organic compounds
Paliperidonium nitrate
aSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China, and bCollege of Chemistry and Chemical Engineering, Southeast University, Nanjing 210096, People's Republic of China
*Correspondence e-mail: jingshui03@163.com
In the title molecular salt (systematic name: 3-{2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl}-9-hydroxy-2-methyl-1,6,7,8,9,9a-hexahydropyrido[1,2-a]pyrimidin-4-one nitrate), C23H29FN4O3+·NO3−, the piperidine ring displays a chair conformation and its N atom is protonated; the N—H bond is in an axial orientation. The ring bearing the hydroxy group exhibits a half-chair conformation. The hydroxy group as well as the adjacent methylene group are disordered over two sets of sites in a 0.823 (5):0.177 (5) ratio. In the crystal, O—H⋯N, O—H⋯O, N—H⋯O and N—H⋯N hydrogen bonds connect the components into a three-dimensional network.
Related literature
For et al. (2012). For background to the anti-psychotic drug paliperidone, see: Spina & Crupi (2011).
of pharmaceutical materials, see: LuoExperimental
Crystal data
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Refinement
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Data collection: CrystalClear (Rigaku, 2005); cell CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg & Putz, 2005); software used to prepare material for publication: SHELXL97.
Supporting information
https://doi.org/10.1107/S160053681203841X/hb6895sup1.cif
contains datablocks I, New_Global_Publ_Block. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S160053681203841X/hb6895Isup2.hkl
The title compound are provided by Changzhou Siyao Pharmaceuticals Co. Ltd (Changzhou, China). Yellow blocks were obstained by slow evaporation of a methanol solution.
All H atoms attached to C atoms, N atoms and O atoms were fixed geometrically and treated as riding with C—H = 0.93 Å (CH), C—H = 0.97 Å (CH2), C—H = 0.96 Å (CH3), N—H = 0.86 Å and O—H = 0.82 Å with Uiso(H) =1.2Ueq(CH, CH2 and NH) and Uiso(H) = 1.5Ueq(CH3 and OH).
In recent years, the studies of
for pharmaceutical ingredients have received much attention, different polymorphs can affect shelf life,durability, solubility, as well as bioavailability and manufacturing of a drug (Luo et al.,2012). Paliperidone or 9-hydroxyrisperidone, is one of the most recently available atypical antipsychotics (Spina & Crupi, 2011). It is a benzisoxazole derivative and the major active metabolite of risperidone, a widely used atypical antipsychotic approved for the treatment of schizophrenia and other psychiatric disorders. In view of the importance of the polymorphs of paliperidone, we reported here a pesudo-polymorphism of paliperidone: paliperidonium nitrate.The
of the title compound consisting of a paliperidone cation and a nitrate ion (Fig. 1) The piperidine ring of the paliperidone cation displays a chair conformation with the nitrogen atoms charged with a hydrion, while the ring which bears the hydroxy group exhibits a half-chair conformation. The hydroxy group as well as the neighbour carbon atom (C21), are disordered over two positions, both with site occupancy factors of 0.82263 and 0.17737.In the crystal, inteicate classical O—H···N, O—H···O, N—H···O and N—H···N hydrogen bonds between the paliperidone cation and the nitrate ion are observed, which connect the molecules into complex structure.(Fig. 2).
For
of pharmaceutical materials, see: Luo et al. (2012). For background to the anti-psychotic drug paliperidone, see: Spina & Crupi (2011).Data collection: CrystalClear (Rigaku, 2005); cell
CrystalClear (Rigaku, 2005); data reduction: CrystalClear (Rigaku, 2005); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg & Putz, 2005); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).Fig. 1. The molecular structure of the title compound with displacement ellipsoids drawn at the 30% probability level. | |
Fig. 2. A packing view showing the three dimensionnal network. Intermolecular hydrogen bonds are shown as dashed lines. |
C23H29FN4O3+·NO3− | F(000) = 1036 |
Mr = 490.51 | Dx = 1.421 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71075 Å |
Hall symbol: -P 2ybc | Cell parameters from 5234 reflections |
a = 8.3642 (8) Å | θ = 3.0–27.5° |
b = 22.032 (2) Å | µ = 0.11 mm−1 |
c = 12.4485 (13) Å | T = 293 K |
β = 92.311 (3)° | Block, yellow |
V = 2292.1 (4) Å3 | 0.30 × 0.25 × 0.24 mm |
Z = 4 |
Rigaku SCXmini diffractometer | 5234 independent reflections |
Radiation source: fine-focus sealed tube | 2824 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.063 |
Detector resolution: 13.6612 pixels mm-1 | θmax = 27.5°, θmin = 3.0° |
CCD_Profile_fitting scans | h = −10→10 |
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005) | k = −28→28 |
Tmin = 0.968, Tmax = 0.974 | l = −16→16 |
23571 measured reflections |
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)] = 0.063 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.178 | H-atom parameters constrained |
S = 1.06 | w = 1/[σ2(Fo2) + (0.0748P)2 + 0.3819P] where P = (Fo2 + 2Fc2)/3 |
5234 reflections | (Δ/σ)max = 0.003 |
353 parameters | Δρmax = 0.42 e Å−3 |
0 restraints | Δρmin = −0.45 e Å−3 |
C23H29FN4O3+·NO3− | V = 2292.1 (4) Å3 |
Mr = 490.51 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 8.3642 (8) Å | µ = 0.11 mm−1 |
b = 22.032 (2) Å | T = 293 K |
c = 12.4485 (13) Å | 0.30 × 0.25 × 0.24 mm |
β = 92.311 (3)° |
Rigaku SCXmini diffractometer | 5234 independent reflections |
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005) | 2824 reflections with I > 2σ(I) |
Tmin = 0.968, Tmax = 0.974 | Rint = 0.063 |
23571 measured reflections |
R[F2 > 2σ(F2)] = 0.063 | 0 restraints |
wR(F2) = 0.178 | H-atom parameters constrained |
S = 1.06 | Δρmax = 0.42 e Å−3 |
5234 reflections | Δρmin = −0.45 e Å−3 |
353 parameters |
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 | Occ. (<1) | |
F1 | 0.0565 (2) | 0.98896 (7) | 0.73885 (17) | 0.0799 (6) | |
O1 | 0.2639 (2) | 0.84040 (8) | 0.50551 (14) | 0.0536 (5) | |
O2 | 0.2927 (3) | 0.47739 (9) | 0.97215 (18) | 0.0750 (7) | |
N1 | 0.2679 (3) | 0.77565 (10) | 0.51391 (17) | 0.0492 (6) | |
N2 | 0.3289 (2) | 0.57545 (8) | 0.67565 (15) | 0.0362 (5) | |
H2 | 0.4299 | 0.5821 | 0.6536 | 0.043* | |
N3 | 0.2952 (2) | 0.37405 (9) | 0.97199 (16) | 0.0424 (5) | |
N4 | 0.4064 (3) | 0.32060 (9) | 0.83226 (17) | 0.0457 (5) | |
H4A | 0.4284 | 0.2865 | 0.8028 | 0.055* | |
C1 | 0.1967 (3) | 0.76100 (11) | 0.60118 (18) | 0.0375 (6) | |
C2 | 0.1398 (3) | 0.81375 (11) | 0.65504 (19) | 0.0367 (6) | |
C3 | 0.1871 (3) | 0.86150 (12) | 0.5923 (2) | 0.0432 (6) | |
C4 | 0.1608 (3) | 0.92174 (12) | 0.6162 (2) | 0.0517 (7) | |
H4 | 0.1951 | 0.9534 | 0.5733 | 0.062* | |
C5 | 0.0804 (3) | 0.93103 (12) | 0.7081 (3) | 0.0523 (7) | |
C6 | 0.0240 (3) | 0.88531 (12) | 0.7730 (2) | 0.0519 (7) | |
H6 | −0.0335 | 0.8948 | 0.8332 | 0.062* | |
C7 | 0.0542 (3) | 0.82570 (12) | 0.7472 (2) | 0.0464 (7) | |
H7 | 0.0187 | 0.7942 | 0.7898 | 0.056* | |
C8 | 0.2995 (4) | 0.61826 (11) | 0.76569 (19) | 0.0467 (7) | |
H8A | 0.3792 | 0.6116 | 0.8232 | 0.056* | |
H8B | 0.1951 | 0.6100 | 0.7937 | 0.056* | |
C9 | 0.3062 (3) | 0.68388 (11) | 0.72972 (19) | 0.0447 (6) | |
H9A | 0.4138 | 0.6933 | 0.7087 | 0.054* | |
H9B | 0.2813 | 0.7101 | 0.7894 | 0.054* | |
C10 | 0.1887 (3) | 0.69623 (11) | 0.63561 (19) | 0.0395 (6) | |
H10 | 0.0805 | 0.6884 | 0.6596 | 0.047* | |
C11 | 0.2218 (4) | 0.65205 (12) | 0.5461 (2) | 0.0507 (7) | |
H11A | 0.1436 | 0.6581 | 0.4874 | 0.061* | |
H11B | 0.3268 | 0.6604 | 0.5192 | 0.061* | |
C12 | 0.2153 (4) | 0.58721 (12) | 0.5825 (2) | 0.0523 (7) | |
H12A | 0.1074 | 0.5777 | 0.6028 | 0.063* | |
H12B | 0.2414 | 0.5608 | 0.5233 | 0.063* | |
C13 | 0.3179 (3) | 0.51047 (11) | 0.7099 (2) | 0.0441 (6) | |
H13A | 0.3105 | 0.4851 | 0.6461 | 0.053* | |
H13B | 0.2200 | 0.5051 | 0.7480 | 0.053* | |
C14 | 0.4572 (3) | 0.48869 (11) | 0.7812 (2) | 0.0474 (7) | |
H14A | 0.5519 | 0.4846 | 0.7393 | 0.057* | |
H14B | 0.4798 | 0.5179 | 0.8380 | 0.057* | |
C15 | 0.4152 (3) | 0.42850 (10) | 0.8288 (2) | 0.0382 (6) | |
C16 | 0.3326 (3) | 0.43048 (11) | 0.9267 (2) | 0.0446 (6) | |
C17 | 0.3373 (3) | 0.32160 (11) | 0.9231 (2) | 0.0402 (6) | |
C18 | 0.4442 (3) | 0.37363 (11) | 0.78350 (19) | 0.0392 (6) | |
C19 | 0.5206 (4) | 0.36680 (13) | 0.6777 (2) | 0.0557 (7) | |
H19A | 0.4397 | 0.3679 | 0.6208 | 0.084* | |
H19B | 0.5762 | 0.3287 | 0.6759 | 0.084* | |
H19C | 0.5951 | 0.3994 | 0.6684 | 0.084* | |
C20 | 0.3052 (4) | 0.26146 (13) | 0.9775 (3) | 0.0589 (8) | |
H20 | 0.4009 | 0.2362 | 0.9722 | 0.071* | 0.85 |
H20' | 0.1988 | 0.2505 | 0.9478 | 0.071* | 0.15 |
C21 | 0.2807 (5) | 0.2714 (2) | 1.0991 (4) | 0.0731 (14) | 0.823 (5) |
H21A | 0.2492 | 0.2335 | 1.1320 | 0.088* | 0.823 (5) |
H21B | 0.3801 | 0.2847 | 1.1343 | 0.088* | 0.823 (5) |
C21' | 0.194 (3) | 0.2599 (8) | 1.0543 (16) | 0.059 (5)* | 0.177 (5) |
H21C | 0.2285 | 0.2300 | 1.1075 | 0.071* | 0.177 (5) |
H21D | 0.0947 | 0.2451 | 1.0207 | 0.071* | 0.177 (5) |
C22 | 0.1568 (5) | 0.31708 (17) | 1.1125 (3) | 0.0850 (11) | |
H22A | 0.1315 | 0.3197 | 1.1877 | 0.102* | |
H22B | 0.0604 | 0.3053 | 1.0718 | 0.102* | |
C23 | 0.2119 (4) | 0.37704 (15) | 1.0748 (2) | 0.0643 (8) | |
H23A | 0.2838 | 0.3945 | 1.1295 | 0.077* | |
H23B | 0.1203 | 0.4038 | 1.0658 | 0.077* | |
O3 | 0.1799 (3) | 0.23263 (11) | 0.9224 (3) | 0.0890 (13) | 0.823 (5) |
H3 | 0.2103 | 0.1997 | 0.9003 | 0.133* | 0.823 (5) |
O3' | 0.391 (2) | 0.2197 (8) | 0.9559 (14) | 0.118 (7)* | 0.177 (5) |
H3' | 0.4856 | 0.2297 | 0.9625 | 0.177* | 0.177 (5) |
O4 | 0.8275 (16) | 0.5916 (7) | 0.5210 (7) | 0.086 (2) | 0.69 |
O5 | 0.6654 (13) | 0.6207 (5) | 0.6430 (12) | 0.120 (4) | 0.69 |
O6 | 0.6165 (11) | 0.5413 (5) | 0.5526 (7) | 0.089 (3) | 0.69 |
N5 | 0.7082 (3) | 0.58315 (14) | 0.5744 (2) | 0.0584 (7) | |
O4' | 0.640 (2) | 0.6163 (7) | 0.632 (2) | 0.069 (5) | 0.31 |
O5' | 0.670 (3) | 0.5314 (10) | 0.565 (2) | 0.127 (9) | 0.31 |
O6' | 0.837 (4) | 0.600 (2) | 0.552 (2) | 0.176 (14) | 0.31 |
U11 | U22 | U33 | U12 | U13 | U23 | |
F1 | 0.0704 (12) | 0.0454 (10) | 0.1252 (17) | 0.0094 (8) | 0.0184 (11) | −0.0060 (10) |
O1 | 0.0679 (13) | 0.0498 (12) | 0.0440 (11) | −0.0008 (9) | 0.0128 (10) | 0.0146 (9) |
O2 | 0.1027 (17) | 0.0433 (12) | 0.0812 (15) | 0.0030 (11) | 0.0313 (13) | −0.0196 (11) |
N1 | 0.0595 (15) | 0.0489 (14) | 0.0396 (12) | 0.0013 (11) | 0.0068 (11) | 0.0076 (10) |
N2 | 0.0362 (11) | 0.0363 (11) | 0.0364 (11) | −0.0011 (9) | 0.0041 (9) | 0.0015 (9) |
N3 | 0.0479 (13) | 0.0439 (13) | 0.0359 (11) | −0.0028 (10) | 0.0082 (9) | 0.0004 (10) |
N4 | 0.0565 (14) | 0.0301 (11) | 0.0508 (13) | 0.0033 (10) | 0.0063 (11) | −0.0068 (10) |
C1 | 0.0384 (13) | 0.0430 (14) | 0.0310 (13) | −0.0021 (11) | −0.0010 (11) | 0.0077 (11) |
C2 | 0.0359 (13) | 0.0370 (14) | 0.0370 (13) | −0.0007 (10) | 0.0003 (11) | 0.0062 (11) |
C3 | 0.0438 (15) | 0.0453 (15) | 0.0406 (14) | −0.0006 (12) | 0.0017 (12) | 0.0115 (12) |
C4 | 0.0480 (16) | 0.0374 (15) | 0.069 (2) | 0.0009 (12) | −0.0005 (15) | 0.0176 (14) |
C5 | 0.0422 (15) | 0.0370 (15) | 0.078 (2) | 0.0061 (12) | 0.0033 (15) | −0.0002 (14) |
C6 | 0.0444 (16) | 0.0525 (17) | 0.0595 (18) | 0.0051 (13) | 0.0114 (14) | −0.0003 (14) |
C7 | 0.0458 (15) | 0.0452 (15) | 0.0488 (16) | −0.0003 (12) | 0.0084 (13) | 0.0094 (13) |
C8 | 0.0687 (18) | 0.0389 (14) | 0.0328 (13) | 0.0043 (12) | 0.0054 (13) | 0.0001 (11) |
C9 | 0.0656 (18) | 0.0353 (14) | 0.0327 (13) | 0.0050 (12) | −0.0034 (12) | −0.0007 (11) |
C10 | 0.0403 (14) | 0.0387 (14) | 0.0399 (14) | 0.0021 (11) | 0.0064 (11) | 0.0054 (11) |
C11 | 0.0675 (19) | 0.0487 (16) | 0.0347 (14) | 0.0039 (13) | −0.0123 (13) | −0.0008 (12) |
C12 | 0.0672 (19) | 0.0433 (16) | 0.0447 (16) | 0.0039 (13) | −0.0181 (14) | −0.0020 (13) |
C13 | 0.0469 (15) | 0.0340 (14) | 0.0514 (15) | −0.0026 (11) | 0.0013 (13) | 0.0051 (12) |
C14 | 0.0425 (15) | 0.0415 (15) | 0.0582 (17) | −0.0025 (12) | 0.0026 (13) | 0.0104 (13) |
C15 | 0.0396 (14) | 0.0320 (13) | 0.0431 (14) | −0.0002 (10) | 0.0018 (11) | 0.0051 (11) |
C16 | 0.0500 (16) | 0.0350 (14) | 0.0496 (16) | 0.0017 (12) | 0.0095 (13) | −0.0043 (12) |
C17 | 0.0397 (14) | 0.0341 (14) | 0.0467 (15) | 0.0001 (11) | −0.0009 (12) | −0.0001 (12) |
C18 | 0.0371 (14) | 0.0431 (15) | 0.0371 (13) | 0.0006 (11) | −0.0014 (11) | 0.0027 (12) |
C19 | 0.0607 (18) | 0.0643 (19) | 0.0429 (15) | 0.0016 (14) | 0.0127 (14) | −0.0053 (14) |
C20 | 0.0535 (18) | 0.0423 (16) | 0.081 (2) | 0.0009 (14) | 0.0059 (17) | 0.0162 (15) |
C21 | 0.049 (2) | 0.099 (3) | 0.071 (3) | −0.004 (2) | −0.004 (2) | 0.054 (2) |
C22 | 0.093 (3) | 0.097 (3) | 0.067 (2) | −0.015 (2) | 0.025 (2) | 0.022 (2) |
C23 | 0.071 (2) | 0.081 (2) | 0.0419 (16) | −0.0121 (17) | 0.0167 (15) | −0.0057 (15) |
O3 | 0.0617 (19) | 0.0486 (16) | 0.154 (3) | −0.0114 (12) | −0.0312 (18) | 0.0149 (17) |
O4 | 0.048 (4) | 0.129 (5) | 0.083 (3) | −0.012 (3) | 0.028 (2) | 0.007 (3) |
O5 | 0.159 (9) | 0.103 (6) | 0.100 (5) | −0.019 (5) | 0.039 (6) | −0.024 (5) |
O6 | 0.070 (3) | 0.127 (7) | 0.071 (3) | −0.037 (4) | 0.016 (2) | −0.016 (3) |
N5 | 0.0556 (19) | 0.0624 (19) | 0.0579 (17) | 0.0019 (16) | 0.0097 (15) | 0.0076 (14) |
O4' | 0.042 (5) | 0.030 (5) | 0.138 (15) | 0.005 (4) | 0.036 (6) | −0.018 (7) |
O5' | 0.16 (2) | 0.054 (8) | 0.167 (17) | −0.032 (12) | 0.039 (14) | −0.035 (8) |
O6' | 0.065 (14) | 0.17 (2) | 0.30 (4) | 0.005 (12) | 0.09 (2) | 0.06 (3) |
F1—C5 | 1.350 (3) | C13—H13A | 0.9700 |
O1—C3 | 1.360 (3) | C13—H13B | 0.9700 |
O1—N1 | 1.431 (3) | C14—C15 | 1.500 (3) |
O2—C16 | 1.231 (3) | C14—H14A | 0.9700 |
N1—C1 | 1.301 (3) | C14—H14B | 0.9700 |
N2—C12 | 1.492 (3) | C15—C18 | 1.360 (3) |
N2—C8 | 1.493 (3) | C15—C16 | 1.426 (4) |
N2—C13 | 1.498 (3) | C17—C20 | 1.517 (4) |
N2—H2 | 0.9108 | C18—C19 | 1.495 (3) |
N3—C17 | 1.359 (3) | C19—H19A | 0.9600 |
N3—C16 | 1.405 (3) | C19—H19B | 0.9600 |
N3—C23 | 1.483 (3) | C19—H19C | 0.9600 |
N4—C17 | 1.291 (3) | C20—O3' | 1.204 (17) |
N4—C18 | 1.360 (3) | C20—C21' | 1.362 (18) |
N4—H4A | 0.8594 | C20—O3 | 1.383 (4) |
C1—C2 | 1.433 (3) | C20—C21 | 1.552 (5) |
C1—C10 | 1.492 (3) | C20—H20 | 0.9798 |
C2—C3 | 1.378 (3) | C20—H20' | 0.9803 |
C2—C7 | 1.401 (3) | C21—C22 | 1.459 (5) |
C3—C4 | 1.380 (4) | C21—H21A | 0.9700 |
C4—C5 | 1.365 (4) | C21—H21B | 0.9700 |
C4—H4 | 0.9300 | C21'—C22 | 1.492 (18) |
C5—C6 | 1.386 (4) | C21'—H21C | 0.9700 |
C6—C7 | 1.378 (4) | C21'—H21D | 0.9700 |
C6—H6 | 0.9300 | C22—C23 | 1.482 (4) |
C7—H7 | 0.9300 | C22—H22A | 0.9700 |
C8—C9 | 1.515 (3) | C22—H22B | 0.9700 |
C8—H8A | 0.9700 | C23—H23A | 0.9700 |
C8—H8B | 0.9700 | C23—H23B | 0.9700 |
C9—C10 | 1.523 (3) | O3—H20' | 0.5247 |
C9—H9A | 0.9700 | O3—H3 | 0.8192 |
C9—H9B | 0.9700 | O3'—H20 | 0.4223 |
C10—C11 | 1.514 (3) | O3'—H3' | 0.8231 |
C10—H10 | 0.9800 | O4—N5 | 1.235 (13) |
C11—C12 | 1.500 (3) | O5—N5 | 1.252 (11) |
C11—H11A | 0.9700 | O6—N5 | 1.223 (10) |
C11—H11B | 0.9700 | N5—O5' | 1.19 (2) |
C12—H12A | 0.9700 | N5—O4' | 1.187 (18) |
C12—H12B | 0.9700 | N5—O6' | 1.19 (3) |
C13—C14 | 1.513 (3) | ||
C3—O1—N1 | 107.05 (18) | O2—C16—N3 | 119.3 (2) |
C1—N1—O1 | 107.3 (2) | O2—C16—C15 | 124.6 (2) |
C12—N2—C8 | 110.77 (19) | N3—C16—C15 | 116.0 (2) |
C12—N2—C13 | 110.04 (18) | N4—C17—N3 | 122.7 (2) |
C8—N2—C13 | 112.10 (18) | N4—C17—C20 | 118.0 (2) |
C12—N2—H2 | 107.9 | N3—C17—C20 | 119.3 (2) |
C8—N2—H2 | 107.9 | C15—C18—N4 | 122.0 (2) |
C13—N2—H2 | 108.0 | C15—C18—C19 | 123.0 (2) |
C17—N3—C16 | 120.4 (2) | N4—C18—C19 | 115.0 (2) |
C17—N3—C23 | 124.3 (2) | C18—C19—H19A | 109.5 |
C16—N3—C23 | 115.3 (2) | C18—C19—H19B | 109.5 |
C17—N4—C18 | 119.8 (2) | H19A—C19—H19B | 109.5 |
C17—N4—H4A | 120.0 | C18—C19—H19C | 109.5 |
C18—N4—H4A | 120.2 | H19A—C19—H19C | 109.5 |
N1—C1—C2 | 111.2 (2) | H19B—C19—H19C | 109.5 |
N1—C1—C10 | 120.3 (2) | O3'—C20—C21' | 124.6 (12) |
C2—C1—C10 | 128.5 (2) | O3'—C20—O3 | 89.1 (9) |
C3—C2—C7 | 119.3 (2) | C21'—C20—O3 | 79.1 (9) |
C3—C2—C1 | 104.2 (2) | O3'—C20—C17 | 116.7 (9) |
C7—C2—C1 | 136.5 (2) | C21'—C20—C17 | 118.3 (8) |
O1—C3—C2 | 110.2 (2) | O3—C20—C17 | 108.9 (3) |
O1—C3—C4 | 125.8 (2) | O3'—C20—C21 | 115.4 (9) |
C2—C3—C4 | 124.1 (3) | O3—C20—C21 | 114.9 (3) |
C5—C4—C3 | 114.4 (2) | C17—C20—C21 | 110.2 (3) |
C5—C4—H4 | 122.8 | C21'—C20—H20 | 128.1 |
C3—C4—H4 | 122.8 | O3—C20—H20 | 108.0 |
F1—C5—C4 | 117.6 (2) | C17—C20—H20 | 107.9 |
F1—C5—C6 | 117.6 (3) | C21—C20—H20 | 106.6 |
C4—C5—C6 | 124.8 (3) | O3'—C20—H20' | 105.5 |
C7—C6—C5 | 119.1 (3) | C21'—C20—H20' | 67.8 |
C7—C6—H6 | 120.4 | C17—C20—H20' | 102.8 |
C5—C6—H6 | 120.4 | C21—C20—H20' | 104.4 |
C6—C7—C2 | 118.3 (2) | H20—C20—H20' | 124.4 |
C6—C7—H7 | 120.8 | C22—C21—C20 | 109.3 (3) |
C2—C7—H7 | 120.8 | C22—C21—H21A | 109.8 |
N2—C8—C9 | 111.82 (19) | C20—C21—H21A | 109.8 |
N2—C8—H8A | 109.3 | C22—C21—H21B | 109.8 |
C9—C8—H8A | 109.3 | C20—C21—H21B | 109.8 |
N2—C8—H8B | 109.3 | H21A—C21—H21B | 108.3 |
C9—C8—H8B | 109.3 | C20—C21'—C22 | 118.7 (13) |
H8A—C8—H8B | 107.9 | C22—C21'—H20' | 128.7 |
C8—C9—C10 | 111.6 (2) | C20—C21'—H21C | 107.6 |
C8—C9—H9A | 109.3 | C22—C21'—H21C | 107.6 |
C10—C9—H9A | 109.3 | H20'—C21'—H21C | 123.3 |
C8—C9—H9B | 109.3 | C20—C21'—H21D | 107.6 |
C10—C9—H9B | 109.3 | C22—C21'—H21D | 107.6 |
H9A—C9—H9B | 108.0 | H20'—C21'—H21D | 65.3 |
C1—C10—C11 | 113.1 (2) | H21C—C21'—H21D | 107.1 |
C1—C10—C9 | 110.9 (2) | C21—C22—C23 | 110.3 (3) |
C11—C10—C9 | 108.7 (2) | C21'—C22—C23 | 121.7 (7) |
C1—C10—H10 | 108.0 | C21—C22—H22A | 109.6 |
C11—C10—H10 | 108.0 | C21'—C22—H22A | 125.3 |
C9—C10—H10 | 108.0 | C23—C22—H22A | 109.6 |
C12—C11—C10 | 112.3 (2) | C21—C22—H22B | 109.6 |
C12—C11—H11A | 109.1 | C21'—C22—H22B | 72.8 |
C10—C11—H11A | 109.1 | C23—C22—H22B | 109.6 |
C12—C11—H11B | 109.1 | H22A—C22—H22B | 108.1 |
C10—C11—H11B | 109.1 | C22—C23—N3 | 113.4 (3) |
H11A—C11—H11B | 107.9 | C22—C23—H23A | 108.9 |
N2—C12—C11 | 111.7 (2) | N3—C23—H23A | 108.9 |
N2—C12—H12A | 109.3 | C22—C23—H23B | 108.9 |
C11—C12—H12A | 109.3 | N3—C23—H23B | 108.9 |
N2—C12—H12B | 109.3 | H23A—C23—H23B | 107.7 |
C11—C12—H12B | 109.3 | C20—O3—H3 | 109.5 |
H12A—C12—H12B | 107.9 | H20'—O3—H3 | 140.8 |
N2—C13—C14 | 114.5 (2) | C20—O3'—H20 | 49.0 |
N2—C13—H13A | 108.6 | C20—O3'—H3' | 110.7 |
C14—C13—H13A | 108.6 | H20—O3'—H3' | 63.4 |
N2—C13—H13B | 108.6 | O5'—N5—O4' | 120.8 (15) |
C14—C13—H13B | 108.6 | O5'—N5—O4 | 108.4 (14) |
H13A—C13—H13B | 107.6 | O4'—N5—O4 | 130.7 (12) |
C15—C14—C13 | 109.0 (2) | O4'—N5—O6 | 106.5 (11) |
C15—C14—H14A | 109.9 | O4—N5—O6 | 120.5 (8) |
C13—C14—H14A | 109.9 | O5'—N5—O5 | 127.9 (14) |
C15—C14—H14B | 109.9 | O4—N5—O5 | 121.8 (9) |
C13—C14—H14B | 109.9 | O6—N5—O5 | 117.1 (7) |
H14A—C14—H14B | 108.3 | O5'—N5—O6' | 122 (2) |
C18—C15—C16 | 118.8 (2) | O4'—N5—O6' | 114 (2) |
C18—C15—C14 | 125.0 (2) | O6—N5—O6' | 139.3 (18) |
C16—C15—C14 | 116.1 (2) | O5—N5—O6' | 103.5 (19) |
C3—O1—N1—C1 | 0.0 (3) | C17—N3—C16—C15 | 0.0 (3) |
O1—N1—C1—C2 | 0.7 (3) | C23—N3—C16—C15 | 179.0 (2) |
O1—N1—C1—C10 | −176.8 (2) | C18—C15—C16—O2 | −176.2 (3) |
N1—C1—C2—C3 | −1.2 (3) | C14—C15—C16—O2 | 1.2 (4) |
C10—C1—C2—C3 | 176.1 (2) | C18—C15—C16—N3 | 3.4 (4) |
N1—C1—C2—C7 | 178.0 (3) | C14—C15—C16—N3 | −179.2 (2) |
C10—C1—C2—C7 | −4.7 (5) | C18—N4—C17—N3 | 2.0 (4) |
N1—O1—C3—C2 | −0.8 (3) | C18—N4—C17—C20 | −176.8 (2) |
N1—O1—C3—C4 | 178.5 (2) | C16—N3—C17—N4 | −2.8 (4) |
C7—C2—C3—O1 | −178.2 (2) | C23—N3—C17—N4 | 178.3 (2) |
C1—C2—C3—O1 | 1.2 (3) | C16—N3—C17—C20 | 176.0 (2) |
C7—C2—C3—C4 | 2.5 (4) | C23—N3—C17—C20 | −2.8 (4) |
C1—C2—C3—C4 | −178.1 (2) | C16—C15—C18—N4 | −4.4 (4) |
O1—C3—C4—C5 | 179.9 (2) | C14—C15—C18—N4 | 178.4 (2) |
C2—C3—C4—C5 | −0.9 (4) | C16—C15—C18—C19 | 176.1 (2) |
C3—C4—C5—F1 | 177.3 (2) | C14—C15—C18—C19 | −1.1 (4) |
C3—C4—C5—C6 | −1.6 (4) | C17—N4—C18—C15 | 1.7 (4) |
F1—C5—C6—C7 | −176.4 (2) | C17—N4—C18—C19 | −178.7 (2) |
C4—C5—C6—C7 | 2.4 (4) | N4—C17—C20—O3' | 25.3 (10) |
C5—C6—C7—C2 | −0.7 (4) | N3—C17—C20—O3' | −153.5 (10) |
C3—C2—C7—C6 | −1.6 (4) | N4—C17—C20—C21' | −161.0 (11) |
C1—C2—C7—C6 | 179.3 (3) | N3—C17—C20—C21' | 20.1 (12) |
C12—N2—C8—C9 | −55.1 (3) | N4—C17—C20—O3 | −73.5 (3) |
C13—N2—C8—C9 | −178.4 (2) | N3—C17—C20—O3 | 107.6 (3) |
N2—C8—C9—C10 | 56.2 (3) | N4—C17—C20—C21 | 159.6 (3) |
N1—C1—C10—C11 | −17.7 (3) | N3—C17—C20—C21 | −19.3 (4) |
C2—C1—C10—C11 | 165.2 (2) | O3'—C20—C21—C22 | −171.6 (10) |
N1—C1—C10—C9 | 104.7 (3) | C21'—C20—C21—C22 | −57.1 (13) |
C2—C1—C10—C9 | −72.4 (3) | O3—C20—C21—C22 | −70.0 (4) |
C8—C9—C10—C1 | 180.0 (2) | C17—C20—C21—C22 | 53.5 (4) |
C8—C9—C10—C11 | −55.1 (3) | O3'—C20—C21'—C22 | 148.9 (15) |
C1—C10—C11—C12 | 179.3 (2) | O3—C20—C21'—C22 | −129.9 (17) |
C9—C10—C11—C12 | 55.7 (3) | C17—C20—C21'—C22 | −24 (2) |
C8—N2—C12—C11 | 55.1 (3) | C21—C20—C21'—C22 | 62.1 (14) |
C13—N2—C12—C11 | 179.6 (2) | C20—C21—C22—C21' | 49.6 (12) |
C10—C11—C12—N2 | −56.7 (3) | C20—C21—C22—C23 | −66.4 (4) |
C12—N2—C13—C14 | 163.5 (2) | C20—C21'—C22—C21 | −69.2 (16) |
C8—N2—C13—C14 | −72.8 (3) | C20—C21'—C22—C23 | 13 (2) |
N2—C13—C14—C15 | 167.7 (2) | C21—C22—C23—N3 | 43.2 (4) |
C13—C14—C15—C18 | 89.9 (3) | C21'—C22—C23—N3 | 3.9 (12) |
C13—C14—C15—C16 | −87.4 (3) | C17—N3—C23—C22 | −8.4 (4) |
C17—N3—C16—O2 | 179.7 (2) | C16—N3—C23—C22 | 172.7 (3) |
C23—N3—C16—O2 | −1.4 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2···O4′ | 0.91 | 1.94 | 2.823 (18) | 164 |
N2—H2···O5 | 0.91 | 2.15 | 3.028 (12) | 161 |
N2—H2···O6 | 0.91 | 2.23 | 2.999 (9) | 142 |
N2—H2···N5 | 0.91 | 2.56 | 3.465 (3) | 170 |
N2—H2···O5′ | 0.91 | 2.58 | 3.36 (3) | 144 |
O3′—H3′···N1i | 0.82 | 2.30 | 3.117 (18) | 169 |
O3—H3···O5i | 0.82 | 2.11 | 2.915 (12) | 168 |
O3—H3···O4′i | 0.82 | 2.27 | 3.064 (19) | 163 |
O3—H3···O6′i | 0.82 | 2.30 | 2.93 (4) | 134 |
O3—H3···O4i | 0.82 | 2.60 | 3.187 (16) | 130 |
O3—H3···N5i | 0.82 | 2.67 | 3.423 (4) | 153 |
Symmetry code: (i) −x+1, y−1/2, −z+3/2. |
Experimental details
Crystal data | |
Chemical formula | C23H29FN4O3+·NO3− |
Mr | 490.51 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 293 |
a, b, c (Å) | 8.3642 (8), 22.032 (2), 12.4485 (13) |
β (°) | 92.311 (3) |
V (Å3) | 2292.1 (4) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.11 |
Crystal size (mm) | 0.30 × 0.25 × 0.24 |
Data collection | |
Diffractometer | Rigaku SCXmini diffractometer |
Absorption correction | Multi-scan (CrystalClear; Rigaku, 2005) |
Tmin, Tmax | 0.968, 0.974 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 23571, 5234, 2824 |
Rint | 0.063 |
(sin θ/λ)max (Å−1) | 0.649 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.063, 0.178, 1.06 |
No. of reflections | 5234 |
No. of parameters | 353 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.42, −0.45 |
Computer programs: CrystalClear (Rigaku, 2005), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), DIAMOND (Brandenburg & Putz, 2005).
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2···O4' | 0.91 | 1.94 | 2.823 (18) | 164 |
N2—H2···O5 | 0.91 | 2.15 | 3.028 (12) | 161 |
N2—H2···O6 | 0.91 | 2.23 | 2.999 (9) | 142 |
N2—H2···N5 | 0.91 | 2.56 | 3.465 (3) | 170 |
N2—H2···O5' | 0.91 | 2.58 | 3.36 (3) | 144 |
O3'—H3'···N1i | 0.82 | 2.30 | 3.117 (18) | 169 |
O3—H3···O5i | 0.82 | 2.11 | 2.915 (12) | 168 |
O3—H3···O4'i | 0.82 | 2.27 | 3.064 (19) | 163 |
O3—H3···O6'i | 0.82 | 2.30 | 2.93 (4) | 134 |
O3—H3···O4i | 0.82 | 2.60 | 3.187 (16) | 130 |
O3—H3···N5i | 0.82 | 2.67 | 3.423 (4) | 153 |
Symmetry code: (i) −x+1, y−1/2, −z+3/2. |
Acknowledgements
This work was supported by the Jiangsu Innovation Fund (SBY201220255).
References
Brandenburg, K. & Putz, H. (2005). DIAMOND. Crystal Impact GbR, Bonn, Germany. Google Scholar
Luo, Y. H., Ma, Y. T., Bao, Q. Q. & Sun, B. W. (2012). J. Chem. Crystallogr. 42, 628–632. Web of Science CSD CrossRef CAS Google Scholar
Rigaku. (2005). CrystalClear. Rigaku Corporation, Tokyo, Japan. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Spina, E. & Crupi, R. (2011). J. Cent. Nerv. Syst. Dis. 3, 27–41. CrossRef CAS PubMed Google Scholar
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In recent years, the studies of polymorphism for pharmaceutical ingredients have received much attention, different polymorphs can affect shelf life,durability, solubility, as well as bioavailability and manufacturing of a drug (Luo et al.,2012). Paliperidone or 9-hydroxyrisperidone, is one of the most recently available atypical antipsychotics (Spina & Crupi, 2011). It is a benzisoxazole derivative and the major active metabolite of risperidone, a widely used atypical antipsychotic approved for the treatment of schizophrenia and other psychiatric disorders. In view of the importance of the polymorphs of paliperidone, we reported here a pesudo-polymorphism of paliperidone: paliperidonium nitrate.
The asymmetric unit of the title compound consisting of a paliperidone cation and a nitrate ion (Fig. 1) The piperidine ring of the paliperidone cation displays a chair conformation with the nitrogen atoms charged with a hydrion, while the ring which bears the hydroxy group exhibits a half-chair conformation. The hydroxy group as well as the neighbour carbon atom (C21), are disordered over two positions, both with site occupancy factors of 0.82263 and 0.17737.
In the crystal, inteicate classical O—H···N, O—H···O, N—H···O and N—H···N hydrogen bonds between the paliperidone cation and the nitrate ion are observed, which connect the molecules into complex structure.(Fig. 2).