4-[4-(4-Fluoro­phen­yl)-2-methyl-5-oxo-2,5-dihydro­isoxazol-3-yl]-1-methyl­pyridinium iodide–4-[3-(4-fluoro­phen­yl)-2-methyl-5-oxo-2,5-dihydro­isoxazol-4-yl]-1-methyl­pyridinium iodide (0.6/0.4)

Margutti, S.; Schollmeyer, D.; Laufer, S.

doi:10.1107/S1600536807055985

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 64| Part 1| January 2008| Pages o298-o299

https://doi.org/10.1107/S1600536807055985

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4-[4-(4-Fluorophenyl)-2-methyl-5-oxo-2,5-dihydroisoxazol-3-yl]-1-methylpyridinium iodide–4-[3-(4-fluorophenyl)-2-methyl-5-oxo-2,5-dihydroisoxazol-4-yl]-1-methylpyridinium iodide (0.6/0.4)

Simona Margutti,^a Dieter Schollmeyer ^b and Stefan Laufer ^a ^*

^aInstitute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry, Eberhard-Karls-University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany, and ^bDepartment of Organic Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, D-55099 Mainz, Germany
^*Correspondence e-mail: stefan.laufer@uni-tuebingen.de

(Received 30 October 2007; accepted 5 November 2007; online 18 December 2007)

The crystal structure of the title compound, C₁₆H₁₆FN₂O₂⁺·I⁻, was determined as part of a study of the biological activity of isoxazolone derivatives as p38 mitogen-activated protein kinase (MAPK) inhibitors. The X-ray crystal structure of 4-[4-(4-fluorophenyl)-2-methyl-5-oxo-2,5-dihydroisoxazol-3-yl]-1-methylpyridinium iodide showed the presence of the regioisomer 4-[3-(4-fluorophenyl)-2-methyl-5-oxo-2,5-dihydroisoxazol-4-yl]-1-methylpyridinium iodide. The synthesis of the former compound was achieved by reacting 4-(4-fluorophenyl)-3-(4-pyridyl)isoxazol-5(2H)-one after treatment with Et₃N in dimethylformamide, with iodomethane. The unexpected formation of the regioisomer could be explained by a rearrangement occurring via aziridine of the isoxazolone compound. The regioisomers have site occupancies of 0.632 (4)/0.368 (4). The two six members rings make a dihedral angle of 66.8 (2)°.

Related literature

For general background on the pharmaceutical applications of isoxazolones, see: Laughlin et al. (2005 ); Clark et al. (2002 ); Wang et al. (1998 ); Foster et al. (2000 ); Adams et al. (1998 ); Laufer & Wagner (2002 ); de Laszlo et al. (1998 ); Laufer et al. (2005 , 2006 ); Revesz et al. (2000 ); Ohkawa et al. (2001 ). The aziridine rearrangement of isoxazolones was described by Nishiwaki & Saito (1971 ) and Sauers (1990 ).

Experimental

Crystal data

C₁₅H₁₂FN₂O₂⁺·I⁻
M_r = 398.17
Monoclinic, P 2₁ /c
a = 10.2804 (4) Å
b = 20.5895 (9) Å
c = 7.4907 (3) Å
β = 96.8828 (14)°
V = 1574.12 (11) Å³
Z = 4
Mo Kα radiation
μ = 2.05 mm⁻¹
T = 193 (2) K
0.52 × 0.20 × 0.08 mm

Data collection

Bruker SMART APEXII CCD diffractometer
Absorption correction: multi-scan (APEX2; Bruker, 2006 ) T_min = 0.415, T_max = 0.853
27681 measured reflections
3897 independent reflections
3369 reflections with I > 2σ(I)
R_int = 0.126

Refinement

R[F² > 2σ(F²)] = 0.040
wR(F²) = 0.115
S = 1.07
3897 reflections
188 parameters
H-atom parameters constrained
Δρ_max = 1.60 e Å⁻³
Δρ_min = −0.51 e Å⁻³

Data collection: APEX2 (Bruker, 2006); cell refinement: APEX2; data reduction: APEX2; program(s) used to solve structure: SIR92 (Altomare et al., 1994 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997 ); molecular graphics: ORTEP (Johnson, 1968 ) and PLATON (Spek, 2003 ); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S1600536807055985/bt2577sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536807055985/bt2577Isup2.hkl

checkCIF report

Comment top

Compound (II) (Scheme 1) was prepared in the course of our study on isoxazolones derivatives bearing the typical vicinal 4-pyridyl and 4-fluorophenyl pharmacophores of MAP Kinase inhibitors. Isoxazolones are described in the literature as inhibitors for p38 MAP Kinase (Laughlin et al., 2005; Clark et al., 2002).

The prototypical pyridinylimidazole SB 203580 is one of the best studied p38 inhibitors reported until now. Fig. 1 shows the most important interactions between the ATP binding sites of p38 kinase and the imidazole inhibitor SB203580 (Wang et al., 1998). The 4-fluorophenyl ring of SB203580 occupies a hydrophobic back pocket gaining selectivity. Vicinal to this interaction site, 4-pyridinyl moiety forms a hydrogen bond from the backbone NH group of Met 109 of p38 MAP Kinase (Fig. 1).

However, certain liver toxicities, such as increased liver size and increased cytochrome P450 induction, have been reported (Foster et al., 2000; Adams et al., 1998). In light of this potential toxicity and the risks associated with developing human drugs, a continuing need exist for potent new small molecules inhibitors of cytokine production with improved pharmacokinetic and safety profiles.

Several research groups have undertaken studies in which the imidazole ring was replaced by other 5- or 6- membered heterocycles (Laufer & Wagner, 2002; de Laszlo et al., 1998; Laufer et al., 2006; Revesz et al., 2000; Ohkawa et al., 2001). Replacement of the core heterocycle representing a strategy to dissect inhibition of p38 from interferences with cytochrome P450 (CYP450).

Accordingly, and based on the research published by Laughlin and co-authors (Laughlin et al., 2005), we plane to prepare N-alkylated derivatives of compound (I) in order to get more accurate and comparable information about isoxazolones as p38 MAP Kinase inhibitors in terms of biological activity.

By testing compounds (I) and (II) in the in vitro p38-alpha MAPK assay (Laufer et al., 2005), only compound (I) was found to posses biological activity.

The loss of the biological activity of compound (II) can be attributed to the absence of hydrogen bond donor on the pyridine ring and, consequentely, impossibility of interaction with Met109.

Related literature top

For general background on the pharmaceutical applications of isoxazolones, see: Laughlin et al. (2005); Clark et al. (2002); Wang et al. (1998); Foster et al. (2000); Adams et al. (1998); Laufer & Wagner (2002); de Laszlo et al. (1998); Laufer et al. (2005, 2006); Revesz et al. (2000); Ohkawa et al. (2001). The aziridine rearrangement of isoxazolones was described by Nishiwaki & Saito (1971) and Sauers (1990). [These last two references are not cited anywhere but here. Please provide revised text to be added to the appropriate section of the CIF, or they will be removed]

Experimental top

For the synthesis of 2-(4-Fluoro-phenyl)-3-oxo-3-pyridin-4-yl-propionic acid ethyl ester (see scheme 1), to a suspension of 3.3 g (26.8 mmol) of isonicotinic acid in 15 ml of DMF, 7.3 g (45 mmol) of CDI were added. The reaction mixture was stirred at 298 K for 1 h. The limpid solution was then cooled at 273 K and 5 g (27.4 mmol) of (4-Fluoro-phenyl)-acetic acid ethyl and 1.7 g (70.8 mmol) of NaH were added. The reaction mixture was stirred at 273 K for 15 min, then the temperature was raised to 298 K and kept under vigorous stirring for 4 h. The reaction was then poured into water/ice, the pH adjusted to value 6 and extracted with ethylacetate. The combined organic layers were then collected, dried over Na₂SO₄ and concentrated under vacuum affording an oil that was chromatographed over SiO₂ using acetone as eluent y ielding 75% of 2-(4-Fluoro-phenyl)-3-oxo-3-pyridin-4-yl-propionic acid ethyl ester. For the synthesis of (I), a suspension of 5.2 g (18.1 mmol) of 2-(4-Fluoro-phenyl)-3-oxo-3-pyridin -4-yl-propionic acid ethyl ester and 1.41 g (20.27 mmol) of hydroxylamine hydrochloride in 1.5 ml of H₂O was warmed to 353 K. 8 ml of MeOH were added and the resulting solution allowed to reflux 4 h. The reaction mixture was then cooled to 298 K and stored at 277 K overnight whereupon a yellow solide precipitated, yielding 75% of (I). For the synthesis of (II) and (III), a suspension of 620 mg (2.5 mmol) of (I) in 1 ml of DMF was added of 0.620 ml (4.5 mmol) of Et3N and refluxed for 2 h. The reaction mixture was then cooled at 298 K, added of 0.231 ml (3.75 mmol) of iodomethane and stirred at 298 K for 2 h. The reaction mixture was then added of ethylacetate and the resulting precipitate separated by filtration and then crystalized from MeOH yielding 54% of (II) and (III).

Structure description top

By testing compounds (I) and (II) in the in vitro p38-alpha MAPK assay (Laufer et al., 2005), only compound (I) was found to posses biological activity.

The loss of the biological activity of compound (II) can be attributed to the absence of hydrogen bond donor on the pyridine ring and, consequentely, impossibility of interaction with Met109.

For general background on the pharmaceutical applications of isoxazolones, see: Laughlin et al. (2005); Clark et al. (2002); Wang et al. (1998); Foster et al. (2000); Adams et al. (1998); Laufer & Wagner (2002); de Laszlo et al. (1998); Laufer et al. (2005, 2006); Revesz et al. (2000); Ohkawa et al. (2001). The aziridine rearrangement of isoxazolones was described by Nishiwaki & Saito (1971) and Sauers (1990). [These last two references are not cited anywhere but here. Please provide revised text to be added to the appropriate section of the CIF, or they will be removed]

Computing details top

Data collection: APEX2 (Bruker, 2006); cell refinement: APEX2 (Bruker, 2006); data reduction: APEX2 (Bruker, 2006); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP (Johnson, 1968) and PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997).

Figures top

	Fig. 1. Schematic drawing of important interactions between the prototypical pyridin-4-yl imidazole inhibitor SB 203580 and the ATP binding site of p38.
	Fig. 2. Schematic drawings of 4-[4-(4-Fluoro-phenyl)-2-methyl-5-oxo-2,5-dihydro-isoxazol-3-yl]-1-methyl- pyridinium iodide, (II), and 4-[3-(4-Fluoro-phenyl)-2-methyl-5-oxo-2,5-dihydro-isoxazol-3-yl]-1-methyl- pyridinium iodide, (III).
	Fig. 3. ORTEP (Johnson, 1968) view of (II) and (III). Displacement ellipsoids are drawn at the 50% probability level. H atoms are depicted as circles of arbitrary size.
	Fig. 4. The formation of the title compound.

4-[4-(4-Fluorophenyl)-2-methyl-5-oxo-2,5-dihydroisoxazol-3-yl]-1- methylpyridinium iodide– 4-[3-(4-fluorophenyl)-2-methyl-5-oxo-2,5-dihydroisoxazol-4-yl]-1-methyl- pyridinium iodide (0.6/0.4) top

Crystal data top

C₁₅H₁₂FN₂O₂⁺·I⁻	F(000) = 776
M_r = 398.17	D_x = 1.680 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71069 Å
Hall symbol: -P 2ybc	Cell parameters from 6868 reflections
a = 10.2804 (4) Å	θ = 2.7–28.3°
b = 20.5895 (9) Å	µ = 2.05 mm⁻¹
c = 7.4907 (3) Å	T = 193 K
β = 96.8828 (14)°	Block, brown
V = 1574.12 (11) Å³	0.52 × 0.20 × 0.08 mm
Z = 4

Data collection top

Bruker APEXII CCD diffractometer	3897 independent reflections
Radiation source: sealed Tube	3369 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.126
CCD scan	θ_max = 28.4°, θ_min = 2.0°
Absorption correction: multi-scan (APEX2; Bruker, 2006)	h = −13→13
T_min = 0.415, T_max = 0.853	k = −27→27
27681 measured reflections	l = −9→9

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)] = 0.040	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.115	H-atom parameters constrained
S = 1.07	w = 1/[σ²(F_o²) + (0.0617P)² + 2.8681P] where P = (F_o² + 2F_c²)/3
3897 reflections	(Δ/σ)_max = 0.001
188 parameters	Δρ_max = 1.60 e Å⁻³
0 restraints	Δρ_min = −0.51 e Å⁻³

Crystal data top

C₁₅H₁₂FN₂O₂⁺·I⁻	V = 1574.12 (11) Å³
M_r = 398.17	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 10.2804 (4) Å	µ = 2.05 mm⁻¹
b = 20.5895 (9) Å	T = 193 K
c = 7.4907 (3) Å	0.52 × 0.20 × 0.08 mm
β = 96.8828 (14)°

Data collection top

Bruker APEXII CCD diffractometer	3897 independent reflections
Absorption correction: multi-scan (APEX2; Bruker, 2006)	3369 reflections with I > 2σ(I)
T_min = 0.415, T_max = 0.853	R_int = 0.126
27681 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.040	0 restraints
wR(F²) = 0.115	H-atom parameters constrained
S = 1.07	Δρ_max = 1.60 e Å⁻³
3897 reflections	Δρ_min = −0.51 e Å⁻³
188 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	Occ. (<1)
F1A	1.0107 (3)	0.20467 (16)	1.6192 (4)	0.0292 (4)	0.632 (4)
F1B	0.3217 (5)	0.1835 (3)	0.8219 (7)	0.0292 (4)	0.368 (4)
C1	0.9450 (4)	0.08719 (19)	0.9398 (5)	0.0327 (7)
C2	0.8322 (4)	0.07466 (19)	0.8261 (5)	0.0333 (7)
N3	0.8565 (3)	0.0373 (2)	0.6894 (5)	0.0458 (9)
O4	0.9887 (3)	0.02271 (16)	0.7079 (4)	0.0439 (7)
C5	1.0475 (4)	0.0546 (2)	0.8619 (6)	0.0384 (8)
C6	0.7766 (4)	0.0089 (2)	0.5375 (6)	0.0408 (9)
H6A	0.8320	−0.0168	0.4667	0.061*
H6B	0.7337	0.0435	0.4623	0.061*
H6C	0.7100	−0.0191	0.5806	0.061*
O7	1.1646 (3)	0.04901 (16)	0.8994 (5)	0.0489 (8)
C8	0.9607 (4)	0.12052 (18)	1.1149 (5)	0.0332 (8)
C9	0.8538 (4)	0.1315 (2)	1.2097 (6)	0.0359 (8)
H9	0.7687	0.1187	1.1584	0.043*
C10	0.8700 (4)	0.1609 (2)	1.3781 (6)	0.0399 (9)
H10	0.7969	0.1691	1.4412	0.048*
C11A	0.9937 (5)	0.1776 (2)	1.4501 (6)	0.0462 (9)	0.632 (4)
N11B	0.9937 (5)	0.1776 (2)	1.4501 (6)	0.0462 (9)	0.368 (4)
H11B	1.0046	0.1958	1.5571	0.055*	0.368 (4)
C12	1.1020 (4)	0.1672 (2)	1.3625 (6)	0.0458 (10)
H12	1.1868	0.1795	1.4162	0.055*
C13	1.0846 (4)	0.1386 (2)	1.1952 (6)	0.0413 (9)
H13	1.1586	0.1310	1.1333	0.050*
C15	0.6988 (4)	0.10094 (19)	0.8287 (5)	0.0312 (7)
C16	0.5906 (4)	0.06123 (19)	0.8311 (5)	0.0336 (7)
H16	0.6003	0.0153	0.8348	0.040*
C17	0.4681 (4)	0.0892 (2)	0.8282 (5)	0.0352 (8)
H17	0.3932	0.0623	0.8308	0.042*
N18A	0.4542 (3)	0.15364 (17)	0.8217 (4)	0.0292 (4)	0.632 (4)
H18A	0.3753	0.1705	0.8193	0.035*	0.632 (4)
C18B	0.4542 (3)	0.15364 (17)	0.8217 (4)	0.0292 (4)	0.368 (4)
C19	0.5569 (4)	0.1931 (2)	0.8188 (6)	0.0364 (8)
H19	0.5441	0.2388	0.8156	0.044*
C20	0.6822 (4)	0.16808 (19)	0.8204 (5)	0.0354 (8)
H20	0.7552	0.1961	0.8160	0.042*
I1	0.47781 (2)	0.126317 (12)	0.31747 (3)	0.03385 (11)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1A	0.0284 (10)	0.0371 (11)	0.0211 (9)	0.0016 (8)	−0.0013 (7)	−0.0038 (8)
F1B	0.0284 (10)	0.0371 (11)	0.0211 (9)	0.0016 (8)	−0.0013 (7)	−0.0038 (8)
C1	0.0289 (17)	0.0352 (19)	0.0353 (18)	0.0032 (14)	0.0087 (14)	0.0040 (14)
C2	0.0329 (18)	0.0339 (19)	0.0339 (18)	0.0020 (14)	0.0065 (14)	0.0026 (14)
N3	0.0312 (17)	0.061 (2)	0.045 (2)	0.0125 (16)	0.0037 (15)	−0.0117 (17)
O4	0.0336 (14)	0.0525 (18)	0.0474 (17)	0.0086 (13)	0.0122 (12)	−0.0064 (14)
C5	0.0325 (19)	0.038 (2)	0.045 (2)	0.0013 (16)	0.0092 (16)	0.0042 (16)
C6	0.040 (2)	0.042 (2)	0.042 (2)	0.0019 (17)	0.0108 (17)	−0.0077 (17)
O7	0.0292 (14)	0.0528 (18)	0.067 (2)	0.0032 (12)	0.0151 (14)	0.0009 (16)
C8	0.0303 (18)	0.0346 (19)	0.0349 (19)	−0.0006 (14)	0.0047 (15)	0.0048 (14)
C9	0.0286 (17)	0.046 (2)	0.0336 (19)	0.0007 (15)	0.0036 (15)	0.0009 (15)
C10	0.037 (2)	0.048 (2)	0.035 (2)	0.0035 (17)	0.0049 (16)	−0.0002 (17)
C11A	0.055 (2)	0.043 (2)	0.039 (2)	−0.0025 (18)	−0.0002 (18)	0.0000 (17)
N11B	0.055 (2)	0.043 (2)	0.039 (2)	−0.0025 (18)	−0.0002 (18)	0.0000 (17)
C12	0.037 (2)	0.050 (3)	0.048 (2)	−0.0095 (18)	−0.0029 (18)	0.0029 (19)
C13	0.0297 (19)	0.048 (2)	0.047 (2)	−0.0043 (16)	0.0057 (17)	0.0058 (18)
C15	0.0331 (17)	0.0352 (18)	0.0257 (16)	0.0025 (14)	0.0045 (13)	−0.0009 (14)
C16	0.0372 (19)	0.0332 (18)	0.0313 (17)	−0.0009 (15)	0.0079 (15)	−0.0007 (14)
C17	0.0360 (19)	0.038 (2)	0.0323 (18)	−0.0024 (15)	0.0063 (15)	−0.0016 (14)
N18A	0.0284 (10)	0.0371 (11)	0.0211 (9)	0.0016 (8)	−0.0013 (7)	−0.0038 (8)
C18B	0.0284 (10)	0.0371 (11)	0.0211 (9)	0.0016 (8)	−0.0013 (7)	−0.0038 (8)
C19	0.0344 (18)	0.0363 (19)	0.0381 (19)	0.0028 (15)	0.0025 (15)	0.0013 (15)
C20	0.0318 (18)	0.0329 (19)	0.041 (2)	−0.0005 (14)	0.0037 (15)	−0.0014 (15)
I1	0.03172 (15)	0.03684 (16)	0.03268 (16)	−0.00256 (9)	0.00260 (10)	−0.00114 (9)

Geometric parameters (Å, º) top

F1A—C11A	1.376 (5)	C10—C11A	1.365 (6)
C1—C2	1.378 (5)	C10—H10	0.9500
C1—C5	1.431 (5)	C11A—C12	1.375 (7)
C1—C8	1.472 (5)	C12—C13	1.378 (7)
C2—N3	1.328 (5)	C12—H12	0.9500
C2—C15	1.477 (5)	C13—H13	0.9500
N3—O4	1.383 (4)	C15—C16	1.383 (5)
N3—C6	1.444 (6)	C15—C20	1.393 (6)
O4—C5	1.400 (5)	C16—C17	1.382 (5)
C5—O7	1.208 (5)	C16—H16	0.9500
C6—H6A	0.9800	C17—N18A	1.336 (6)
C6—H6B	0.9800	C17—H17	0.9500
C6—H6C	0.9800	N18A—C19	1.334 (5)
C8—C13	1.392 (6)	N18A—H18A	0.8800
C8—C9	1.397 (6)	C19—C20	1.386 (5)
C9—C10	1.390 (6)	C19—H19	0.9500
C9—H9	0.9500	C20—H20	0.9500

C2—C1—C5	105.4 (3)	C10—C11A—C12	122.8 (4)
C2—C1—C8	129.2 (3)	C10—C11A—F1A	118.4 (4)
C5—C1—C8	125.1 (4)	C12—C11A—F1A	118.8 (4)
N3—C2—C1	111.3 (3)	C11A—C12—C13	118.5 (4)
N3—C2—C15	118.9 (3)	C11A—C12—H12	120.8
C1—C2—C15	129.6 (4)	C13—C12—H12	120.8
C2—N3—O4	108.8 (3)	C12—C13—C8	121.3 (4)
C2—N3—C6	134.4 (4)	C12—C13—H13	119.4
O4—N3—C6	116.8 (3)	C8—C13—H13	119.4
N3—O4—C5	107.6 (3)	C16—C15—C20	119.5 (3)
O7—C5—O4	117.8 (4)	C16—C15—C2	122.2 (4)
O7—C5—C1	135.3 (4)	C20—C15—C2	118.1 (3)
O4—C5—C1	106.9 (3)	C17—C16—C15	119.1 (4)
N3—C6—H6A	109.5	C17—C16—H16	120.4
N3—C6—H6B	109.5	C15—C16—H16	120.4
H6A—C6—H6B	109.5	N18A—C17—C16	120.5 (4)
N3—C6—H6C	109.5	N18A—C17—H17	119.7
H6A—C6—H6C	109.5	C16—C17—H17	119.7
H6B—C6—H6C	109.5	C19—N18A—C17	121.6 (3)
C13—C8—C9	118.2 (4)	C19—N18A—H18A	119.2
C13—C8—C1	120.4 (4)	C17—N18A—H18A	119.2
C9—C8—C1	121.3 (4)	N18A—C19—C20	120.7 (4)
C10—C9—C8	121.1 (4)	N18A—C19—H19	119.6
C10—C9—H9	119.5	C20—C19—H19	119.6
C8—C9—H9	119.5	C19—C20—C15	118.5 (4)
C11A—C10—C9	118.2 (4)	C19—C20—H20	120.7
C11A—C10—H10	120.9	C15—C20—H20	120.7
C9—C10—H10	120.9

C5—C1—C2—N3	0.7 (5)	C1—C8—C9—C10	177.6 (4)
C8—C1—C2—N3	−173.3 (4)	C8—C9—C10—C11A	−1.2 (6)
C5—C1—C2—C15	−173.3 (4)	C9—C10—C11A—C12	0.7 (7)
C8—C1—C2—C15	12.7 (7)	C9—C10—C11A—F1A	−177.8 (4)
C1—C2—N3—O4	0.6 (5)	C10—C11A—C12—C13	−0.1 (7)
C15—C2—N3—O4	175.3 (3)	F1A—C11A—C12—C13	178.4 (4)
C1—C2—N3—C6	178.3 (5)	C11A—C12—C13—C8	0.2 (7)
C15—C2—N3—C6	−7.0 (8)	C9—C8—C13—C12	−0.7 (6)
C2—N3—O4—C5	−1.7 (5)	C1—C8—C13—C12	−177.1 (4)
C6—N3—O4—C5	−179.9 (4)	N3—C2—C15—C16	60.6 (5)
N3—O4—C5—O7	−178.4 (4)	C1—C2—C15—C16	−125.8 (5)
N3—O4—C5—C1	2.1 (4)	N3—C2—C15—C20	−116.6 (4)
C2—C1—C5—O7	178.9 (5)	C1—C2—C15—C20	57.0 (6)
C8—C1—C5—O7	−6.8 (8)	C20—C15—C16—C17	−1.0 (5)
C2—C1—C5—O4	−1.7 (4)	C2—C15—C16—C17	−178.1 (3)
C8—C1—C5—O4	172.6 (3)	C15—C16—C17—N18A	0.5 (5)
C2—C1—C8—C13	−168.6 (4)	C16—C17—N18A—C19	−0.4 (5)
C5—C1—C8—C13	18.5 (6)	C17—N18A—C19—C20	0.7 (6)
C2—C1—C8—C9	15.1 (6)	N18A—C19—C20—C15	−1.2 (6)
C5—C1—C8—C9	−157.8 (4)	C16—C15—C20—C19	1.4 (6)
C13—C8—C9—C10	1.3 (6)	C2—C15—C20—C19	178.6 (4)

Experimental details

Crystal data
Chemical formula	C₁₅H₁₂FN₂O₂⁺·I⁻
M_r	398.17
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	193
a, b, c (Å)	10.2804 (4), 20.5895 (9), 7.4907 (3)
β (°)	96.8828 (14)
V (Å³)	1574.12 (11)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	2.05
Crystal size (mm)	0.52 × 0.20 × 0.08

Data collection
Diffractometer	Bruker APEXII CCD
Absorption correction	Multi-scan (APEX2; Bruker, 2006)
T_min, T_max	0.415, 0.853
No. of measured, independent and observed [I > 2σ(I)] reflections	27681, 3897, 3369
R_int	0.126
(sin θ/λ)_max (Å⁻¹)	0.668

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.040, 0.115, 1.07
No. of reflections	3897
No. of parameters	188
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	1.60, −0.51

Computer programs: APEX2 (Bruker, 2006), SIR92 (Altomare et al., 1994), SHELXL97 (Sheldrick, 1997), ORTEP (Johnson, 1968) and PLATON (Spek, 2003).

Acknowledgements

The authors thank the EU-Craft Programme, Project Macrocept (FP6), for funding.

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