C5 | 115.73 (19) | C1G1—C1B1—H2B | 108.2 (13) |
N3—C5—C6 | 122.96 (19) | C1B—C1B1—H2B | 108.4 (13) |
N3—C5—H5 | 118.6 (12) | C1G1—C1B1—H1B | 109.5 (11) |
C6—C5—H5 | 118.4 (12) | C1B—C1B1—H1B | 108.6 (11) |
N2—C6—C5 | 120.85 (19) | H2B—C1B1—H1B | 108.8 (17) |
N2—C6—C0' | 118.04 (15) | C1B1—C1G1—C1D | 111.5 (3) |
C5—C6—C0' | 121.11 (16) | C1B1—C1G1—H4G | 107.8 (14) |
O0—C0'—N1 | 123.34 (18) | C1D—C1G1—H4G | 109.1 (14) |
O0—C0'—C6 | 121.32 (16) | C1B1—C1G1—H3G | 109.0 (15) |
N1—C0'—C6 | 115.34 (15) | C1D—C1G1—H3G | 109.3 (15) |
C0'—N1—C1G | 125.42 (16) | H4G—C1G1—H3G | 110 (2) |
C0'—N1—H1N | 114.4 (13) | C1G2—C1D—C1G1 | 110.5 (2) |
C1G—N1—H1N | 120.0 (13) | C1G2—C1D—H1D | 108 (2) |
N1—C1G—C1B | 113.67 (14) | C1G1—C1D—H1D | 109 (2) |
N1—C1G—H1G | 105.9 (11) | C1G2—C1D—H2D | 105 (2) |
C1B—C1G—H1G | 109.7 (11) | C1G1—C1D—H2D | 108.5 (19) |
N1—C1G—H2G | 109.3 (11) | H1D—C1D—H2D | 116 (3) |
C1B—C1G—H2G | 108.3 (11) | C1B2—C1G2—C1D | 111.5 (3) |
H1G—C1G—H2G | 110.0 (15) | C1B2—C1G2—H6G | 107.6 (16) |
C1B2—C1B—C1G | 109.94 (16) | C1D—C1G2—H6G | 109.6 (16) |
C1B2—C1B—C1B1 | 108.88 (15) | C1B2—C1G2—H5G | 106.4 (19) |
C1G—C1B—C1B1 | 111.26 (15) | C1D—C1G2—H5G | 113 (2) |
C1B2—C1B—C1A | 109.17 (17) | H6G—C1G2—H5G | 108 (2) |
C1G—C1B—C1A | 110.92 (14) | C1G2—C1B2—C1B | 113.2 (2) |
C1B1—C1B—C1A | 106.58 (14) | C1G2—C1B2—H4B | 110.6 (12) |
C1'—C1A—C1B | 115.47 (15) | C1B—C1B2—H4B | 109.2 (12) |
C1'—C1A—H1A | 107.4 (12) | C1G2—C1B2—H3B | 108.5 (14) |
C1B—C1A—H1A | 108.4 (12) | C1B—C1B2—H3B | 108.4 (14) |
C1'—C1A—H2A | 109.6 (13) | H4B—C1B2—H3B | 106.8 (18) |
C6—N2—C2—C3 | −1.2 (3) | N1—C1G—C1B—C1A | 43.51 (19) |
N2—C2—C3—N3 | −0.5 (3) | C1B2—C1B—C1A—C1' | −65.4 (2) |
C2—C3—N3—C5 | 1.5 (3) | C1G—C1B—C1A—C1' | 55.9 (2) |
C3—N3—C5—C6 | −0.9 (3) | C1B1—C1B—C1A—C1' | 177.17 (18) |
C2—N2—C6—C5 | 1.9 (3) | C1B—C1A—C1'—O2 | −65.2 (3) |
C2—N2—C6—C0' | −178.66 (16) | C1B—C1A—C1'—O1 | 116.4 (2) |
N3—C5—C6—N2 | −0.9 (3) | C1B2—C1B—C1B1—C1G1 | 53.0 (3) |
N3—C5—C6—C0' | 179.67 (19) | C1G—C1B—C1B1—C1G1 | −68.3 (2) |
N2—C6—C0'—O0 | 167.00 (17) | C1A—C1B—C1B1—C1G1 | 170.6 (2) |
C5—C6—C0'—O0 | −13.5 (3) | C1B—C1B1—C1G1—C1D | −55.2 (3) |
N2—C6—C0'—N1 | −13.6 (2) | C1B1—C1G1—C1D—C1G2 | 55.1 (5) |
C5—C6—C0'—N1 | 165.85 (18) | C1G1—C1D—C1G2—C1B2 | −55.6 (5) |
O0—C0'—N1—C1G | 4.3 (3) | C1D—C1G2—C1B2—C1B | 56.3 (4) |
C6—C0'—N1—C1G | −175.07 (15) | C1G—C1B—C1B2—C1G2 | 68.7 (3) |
C0'—N1—C1G—C1B | 93.3 (2) | C1B1—C1B—C1B2—C1G2 | −53.4 (3) |
N1—C1G—C1B—C1B2 | 164.35 (15) | C1A—C1B—C1B2—C1G2 | −169.4 (2) |
N1—C1G—C1B—C1B1 | −74.95 (18) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1N···O2 | 0.91 (2) | 2.40 (3) | 2.965 (2) | 120.2 (19) |
N1—H1N···N2 | 0.91 (2) | 2.25 (2) | 2.707 (2) | 111 (2) |
C1G—H1G···O0 | 0.96 (2) | 2.49 (2) | 2.852 (3) | 102.0 (15) |
O1—H1M···O0i | 0.94 (3) | 1.75 (3) | 2.670 (2) | 165 (3) |
C1B2—H4B···N3ii | 0.97 (2) | 2.54 (2) | 3.503 (4) | 171.0 (19) |
Symmetry codes: (i) x, y−1, z; (ii) x+1, y−1, z. |
Experimental details
Crystal data | |
Chemical formula | C14H19N3O3 |
Mr | 277.32 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 293 |
a, b, c (Å) | 7.7253 (4), 8.6778 (5), 11.5759 (7) |
α, β, γ (°) | 72.136 (5), 87.590 (4), 75.671 (4) |
V (Å3) | 715.16 (7) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.41 × 0.15 × 0.10 |
Data collection | |
Diffractometer | Oxford Xcalibur Sapphire3 diffractometer |
Absorption correction | Multi-scan (CrysAlis PRO; Oxford Diffraction, 2010) |
Tmin, Tmax | 0.986, 1.000 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 12592, 3326, 2048 |
Rint | 0.033 |
(sin θ/λ)max (Å−1) | 0.661 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.050, 0.161, 1.01 |
No. of reflections | 3326 |
No. of parameters | 258 |
H-atom treatment | All H-atom parameters refined |
Δρmax, Δρmin (e Å−3) | 0.18, −0.15 |
Computer programs: CrysAlis PRO (Oxford Diffraction, 2010), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 2012), PLATON (Spek, 2009).
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1N···O2 | 0.91 (2) | 2.40 (3) | 2.965 (2) | 120.2 (19) |
N1—H1N···N2 | 0.91 (2) | 2.25 (2) | 2.707 (2) | 111 (2) |
C1G—H1G···O0 | 0.96 (2) | 2.49 (2) | 2.852 (3) | 102.0 (15) |
O1—H1M···O0i | 0.94 (3) | 1.75 (3) | 2.670 (2) | 165 (3) |
C1B2—H4B···N3ii | 0.97 (2) | 2.54 (2) | 3.503 (4) | 171.0 (19) |
Symmetry codes: (i) x, y−1, z; (ii) x+1, y−1, z. |