Two 1,4-dihydro­pyridine derivatives with potential calcium-channel antagonist activity

The title compounds, benzyl 4-(3-chloro-2-fluoro­phenyl)-2-methyl-5-oxo-4,5,6,7-tetra­hydro-1H-cyclo­penta­[b]pyridine-3-carboxyl­ate, C₂₃H₁₉ClFNO₃, (I), and 3-pyridyl­methyl 4-[2-fluoro-3-(trifluoro­methyl)phenyl]-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexa­hydro­quinoline-3-carboxyl­ate, C₂₆H₂₄F₄N₂O₃, (II), belong to a class of 1,4-dihydro­pyridines whose members sometimes display calcium modulatory properties. The 1,4-dihydro­pyridine ring in each structure has a shallower than usual shallow-boat conformation and is nearly planar in (I). In each structure, the halogen-substituted benzene ring is oriented such that the halogen substituents are in a synperiplanar orientation with respect to the 1,4-dihydro­pyridine ring plane. The oxocyclo­pentene ring in (I) is planar, while the oxocyclo­hexene ring in (II) has a half-chair conformation, which is less commonly observed than the envelope conformation usually found in related compounds. In (I), the frequently observed inter­molecular N-H...O hydrogen bond between the amine group and the carbonyl O atom of the oxocyclo­pentene ring of a neighbouring mol­ecule links the mol­ecules into extended chains; there are no other significant inter­molecular inter­actions. By contrast, the amine group in (II) forms an N-H...N hydrogen bond with the pyridine ring N atom of a neighbouring mol­ecule. Additional C-H...O inter­actions complete a two-dimensional hydro­gen-bonded network. The halogen-substituted benzene ring has a weak intra­molecular [pi]-[pi] inter­action with the pyridine ring. A stronger [pi]-[pi] inter­action occurs between the 1,4-di­hydro­pyridine rings of centrosymmetrically related mol­ecules.

S1. Comment

Cardiovascular diseases include disorders of the heart and blood vessels, hypertension, peripheral artery disease, rheumatic heart disease, congenital heart disease and heart failure. Calcium-channel antagonists inhibit muscle contraction by blocking the influx of Ca²⁺ through calcium channels and are used as antianginal and antihypertensive drugs. 1,4-Dihydropyridine (1,4-DHP) derivatives are the most studied group and nifedipine is the prototype of calcium-channel antagonists (Triggle & Swamy, 1980; Janis & Triggle, 1984; Triggle, 1990, 2003; Şafak & Şimşek, 2006; Bülbül et al., 2009). Modifications to the nifedipine structure, such as replacing the ester moiety with various acyl analogues or fusing one of the carbonyl groups into the ring system, gives some active molecules (Şimşek et al., 2006; Gündüz et al., 2009). Following on from these structure–activity relationship studies and our experience in this area, we synthesized benzyl 4-(3-chloro-2-fluorophenyl)-2-methyl-5-oxo-4,5,6,7-tetrahydro-1H-cyclopenta[b]pyridine-3-carboxylate, (I), and 3-pyridylmethyl 4-[2-fluoro-3-(trifluoromethyl)phenyl]-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate, (II), and their calcium-channel modulatory activity was investigated on isolated rat ileum and thoracic artery. Compound (I) shows calcium-channel blocker activity in isolated rat ileum and rat thoracic artery, using nicardipine as a standard compound. Compound (II) also demonstrates calcium-channel blocker activity. The maximum relaxant responses (E_max) and pD₂ values of (II) and nifedipine were determined on isolated strips of rabbit gastric fundus smooth muscle (unpublished data).

Views of the asymmetric units of the structures of (I) and (II) are shown in Figs. 1 and 2, respectively. Most of the bond lengths and angles in (I) and (II) have normal values. There are small angular distortions about atom C2 and the ester C atom [C9 in (I), C10 in (II)] (Tables 1 and 3), which result from steric interactions between the methyl substituent at C2 and atom O1 of the ester substituent at C3 [O1···C8 in (I) and O1···C9 in (II) are both 2.847 (2) Å]. The presence of π-electron conjugation keeps the ester group at C3 almost coplanar with the endocyclic double bond [C2═C3—C9═O1 = -11.3 (3)° for (I) and C2═C3—C10═O1 = -5.6 (3)° for (II)] and prevents the ester group from rotating into a sterically more amenable orientation. These properties are consistent with those of related compounds (Linden et al., 2005, 2006).

The 1,4-DHP rings in (I) and (II) have very shallow boat conformations. In (I), the ring is almost completely planar, with atoms N1 and C4 lying just 0.0342 (18) and 0.0612 (19) Å, respectively, from the plane defined by atoms C2/C3/C4a/C7a. The corresponding displacements in (II) are 0.0296 (14) and 0.1004 (16) Å, respectively [atom C8a is in the position represented by C7a in (I)]. The conformations of 4-aryl-1,4-DHP rings have been discussed previously (Goldmann & Stoltefuss, 1991; Linden et al. 1998, 2002, 2005; Şimşek et al., 2000) and it is usual for the ring to have a shallow boat conformation, although considerable variation in the shallowness of the boat is evident. The displacement of atom C4 from the base of the boat in 1,4-DHP rings is frequently found to be around 0.30 Å (Şimşek et al., 2000). The deviations shown by atom N1 are generally smaller and spread fairly evenly over the range 0.00–0.19 Å (Şimşek et al., 2000; Linden et al., 2002). The deviations shown by atoms N1 in (I) and (II) fall well within this range, while those of C4 show that the C4 end of the boat is much flatter than normal. A completely planar 1,4-DHP ring was found in the structure of N,N-diethyl-2,6,6-trimethyl-4-(3-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxamide (Linden et al., 2002).

Another measure of the planarity of 1,4-DHP rings is the sum of the magnitudes of the six intraring torsion angles, P, around the ring (Fossheim et al., 1988). For (I) and (II), P is 20.0 (7) and 25.2 (7)°, respectively, which demonstrates that the boat conformations are indeed quite shallow. A mean value of 77 (2)° was found previously for 1,4-DHP rings (Linden et al., 2002), although the P values generally vary over a wide range from 4 to 130°. For nifedipine itself, P is 72° (Miyamae et al., 1986).

The planes of the 3-chloro-2-fluorophenyl ring in (I) and the 2-fluoro-3-(trifluoromethyl)phenyl ring in (II) lie in the usual synperiplanar orientation, which places the benzene-ring substituents above the C4—H bond rather than over the 1,4-DHP ring, which, because of the substituent in the 2-position of the phenyl ring, would be sterically unfavourable. The N1···C4—C17—C22 torsion angles are 10.9 (2) and 5.8 (2)° for (I) and (II), respectively. The corresponding torsion angles in related structures are clustered around 0° and rarely exceed ±30° (Linden et al., 2002). The observed orientation of the halophenyl ring brings the C22—H22 bond over the centre of the 1,4-DHP ring, and the distance from atom H22 to the centroid of the 1,4-DHP ring is just 2.81 Å in (I) and 2.67 Å in (II). The shorter distance for the latter is a consequence of the slightly deeper boat conformation of the 1,4-DHP ring, which displaces the halophenyl ring up higher and thereby points the C22—H22 bond more deeply into the centre of the 1,4-DHP ring.

The oxocyclopentene ring in (I) is almost planar, with a maximum deviation from the mean plane defined by the five ring atoms of 0.0292 (19) Å for atom C7a. The angle between the plane defined by the base of the 1,4-DHP ring boat (atoms C2/C3/C4a/C7a) and that of the oxocyclopentene ring is 5.05 (12)°, which indicates that the fused rings are essentially coplanar. The oxocyclohexene ring in (II) adopts a nearly ideal half-chair conformation twisted on the C6—C7 bond, with atoms C6 and C7 lying 0.289 (2) and 0.382 (2) Å, respectively, from the plane defined by the remaining four ring atoms, C4a/C5/C8/C8a. The ring-puckering parameters (Cremer & Pople, 1975) for this ring are Q = 0.4370 (19) Å, θ = 130.1 (2)° and ϕ₂ = 335.1 (3)° for the atom sequence C4a–C5–C6–C7–C8–C8a. The ideal values for a half-chair conformation in a six-membered ring are θ = 50° (or 180 - 50 = 130°) and ϕ₂ = (n × 60) + 30°, where n is an integer. Atom C7 of the ring flips down on the opposite side of the oxocyclohexene ring plane to the 2-fluoro-3-(trifluoromethyl)phenyl ring substituent of the adjacent 1,4-DHP ring. A half-chair conformation was also observed in the structure of methyl 4-(2,4-chlorophenyl)-2-methyl-7-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate monohydrate (Linden et al., 2006). More frequently, the oxocyclohexene ring in similar structures involving the 5-oxoquinoline or 1,8-dioxoacridine fragment adopts an envelope conformation, with atom C7 always being the out-of-plane atom, and the side of the oxocyclohexene ring to which C7 deviates is, in the majority, but not all, of these structures, opposite to that in (I) (Linden et al., 2002, 2005).

The angle between the plane of the 3-chloro-2-fluorophenyl ring and that of the phenyl ring of the ester substituent in (I) is 32.65 (10)°, which precludes any chance of there being a π–π interaction between these rings. There are also no other π–π interactions evident in the structure. In contrast, a weak π–π interaction may be present between the 2-fluoro-3-(trifluoromethyl)phenyl ring and the pyridyl ring in (II). The angle between the planes of these rings is 2.94 (8)°. The distance between the ring centroids is quite long at 4.0014 (10) Å, although the perpendicular distance from the pyridyl ring centroid to the plane of the other ring is 3.8258 (7) Å. The angle between these two vectors is 17.0°, which indicates a significant degree of offset of the two parallel rings. A stronger π–π interaction in (II) appears to exist between the 1,4-DHP rings of adjacent molecules related by a centre of inversion. The distance between the ring centroids of the molecules at (x, y, z) and (2 - x, -y, 2 - z) is 3.7634 (9) Å, while the perpendicular distance from the centroid of one ring to the plane of the other is 3.6037 (6) Å. The angle between these two vectors is 16.8° and the slippage of the centroids is 1.09 Å.

In compound (I), an intermolecular N—H···O hydrogen bond between the amine group and the carbonyl O atom of the oxocyclpentene ring of a neighbouring molecule (Table 2, Fig. 3) links the molecules into extended chains which run parallel to the [010] direction and can be described by a graph-set motif of C(6) (Bernstein et al., 1995). The same C(6) motif has been observed in the crystal structures of several other closely related 1,4-DHP compounds (Linden et al., 1998, 2002, 2004, 2005, 2006; Şimşek et al., 2000). There are no significant inter- or intramolecular C—H···X (X = O, N or halogen) interactions in the structure.

A more unusual hydrogen bond is present in the structure of (II). This time, the amine group forms an intermolecular N—H···N hydrogen bond with the pyridyl ring N atom of a neighbouring molecule (Table 4, Fig. 4). This interaction links the molecules into extended chains which run parallel to the [001] direction and can be described by a graph-set motif of C(10). Atom O5 of the oxocyclohexene ring this time acts as an acceptor of a weaker C—H···O hydrogen bond from atom C15—H of a neighbouring molecule. This interaction links the molecules into extended chains which run parallel to the [010] direction and can be described by a graph-set motif of C(12). A further C—H···O interaction between C7—H and ester atom O1 of another neighbouring molecule forms a centrosymmeteric R²₂(18) ring. The combination of all the hydrogen-bonding interactions in (II) leads to sheets of molecules which lie parallel to the (100) plane.

Related literature

For related literature, see: Bülbül et al. (2009); Bernstein et al. (1995); Cremer & Pople (1975); Fossheim et al. (1988); Gündüz et al. (2009); Goldmann & Stoltefuss (1991); Janis & Triggle (1984); Linden et al. (1998, 2002, 2004, 2005, 2006); Miyamae et al. (1986); Triggle (1990, 2003); Triggle & Swamy (1980); Şafak & Şimşek (2006); Şimşek et al. (2000, 2006, 2008).

S2. Experimental

Compounds (I) and (II) were prepared according to the method described by Şimşek et al. (2008) by refluxing the appropriate dicarbonyl compound, 2,3-disubstituted benzaldehyde, acetoacetate derivative and ammonium acetate in methanol for 8 h. After cooling, compound (I) was poured into ice–water. The obtained precipitate was crystallized from ethyl acetate to give diffraction quality crystals (yield 35%, m.p. 445 K). Analysis calculated for C₂₃H₁₉ClFNO₃: C 67.07, H 4.65, N 3.40%; found: C 66.67, H 4.67, N 3.40%. Compound (II) was obtained in a crystalline state suitable for crystallographic analysis after cooling the reaction mixture (yield 79%, m.p. 462 K). Analysis calculated for C₂₆H₂₄F₄N₂O₃: C 63.93, H 4.95, N 5.73%; found: C 63.76, H 4.86, N 5.86%. The structures of the compounds were elucidated by IR, ¹H NMR, ¹³C NMR and mass spectroscopy; the spectroscopic details are available in the archived CIF.

S3. Refinement

The amine H atoms were placed in the positions indicated by difference electron-density maps and their positions were allowed to refine together with individual isotropic displacement parameters. The methyl H atoms were constrained to an ideal geometry, with C—H = 0.98 Å and U_iso(H) = 1.5U_eq(C), but were allowed to rotate freely about the adjacent C—C bonds. All other H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms, with C—H = 0.95 (aromatic), 0.99 (methylene) or 1.00 Å (methine) and with U_iso(H) = 1.2U_eq(C).

Computing details

For both compounds, data collection: COLLECT (Nonius, 2000); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997); data reduction: DENZO-SMN and SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures

	Fig. 1. A view of the molecule of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. A view of the molecule of (II), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 3. A view, down the a axis, of the crystal packing in (I), showing the chains of molecules formed by the N—H···O hydrogen bonds (thin lines). Most H atoms have been omitted for clarity.
	Fig. 4. A view, down the b axis, of the crystal packing in (II), showing the chains of molecules formed by the N—H···N hydrogen bonds (thin lines). The sheets formed by the additional C—H···O interactions lie parallel to the (100) plane. Most H atoms have been omitted for clarity.

(I) benzyl 4-(3-chloro-2-fluorophenyl)-2-methyl-5-oxo-4,5,6,7-tetrahydro- 1H-cyclopenta[b]pyridine-3-carboxylate

Crystal data

C23H19ClFNO3	F(000) = 856
Mr = 411.86	Dx = 1.376 Mg m^−3
Monoclinic, P21/c	Melting point: 445 K
Hall symbol: -P 2ybc	Mo Kα radiation, λ = 0.71073 Å
a = 10.7944 (2) Å	Cell parameters from 26458 reflections
b = 13.5205 (3) Å	θ = 2.0–27.5°
c = 14.0573 (3) Å	µ = 0.23 mm^−1
β = 104.2378 (13)°	T = 160 K
V = 1988.58 (7) Å^3	Prism, colourless
Z = 4	0.30 × 0.28 × 0.15 mm

Data collection

Nonius KappaCCD area-detector diffractometer	4536 independent reflections
Radiation source: Nonius FR590 sealed tube generator	3193 reflections with I > 2σ(I)
Horizontally mounted graphite crystal monochromator	Rint = 0.076
Detector resolution: 9 pixels mm^-1	θmax = 27.5°, θmin = 2.1°
ϕ and ω scans with κ offsets	h = −13→13
Absorption correction: multi-scan (Blessing, 1995)	k = −17→17
Tmin = 0.914, Tmax = 0.974	l = −18→18
49390 measured reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.048	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.130	w = 1/[σ^2(Fo^2) + (0.0634P)^2 + 0.6774P] where P = (Fo^2 + 2Fc^2)/3
S = 1.03	(Δ/σ)max = 0.001
4536 reflections	Δρmax = 0.31 e Å^−3
268 parameters	Δρmin = −0.22 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0042 (10)

Special details

Experimental. Solvent used: ethyl acetate. Cooling device: Oxford Cryosystems Cryostream 700. Crystal mount: glued on a glass fibre. Mosaicity (°.): 0.489 (1). Frames collected: 335. Seconds exposure per frame: 44. Degrees rotation per frame: 2.0. Crystal-to-detector distance (mm): 30.0.

Spectroscopic data for (I): ¹H NMR (DMSO-d₆, δ, p.p.m.): 2.19–2.56 (4H, m, C6H₂, C7H₂), 2.32 (3H, s, 2CH₃), 4.89 ve 4.99 (2H, AB system, J_AB = 13.2 Hz, COOCH₂C₆H₅), 4.95 (1H, s, H4), 7.00–7.36 (8H, m, Ar—H), 9.88 (1H, s, N—H); ¹³C NMR (DMSO-d₆, δ, p.p.m.): 19.3, 24.2, 31.9, 33.8, 65.3, 102.4, 115.5, 119.8, 125.4, 127.9, 128.1, 128.5, 128.6, 129.6, 135.9, 136.1, 136.8, 148.1, 153.5, 155.9, 164.7, 166.6, 200.1; MS, m/z: 411 [M]⁺; analysis calculated for C₂₃H₁₉ClFNO₃: C 67.07, H 4.65, N 3.40%; found: C 66.67, H 4.67, N 3.40%.

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
Cl1	0.13943 (6)	0.58321 (4)	0.49870 (4)	0.05350 (19)
F1	0.34970 (10)	0.72106 (8)	0.51936 (9)	0.0432 (3)
O1	0.25302 (15)	1.07173 (10)	0.34374 (10)	0.0483 (4)
O2	0.30575 (12)	0.91264 (9)	0.37844 (9)	0.0364 (3)
O5	0.48877 (15)	0.79354 (10)	0.74898 (11)	0.0526 (4)
N1	0.40554 (15)	1.12420 (11)	0.65258 (12)	0.0355 (4)
H1	0.427 (2)	1.1843 (17)	0.6750 (16)	0.046 (6)*
C2	0.36240 (16)	1.11210 (13)	0.55130 (14)	0.0333 (4)
C3	0.34395 (16)	1.02069 (13)	0.51113 (13)	0.0313 (4)
C4	0.36952 (17)	0.92512 (12)	0.57140 (13)	0.0310 (4)
H4	0.4333	0.8847	0.5475	0.037*
C4a	0.42513 (17)	0.95092 (13)	0.67732 (14)	0.0341 (4)
C5	0.47776 (19)	0.88383 (14)	0.75576 (15)	0.0416 (5)
C6	0.5208 (2)	0.94317 (15)	0.85048 (16)	0.0525 (6)
H61	0.6136	0.9346	0.8790	0.063*
H62	0.4741	0.9217	0.8993	0.063*
C7	0.4898 (2)	1.05155 (14)	0.82098 (14)	0.0409 (5)
H71	0.4255	1.0788	0.8533	0.049*
H72	0.5676	1.0932	0.8378	0.049*
C7a	0.43754 (17)	1.04472 (13)	0.71201 (14)	0.0342 (4)
C8	0.3425 (2)	1.20956 (14)	0.49851 (16)	0.0426 (5)
H81	0.4187	1.2509	0.5212	0.064*
H82	0.2683	1.2431	0.5122	0.064*
H83	0.3277	1.1983	0.4277	0.064*
C9	0.29654 (17)	1.00822 (13)	0.40370 (14)	0.0348 (4)
C10	0.24343 (19)	0.88596 (15)	0.27759 (14)	0.0406 (5)
H101	0.2877	0.8284	0.2574	0.049*
H102	0.2496	0.9419	0.2336	0.049*
C11	0.10567 (19)	0.86079 (14)	0.26772 (13)	0.0384 (4)
C12	0.0718 (2)	0.76639 (15)	0.29089 (14)	0.0441 (5)
H12	0.1365	0.7184	0.3141	0.053*
C13	−0.0555 (2)	0.74141 (17)	0.28042 (16)	0.0515 (6)
H13	−0.0776	0.6766	0.2967	0.062*
C14	−0.1500 (2)	0.81036 (18)	0.24649 (16)	0.0528 (6)
H14	−0.2372	0.7930	0.2387	0.063*
C15	−0.1177 (2)	0.90494 (17)	0.22371 (18)	0.0562 (6)
H15	−0.1827	0.9527	0.2008	0.067*
C16	0.0097 (2)	0.93017 (16)	0.23432 (16)	0.0475 (5)
H16	0.0314	0.9952	0.2187	0.057*
C17	0.24775 (16)	0.86400 (13)	0.56100 (12)	0.0311 (4)
C18	0.24460 (17)	0.76446 (13)	0.53751 (13)	0.0326 (4)
C19	0.13622 (19)	0.70753 (13)	0.52915 (14)	0.0382 (4)
C20	0.02633 (19)	0.75014 (15)	0.54348 (14)	0.0423 (5)
H20	−0.0486	0.7115	0.5378	0.051*
C21	0.02598 (19)	0.84956 (15)	0.56617 (15)	0.0427 (5)
H21	−0.0496	0.8795	0.5758	0.051*
C22	0.13594 (18)	0.90603 (14)	0.57493 (14)	0.0363 (4)
H22	0.1346	0.9743	0.5907	0.044*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.0690 (4)	0.0309 (3)	0.0554 (3)	−0.0167 (2)	0.0053 (3)	−0.0035 (2)
F1	0.0425 (6)	0.0285 (6)	0.0575 (7)	0.0007 (5)	0.0105 (5)	−0.0041 (5)
O1	0.0616 (10)	0.0357 (7)	0.0406 (8)	0.0041 (7)	−0.0010 (7)	0.0060 (6)
O2	0.0396 (7)	0.0310 (7)	0.0355 (7)	−0.0004 (5)	0.0034 (6)	−0.0024 (5)
O5	0.0662 (10)	0.0274 (7)	0.0513 (9)	−0.0003 (6)	−0.0102 (7)	0.0065 (6)
N1	0.0384 (9)	0.0227 (8)	0.0416 (9)	−0.0003 (6)	0.0024 (7)	−0.0018 (6)
C2	0.0273 (9)	0.0275 (9)	0.0428 (11)	0.0000 (7)	0.0043 (7)	0.0017 (8)
C3	0.0267 (9)	0.0270 (9)	0.0382 (10)	−0.0009 (7)	0.0041 (7)	0.0034 (7)
C4	0.0300 (9)	0.0252 (9)	0.0358 (9)	−0.0004 (7)	0.0042 (7)	0.0004 (7)
C4a	0.0318 (9)	0.0272 (9)	0.0390 (10)	−0.0014 (7)	0.0003 (8)	0.0019 (7)
C5	0.0437 (11)	0.0307 (10)	0.0432 (11)	−0.0042 (8)	−0.0029 (9)	0.0033 (8)
C6	0.0653 (15)	0.0381 (11)	0.0423 (12)	−0.0047 (10)	−0.0089 (10)	0.0017 (9)
C7	0.0429 (11)	0.0351 (10)	0.0389 (11)	−0.0044 (8)	−0.0009 (9)	−0.0031 (8)
C7a	0.0298 (9)	0.0288 (9)	0.0409 (10)	−0.0021 (7)	0.0029 (8)	0.0000 (8)
C8	0.0443 (11)	0.0276 (10)	0.0516 (12)	0.0000 (8)	0.0036 (9)	0.0039 (8)
C9	0.0320 (9)	0.0287 (9)	0.0424 (11)	−0.0017 (7)	0.0065 (8)	0.0004 (8)
C10	0.0464 (11)	0.0407 (10)	0.0337 (10)	0.0000 (9)	0.0081 (8)	−0.0047 (8)
C11	0.0466 (11)	0.0371 (10)	0.0295 (9)	−0.0016 (8)	0.0056 (8)	−0.0061 (8)
C12	0.0543 (13)	0.0406 (11)	0.0340 (10)	−0.0030 (9)	0.0043 (9)	−0.0025 (8)
C13	0.0647 (15)	0.0477 (12)	0.0407 (12)	−0.0153 (11)	0.0106 (10)	−0.0048 (10)
C14	0.0484 (13)	0.0635 (15)	0.0470 (12)	−0.0120 (11)	0.0125 (10)	−0.0173 (11)
C15	0.0459 (13)	0.0533 (14)	0.0644 (15)	0.0040 (10)	0.0041 (11)	−0.0130 (11)
C16	0.0494 (13)	0.0380 (11)	0.0511 (13)	−0.0012 (9)	0.0049 (10)	−0.0048 (9)
C17	0.0324 (9)	0.0288 (9)	0.0290 (9)	−0.0022 (7)	0.0017 (7)	0.0012 (7)
C18	0.0347 (10)	0.0290 (9)	0.0316 (9)	−0.0007 (7)	0.0035 (7)	0.0008 (7)
C19	0.0476 (11)	0.0312 (10)	0.0319 (10)	−0.0106 (8)	0.0022 (8)	0.0023 (8)
C20	0.0392 (11)	0.0462 (11)	0.0394 (11)	−0.0126 (9)	0.0054 (8)	0.0069 (9)
C21	0.0365 (10)	0.0486 (12)	0.0441 (11)	−0.0007 (9)	0.0120 (9)	0.0068 (9)
C22	0.0377 (10)	0.0324 (10)	0.0384 (10)	−0.0009 (8)	0.0089 (8)	0.0020 (8)

Geometric parameters (Å, º)

Cl1—C19	1.7371 (19)	C8—H82	0.9800
F1—C18	1.356 (2)	C8—H83	0.9800
O1—C9	1.214 (2)	C10—C11	1.498 (3)
O2—C9	1.350 (2)	C10—H101	0.9900
O2—C10	1.457 (2)	C10—H102	0.9900
O5—C5	1.233 (2)	C11—C12	1.388 (3)
N1—C7a	1.353 (2)	C11—C16	1.391 (3)
N1—C2	1.395 (2)	C12—C13	1.388 (3)
N1—H1	0.88 (2)	C12—H12	0.9500
C2—C3	1.353 (2)	C13—C14	1.377 (3)
C2—C8	1.502 (2)	C13—H13	0.9500
C3—C9	1.480 (3)	C14—C15	1.384 (3)
C3—C4	1.533 (2)	C14—H14	0.9500
C4—C4a	1.503 (3)	C15—C16	1.389 (3)
C4—C17	1.529 (2)	C15—H15	0.9500
C4—H4	1.0000	C16—H16	0.9500
C4a—C7a	1.354 (2)	C17—C18	1.384 (2)
C4a—C5	1.433 (3)	C17—C22	1.391 (3)
C5—C6	1.526 (3)	C18—C19	1.381 (3)
C6—C7	1.537 (3)	C19—C20	1.377 (3)
C6—H61	0.9900	C20—C21	1.382 (3)
C6—H62	0.9900	C20—H20	0.9500
C7—C7a	1.499 (3)	C21—C22	1.391 (3)
C7—H71	0.9900	C21—H21	0.9500
C7—H72	0.9900	C22—H22	0.9500
C8—H81	0.9800
C9—O2—C10	116.52 (14)	O1—C9—C3	127.26 (17)
C2—N1—C7a	120.52 (16)	O2—C9—C3	110.36 (15)
C7a—N1—H1	120.4 (14)	O2—C10—C11	110.88 (15)
C2—N1—H1	117.8 (14)	O2—C10—H101	109.5
N1—C2—C3	120.74 (17)	C11—C10—H101	109.5
N1—C2—C8	111.90 (16)	O2—C10—H102	109.5
C3—C2—C8	127.37 (17)	C11—C10—H102	109.5
C2—C3—C4	123.47 (17)	H101—C10—H102	108.1
C2—C3—C9	120.55 (16)	C12—C11—C16	118.8 (2)
C9—C3—C4	115.98 (15)	C12—C11—C10	119.97 (18)
C4a—C4—C17	110.16 (15)	C16—C11—C10	121.20 (18)
C3—C4—C4a	109.00 (14)	C13—C12—C11	120.7 (2)
C17—C4—C3	111.67 (14)	C13—C12—H12	119.7
C4a—C4—H4	108.6	C11—C12—H12	119.7
C17—C4—H4	108.6	C14—C13—C12	120.1 (2)
C3—C4—H4	108.6	C14—C13—H13	119.9
C7a—C4a—C5	109.30 (17)	C12—C13—H13	119.9
C4—C4a—C7a	123.67 (16)	C13—C14—C15	119.9 (2)
C5—C4a—C4	126.98 (16)	C13—C14—H14	120.0
O5—C5—C4a	126.52 (19)	C15—C14—H14	120.0
O5—C5—C6	125.01 (18)	C14—C15—C16	120.1 (2)
C4a—C5—C6	108.46 (16)	C14—C15—H15	120.0
C5—C6—C7	105.45 (16)	C16—C15—H15	120.0
C5—C6—H61	110.7	C15—C16—C11	120.4 (2)
C7—C6—H61	110.7	C15—C16—H16	119.8
C5—C6—H62	110.7	C11—C16—H16	119.8
C7—C6—H62	110.7	C18—C17—C22	117.36 (16)
H61—C6—H62	108.8	C18—C17—C4	121.23 (16)
C7a—C7—C6	102.66 (16)	C22—C17—C4	121.41 (16)
C7a—C7—H71	111.2	F1—C18—C19	118.24 (16)
C6—C7—H71	111.2	F1—C18—C17	119.54 (16)
C7a—C7—H72	111.2	C19—C18—C17	122.20 (18)
C6—C7—H72	111.2	C20—C19—C18	119.77 (18)
H71—C7—H72	109.1	C20—C19—Cl1	120.72 (15)
N1—C7a—C4a	122.29 (17)	C18—C19—Cl1	119.50 (16)
N1—C7a—C7	123.83 (16)	C19—C20—C21	119.47 (18)
C4a—C7a—C7	113.88 (16)	C19—C20—H20	120.3
C2—C8—H81	109.5	C21—C20—H20	120.3
C2—C8—H82	109.5	C20—C21—C22	120.25 (19)
H81—C8—H82	109.5	C20—C21—H21	119.9
C2—C8—H83	109.5	C22—C21—H21	119.9
H81—C8—H83	109.5	C17—C22—C21	120.96 (18)
H82—C8—H83	109.5	C17—C22—H22	119.5
O1—C9—O2	122.37 (17)	C21—C22—H22	119.5
C7a—N1—C2—C3	4.3 (3)	C4—C3—C9—O1	168.60 (19)
C7a—N1—C2—C8	−175.30 (17)	C2—C3—C9—O2	169.66 (16)
N1—C2—C3—C9	179.20 (16)	C4—C3—C9—O2	−10.4 (2)
C8—C2—C3—C9	−1.3 (3)	C9—O2—C10—C11	−86.4 (2)
N1—C2—C3—C4	−0.7 (3)	O2—C10—C11—C12	−83.4 (2)
C8—C2—C3—C4	178.76 (18)	O2—C10—C11—C16	97.5 (2)
C2—C3—C4—C4a	−3.9 (2)	C16—C11—C12—C13	0.4 (3)
C9—C3—C4—C4a	176.21 (15)	C10—C11—C12—C13	−178.81 (18)
C2—C3—C4—C17	118.08 (19)	C11—C12—C13—C14	0.2 (3)
C9—C3—C4—C17	−61.8 (2)	C12—C13—C14—C15	−0.6 (3)
C17—C4—C4a—C7a	−117.1 (2)	C13—C14—C15—C16	0.5 (3)
C3—C4—C4a—C7a	5.7 (3)	C14—C15—C16—C11	0.1 (3)
C17—C4—C4a—C5	65.8 (2)	C12—C11—C16—C15	−0.5 (3)
C3—C4—C4a—C5	−171.32 (18)	C10—C11—C16—C15	178.67 (19)
C7a—C4a—C5—O5	−175.7 (2)	C4a—C4—C17—C18	−109.18 (18)
C4—C4a—C5—O5	1.7 (3)	C3—C4—C17—C18	129.55 (18)
C7a—C4a—C5—C6	3.4 (2)	C4a—C4—C17—C22	70.7 (2)
C4—C4a—C5—C6	−179.21 (19)	C3—C4—C17—C22	−50.6 (2)
O5—C5—C6—C7	178.7 (2)	C22—C17—C18—F1	177.37 (15)
C4a—C5—C6—C7	−0.4 (2)	C4—C17—C18—F1	−2.8 (2)
C5—C6—C7—C7a	−2.4 (2)	C22—C17—C18—C19	−0.8 (3)
C2—N1—C7a—C4a	−2.4 (3)	C4—C17—C18—C19	179.04 (16)
C2—N1—C7a—C7	177.36 (17)	F1—C18—C19—C20	−177.59 (16)
C5—C4a—C7a—N1	174.51 (17)	C17—C18—C19—C20	0.6 (3)
C4—C4a—C7a—N1	−3.0 (3)	F1—C18—C19—Cl1	1.4 (2)
C5—C4a—C7a—C7	−5.3 (2)	C17—C18—C19—Cl1	179.62 (14)
C4—C4a—C7a—C7	177.20 (17)	C18—C19—C20—C21	0.0 (3)
C6—C7—C7a—N1	−175.00 (19)	Cl1—C19—C20—C21	−179.01 (15)
C6—C7—C7a—C4a	4.8 (2)	C19—C20—C21—C22	−0.3 (3)
C10—O2—C9—O1	−8.9 (3)	C18—C17—C22—C21	0.5 (3)
C10—O2—C9—C3	170.15 (15)	C4—C17—C22—C21	−179.42 (17)
C2—C3—C9—O1	−11.3 (3)	C20—C21—C22—C17	0.1 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O5^i	0.88 (2)	1.92 (2)	2.772 (2)	163 (2)

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

(II) 3-pyridylmethyl 4-[2-fluoro-3-(trifluoromethyl)phenyl]-2,6,6-trimethyl-5- oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate

Crystal data

C26H24F4N2O3	F(000) = 1016
Mr = 488.48	Dx = 1.411 Mg m^−3
Monoclinic, P21/c	Melting point: 462 K
Hall symbol: -P 2ybc	Mo Kα radiation, λ = 0.71073 Å
a = 11.3696 (2) Å	Cell parameters from 5555 reflections
b = 9.2177 (2) Å	θ = 2.0–27.5°
c = 21.9577 (3) Å	µ = 0.11 mm^−1
β = 92.5683 (11)°	T = 160 K
V = 2298.89 (7) Å^3	Prism, colourless
Z = 4	0.25 × 0.25 × 0.25 mm

Data collection

Nonius KappaCCD area-detector diffractometer	3791 reflections with I > 2σ(I)
Radiation source: Nonius FR590 sealed tube generator	Rint = 0.056
Horizontally mounted graphite crystal monochromator	θmax = 27.5°, θmin = 2.4°
Detector resolution: 9 pixels mm^-1	h = 0→14
ϕ and ω scans with κ offsets	k = 0→11
49934 measured reflections	l = −28→28
5242 independent reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.049	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.133	w = 1/[σ^2(Fo^2) + (0.0602P)^2 + 0.8787P] where P = (Fo^2 + 2Fc^2)/3
S = 1.03	(Δ/σ)max = 0.002
5242 reflections	Δρmax = 0.29 e Å^−3
324 parameters	Δρmin = −0.27 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0058 (10)

Special details

Experimental. Solvent used: MeOH. Cooling device: Oxford Cryosystems Cryostream 700. Crystal mount: glued on a glass fibre. Mosaicity (°.): 0.364 (1). Frames collected: 418. Seconds exposure per frame: 35. Degrees rotation per frame: 1.6. Crystal-to-detector distance (mm): 33.0.

Spectroscopic data for (II): ¹H NMR (DMSO-d₆, δ, p.p.m.): 0.80 (3H, s, 6CH₃), 0.95 (3H, s, 6CH₃), 1.62–1.75 (2H, m, C7H₂), 2 27 (3H, s, 2CH₃), 2.45–2.55 (2H, m, C8H₂), 5.02 (2H, s, COOCH₂) 5.09 (H, s, H4), 7.16–8.49 (7H, m, Ar—H), 9.29 (1H, s, N—H); ¹³C NMR (DMSO-d₆, δ, p.p.m.): 18.4, 22.8, 24.1, 24.6, 31.2, 33.9, 40.1, 62.5, 100.9, 108.2, 115.6, 121.5, 123.2, 124.1, 124.3, 124.6, 132.0, 135.5, 136.6, 147.0, 148.9, 150.0, 154.4, 157.0, 166.1, 199.1; MS, m/z: 488 [M]⁺; analysis calculated for C₂₆H₂₄F₄N₂O₃: C 63.93, H 4.95, N 5.73%; found: C 63.76, H 4.86, N 5.86%.

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
F1	0.84064 (8)	−0.04342 (11)	0.78676 (4)	0.0327 (3)
F2	0.76012 (11)	0.07236 (13)	0.67323 (5)	0.0479 (3)
F3	0.57115 (12)	0.07200 (16)	0.66836 (5)	0.0649 (4)
F4	0.66626 (10)	−0.11777 (13)	0.69767 (5)	0.0471 (3)
O1	1.00677 (13)	0.36800 (15)	0.92933 (6)	0.0459 (4)
O2	0.97873 (10)	0.19983 (13)	0.85604 (5)	0.0294 (3)
O5	0.76265 (12)	−0.25272 (14)	0.87921 (5)	0.0388 (3)
N1	0.82672 (13)	0.06930 (15)	1.04343 (6)	0.0285 (3)
H1	0.8207 (17)	0.088 (2)	1.0836 (10)	0.042 (6)*
N2	0.81822 (14)	0.40666 (17)	0.67975 (6)	0.0355 (4)
C2	0.88859 (14)	0.16873 (18)	1.01005 (7)	0.0267 (4)
C3	0.90353 (14)	0.14671 (17)	0.94996 (7)	0.0252 (4)
C4	0.84801 (14)	0.01834 (17)	0.91543 (7)	0.0236 (4)
H4	0.9104	−0.0334	0.8932	0.028*
C4a	0.79225 (14)	−0.08699 (17)	0.95867 (7)	0.0251 (4)
C5	0.74269 (15)	−0.21921 (18)	0.93182 (7)	0.0284 (4)
C6	0.65763 (16)	−0.30763 (19)	0.96873 (8)	0.0327 (4)
C7	0.70064 (18)	−0.3068 (2)	1.03576 (8)	0.0371 (4)
H71	0.6420	−0.3573	1.0602	0.044*
H72	0.7754	−0.3617	1.0400	0.044*
C8	0.72048 (17)	−0.15439 (19)	1.06152 (8)	0.0329 (4)
H81	0.6435	−0.1111	1.0705	0.039*
H82	0.7679	−0.1611	1.1004	0.039*
C8a	0.78230 (14)	−0.05704 (18)	1.01853 (7)	0.0266 (4)
C9	0.93265 (16)	0.29567 (19)	1.04767 (8)	0.0331 (4)
H91	1.0148	0.2789	1.0612	0.050*
H92	0.8845	0.3065	1.0833	0.050*
H93	0.9273	0.3842	1.0230	0.050*
C10	0.96797 (15)	0.25103 (19)	0.91362 (7)	0.0288 (4)
C11	1.02469 (15)	0.2990 (2)	0.81130 (8)	0.0329 (4)
H111	1.0740	0.2449	0.7830	0.039*
H112	1.0745	0.3735	0.8322	0.039*
C12	0.92407 (15)	0.37076 (19)	0.77618 (7)	0.0295 (4)
C13	0.90662 (16)	0.34823 (19)	0.71382 (8)	0.0320 (4)
H13	0.9608	0.2876	0.6942	0.038*
C14	0.74214 (17)	0.4893 (2)	0.70837 (8)	0.0370 (4)
H14	0.6768	0.5281	0.6853	0.044*
C15	0.75297 (18)	0.5218 (2)	0.76998 (8)	0.0414 (5)
H15	0.6977	0.5833	0.7884	0.050*
C16	0.84592 (17)	0.4626 (2)	0.80393 (8)	0.0378 (5)
H16	0.8565	0.4846	0.8461	0.045*
C17	0.75277 (14)	0.07161 (17)	0.86937 (7)	0.0244 (4)
C18	0.75147 (14)	0.03566 (18)	0.80804 (7)	0.0251 (4)
C19	0.66275 (15)	0.07867 (19)	0.76650 (7)	0.0302 (4)
C20	0.57201 (15)	0.1645 (2)	0.78666 (8)	0.0348 (4)
H20	0.5107	0.1959	0.7589	0.042*
C21	0.57156 (16)	0.2039 (2)	0.84752 (8)	0.0358 (4)
H21	0.5103	0.2637	0.8616	0.043*
C22	0.66017 (15)	0.15640 (18)	0.88786 (8)	0.0292 (4)
H22	0.6575	0.1827	0.9296	0.035*
C23	0.66531 (16)	0.0279 (2)	0.70195 (8)	0.0366 (4)
C24	0.53644 (17)	−0.2346 (2)	0.95947 (9)	0.0435 (5)
H241	0.5416	−0.1337	0.9734	0.065*
H242	0.4786	−0.2868	0.9830	0.065*
H243	0.5119	−0.2367	0.9161	0.065*
C25	0.65245 (19)	−0.4635 (2)	0.94527 (9)	0.0438 (5)
H251	0.6287	−0.4635	0.9018	0.066*
H252	0.5951	−0.5187	0.9679	0.066*
H253	0.7303	−0.5085	0.9510	0.066*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
F1	0.0331 (5)	0.0419 (6)	0.0232 (5)	0.0073 (5)	0.0029 (4)	−0.0058 (4)
F2	0.0625 (8)	0.0544 (7)	0.0275 (6)	−0.0113 (6)	0.0083 (5)	0.0003 (5)
F3	0.0632 (8)	0.0935 (11)	0.0356 (7)	0.0202 (7)	−0.0232 (6)	−0.0061 (7)
F4	0.0613 (8)	0.0436 (7)	0.0358 (6)	−0.0128 (6)	−0.0034 (5)	−0.0099 (5)
O1	0.0698 (10)	0.0377 (8)	0.0304 (7)	−0.0250 (7)	0.0034 (6)	−0.0029 (6)
O2	0.0348 (6)	0.0319 (7)	0.0215 (6)	−0.0035 (5)	0.0029 (5)	0.0031 (5)
O5	0.0565 (8)	0.0343 (7)	0.0262 (7)	−0.0115 (6)	0.0077 (6)	−0.0072 (5)
N1	0.0404 (8)	0.0273 (8)	0.0179 (7)	−0.0053 (6)	0.0036 (6)	−0.0024 (6)
N2	0.0450 (9)	0.0380 (9)	0.0234 (7)	0.0017 (7)	0.0020 (7)	0.0014 (6)
C2	0.0310 (9)	0.0243 (9)	0.0245 (8)	−0.0002 (7)	−0.0014 (7)	0.0008 (7)
C3	0.0285 (8)	0.0236 (9)	0.0233 (8)	−0.0012 (7)	−0.0003 (7)	−0.0001 (6)
C4	0.0274 (8)	0.0233 (8)	0.0200 (8)	−0.0012 (7)	0.0010 (6)	−0.0007 (6)
C4a	0.0299 (9)	0.0230 (9)	0.0225 (8)	−0.0004 (7)	0.0017 (7)	0.0004 (6)
C5	0.0347 (9)	0.0270 (9)	0.0232 (8)	−0.0011 (7)	0.0000 (7)	−0.0018 (7)
C6	0.0416 (10)	0.0275 (9)	0.0292 (9)	−0.0089 (8)	0.0033 (8)	−0.0021 (7)
C7	0.0512 (11)	0.0301 (10)	0.0304 (9)	−0.0090 (8)	0.0078 (8)	0.0014 (8)
C8	0.0443 (10)	0.0311 (10)	0.0235 (8)	−0.0071 (8)	0.0042 (7)	0.0002 (7)
C8a	0.0321 (9)	0.0253 (9)	0.0224 (8)	−0.0005 (7)	0.0006 (7)	0.0000 (7)
C9	0.0450 (10)	0.0285 (9)	0.0257 (9)	−0.0050 (8)	−0.0005 (8)	−0.0036 (7)
C10	0.0325 (9)	0.0309 (10)	0.0227 (8)	−0.0046 (8)	−0.0024 (7)	0.0007 (7)
C11	0.0344 (9)	0.0390 (10)	0.0256 (9)	−0.0056 (8)	0.0052 (7)	0.0055 (8)
C12	0.0342 (9)	0.0293 (9)	0.0250 (8)	−0.0066 (7)	0.0034 (7)	0.0032 (7)
C13	0.0384 (10)	0.0321 (10)	0.0259 (9)	−0.0018 (8)	0.0047 (7)	0.0001 (7)
C14	0.0440 (11)	0.0387 (11)	0.0284 (9)	0.0054 (9)	0.0021 (8)	0.0057 (8)
C15	0.0513 (12)	0.0430 (11)	0.0306 (10)	0.0130 (9)	0.0080 (9)	0.0013 (8)
C16	0.0497 (11)	0.0417 (11)	0.0222 (9)	0.0029 (9)	0.0031 (8)	−0.0010 (8)
C17	0.0257 (8)	0.0231 (8)	0.0246 (8)	−0.0023 (7)	0.0029 (7)	0.0008 (6)
C18	0.0248 (8)	0.0263 (9)	0.0243 (8)	0.0002 (7)	0.0019 (7)	−0.0013 (7)
C19	0.0316 (9)	0.0333 (10)	0.0254 (9)	−0.0034 (7)	−0.0024 (7)	0.0015 (7)
C20	0.0300 (9)	0.0387 (11)	0.0352 (10)	0.0023 (8)	−0.0044 (7)	0.0035 (8)
C21	0.0307 (9)	0.0376 (10)	0.0393 (10)	0.0070 (8)	0.0032 (8)	−0.0017 (8)
C22	0.0325 (9)	0.0285 (9)	0.0269 (9)	−0.0006 (7)	0.0046 (7)	−0.0023 (7)
C23	0.0385 (10)	0.0440 (12)	0.0267 (9)	−0.0011 (9)	−0.0062 (8)	0.0009 (8)
C24	0.0410 (11)	0.0463 (12)	0.0435 (11)	−0.0095 (9)	0.0048 (9)	−0.0025 (9)
C25	0.0621 (13)	0.0311 (10)	0.0388 (11)	−0.0148 (9)	0.0089 (10)	−0.0034 (8)

Geometric parameters (Å, º)

F1—C18	1.3491 (18)	C8—H82	0.9900
F2—C23	1.337 (2)	C9—H91	0.9800
F3—C23	1.336 (2)	C9—H92	0.9800
F4—C23	1.346 (2)	C9—H93	0.9800
O1—C10	1.209 (2)	C11—C12	1.504 (3)
O2—C10	1.360 (2)	C11—H111	0.9900
O2—C11	1.456 (2)	C11—H112	0.9900
O5—C5	1.2269 (19)	C12—C16	1.388 (3)
N1—C8a	1.373 (2)	C12—C13	1.390 (2)
N1—C2	1.385 (2)	C13—H13	0.9500
N1—H1	0.90 (2)	C14—C15	1.386 (3)
N2—C14	1.331 (2)	C14—H14	0.9500
N2—C13	1.339 (2)	C15—C16	1.378 (3)
C2—C3	1.353 (2)	C15—H15	0.9500
C2—C9	1.505 (2)	C16—H16	0.9500
C3—C10	1.466 (2)	C17—C18	1.386 (2)
C3—C4	1.527 (2)	C17—C22	1.387 (2)
C4—C4a	1.517 (2)	C18—C19	1.387 (2)
C4—C17	1.529 (2)	C19—C20	1.388 (3)
C4—H4	1.0000	C19—C23	1.494 (2)
C4a—C8a	1.353 (2)	C20—C21	1.385 (3)
C4a—C5	1.456 (2)	C20—H20	0.9500
C5—C6	1.525 (2)	C21—C22	1.383 (2)
C6—C25	1.527 (3)	C21—H21	0.9500
C6—C7	1.530 (2)	C22—H22	0.9500
C6—C24	1.539 (3)	C24—H241	0.9800
C7—C8	1.527 (2)	C24—H242	0.9800
C7—H71	0.9900	C24—H243	0.9800
C7—H72	0.9900	C25—H251	0.9800
C8—C8a	1.500 (2)	C25—H252	0.9800
C8—H81	0.9900	C25—H253	0.9800
C10—O2—C11	117.35 (13)	C12—C11—H111	109.8
C2—N1—C8a	122.48 (14)	O2—C11—H112	109.8
C8a—N1—H1	120.6 (13)	C12—C11—H112	109.8
C2—N1—H1	116.8 (13)	H111—C11—H112	108.2
C14—N2—C13	116.99 (15)	C16—C12—C13	117.24 (17)
N1—C2—C3	120.37 (15)	C16—C12—C11	122.03 (15)
N1—C2—C9	112.87 (14)	C13—C12—C11	120.73 (16)
C3—C2—C9	126.76 (15)	N2—C13—C12	124.10 (17)
C2—C3—C4	122.23 (14)	N2—C13—H13	117.9
C2—C3—C10	121.32 (15)	C12—C13—H13	117.9
C10—C3—C4	116.33 (13)	N2—C14—C15	123.60 (18)
C3—C4—C4a	111.13 (12)	N2—C14—H14	118.2
C4a—C4—C17	108.44 (13)	C15—C14—H14	118.2
C3—C4—C17	110.14 (13)	C16—C15—C14	118.36 (18)
C4a—C4—H4	109.0	C16—C15—H15	120.8
C3—C4—H4	109.0	C14—C15—H15	120.8
C17—C4—H4	109.0	C15—C16—C12	119.62 (16)
C8a—C4a—C5	121.10 (15)	C15—C16—H16	120.2
C4—C4a—C8a	122.22 (15)	C12—C16—H16	120.2
C5—C4a—C4	116.57 (13)	C18—C17—C22	116.36 (15)
O5—C5—C4a	120.49 (15)	C18—C17—C4	122.84 (14)
O5—C5—C6	120.95 (15)	C22—C17—C4	120.78 (14)
C4a—C5—C6	118.37 (14)	F1—C18—C17	119.35 (14)
C5—C6—C25	109.84 (14)	F1—C18—C19	117.53 (14)
C5—C6—C7	108.99 (14)	C17—C18—C19	123.11 (15)
C25—C6—C7	109.59 (15)	C18—C19—C20	118.82 (15)
C5—C6—C24	106.34 (15)	C18—C19—C23	119.33 (16)
C25—C6—C24	110.27 (16)	C20—C19—C23	121.82 (16)
C7—C6—C24	111.75 (15)	C21—C20—C19	119.49 (16)
C8—C7—C6	113.36 (15)	C21—C20—H20	120.3
C8—C7—H71	108.9	C19—C20—H20	120.3
C6—C7—H71	108.9	C22—C21—C20	120.05 (16)
C8—C7—H72	108.9	C22—C21—H21	120.0
C6—C7—H72	108.9	C20—C21—H21	120.0
H71—C7—H72	107.7	C21—C22—C17	122.15 (16)
C8a—C8—C7	112.51 (14)	C21—C22—H22	118.9
C8a—C8—H81	109.1	C17—C22—H22	118.9
C7—C8—H81	109.1	F3—C23—F2	106.84 (15)
C8a—C8—H82	109.1	F3—C23—F4	105.87 (15)
C7—C8—H82	109.1	F2—C23—F4	105.27 (15)
H81—C8—H82	107.8	F3—C23—C19	112.29 (16)
N1—C8a—C4a	120.97 (15)	F2—C23—C19	113.69 (15)
C4a—C8a—C8	123.46 (15)	F4—C23—C19	112.27 (15)
N1—C8a—C8	115.55 (14)	C6—C24—H241	109.5
C2—C9—H91	109.5	C6—C24—H242	109.5
C2—C9—H92	109.5	H241—C24—H242	109.5
H91—C9—H92	109.5	C6—C24—H243	109.5
C2—C9—H93	109.5	H241—C24—H243	109.5
H91—C9—H93	109.5	H242—C24—H243	109.5
H92—C9—H93	109.5	C6—C25—H251	109.5
O1—C10—O2	121.85 (15)	C6—C25—H252	109.5
O2—C10—C3	110.26 (14)	H251—C25—H252	109.5
O1—C10—C3	127.89 (15)	C6—C25—H253	109.5
O2—C11—C12	109.54 (13)	H251—C25—H253	109.5
O2—C11—H111	109.8	H252—C25—H253	109.5
C8a—N1—C2—C3	2.7 (3)	C4—C3—C10—O1	170.57 (18)
C8a—N1—C2—C9	−177.69 (15)	C2—C3—C10—O2	175.42 (15)
N1—C2—C3—C10	179.55 (15)	C4—C3—C10—O2	−8.4 (2)
C9—C2—C3—C10	−0.1 (3)	C10—O2—C11—C12	−94.95 (17)
N1—C2—C3—C4	3.6 (2)	O2—C11—C12—C16	64.3 (2)
C9—C2—C3—C4	−175.97 (16)	O2—C11—C12—C13	−116.40 (17)
C2—C3—C4—C4a	−8.2 (2)	C14—N2—C13—C12	−1.1 (3)
C10—C3—C4—C4a	175.67 (14)	C16—C12—C13—N2	−1.6 (3)
C2—C3—C4—C17	111.96 (17)	C11—C12—C13—N2	179.02 (16)
C10—C3—C4—C17	−64.14 (18)	C13—N2—C14—C15	2.8 (3)
C3—C4—C4a—C8a	7.6 (2)	N2—C14—C15—C16	−1.6 (3)
C17—C4—C4a—C8a	−113.57 (17)	C14—C15—C16—C12	−1.3 (3)
C3—C4—C4a—C5	−176.18 (14)	C13—C12—C16—C15	2.8 (3)
C17—C4—C4a—C5	62.62 (18)	C11—C12—C16—C15	−177.87 (18)
C8a—C4a—C5—O5	−172.37 (17)	C4a—C4—C17—C18	−111.88 (17)
C4—C4a—C5—O5	11.4 (2)	C3—C4—C17—C18	126.32 (16)
C8a—C4a—C5—C6	12.6 (2)	C4a—C4—C17—C22	66.23 (19)
C4—C4a—C5—C6	−163.60 (15)	C3—C4—C17—C22	−55.57 (19)
O5—C5—C6—C25	26.3 (2)	C22—C17—C18—F1	178.27 (14)
C4a—C5—C6—C25	−158.75 (16)	C4—C17—C18—F1	−3.5 (2)
O5—C5—C6—C7	146.37 (17)	C22—C17—C18—C19	−0.9 (2)
C4a—C5—C6—C7	−38.7 (2)	C4—C17—C18—C19	177.26 (16)
O5—C5—C6—C24	−93.0 (2)	F1—C18—C19—C20	−177.74 (15)
C4a—C5—C6—C24	81.94 (18)	C17—C18—C19—C20	1.5 (3)
C5—C6—C7—C8	54.0 (2)	F1—C18—C19—C23	4.1 (2)
C25—C6—C7—C8	174.22 (16)	C17—C18—C19—C23	−176.66 (16)
C24—C6—C7—C8	−63.2 (2)	C18—C19—C20—C21	−0.5 (3)
C6—C7—C8—C8a	−43.5 (2)	C23—C19—C20—C21	177.54 (17)
C5—C4a—C8a—N1	−178.47 (15)	C19—C20—C21—C22	−0.8 (3)
C4—C4a—C8a—N1	−2.5 (3)	C20—C21—C22—C17	1.4 (3)
C5—C4a—C8a—C8	−0.3 (3)	C18—C17—C22—C21	−0.5 (2)
C4—C4a—C8a—C8	175.75 (15)	C4—C17—C22—C21	−178.76 (16)
C2—N1—C8a—C4a	−3.3 (3)	C18—C19—C23—F3	176.73 (16)
C2—N1—C8a—C8	178.38 (15)	C20—C19—C23—F3	−1.3 (3)
C7—C8—C8a—C4a	15.9 (3)	C18—C19—C23—F2	−61.8 (2)
C7—C8—C8a—N1	−165.79 (15)	C20—C19—C23—F2	120.12 (19)
C11—O2—C10—O1	−8.1 (2)	C18—C19—C23—F4	57.6 (2)
C11—O2—C10—C3	170.96 (13)	C20—C19—C23—F4	−120.51 (19)
C2—C3—C10—O1	−5.6 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···N2^i	0.90 (2)	2.11 (2)	3.0073 (19)	169.5 (19)
C7—H72···O1^ii	0.99	2.54	3.427 (3)	149
C15—H15···O5^iii	0.95	2.58	3.172 (2)	120

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