N,N-Diethyl-2,6,6-trimethyl-4-(3-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxamide

The title compound, C₂₃H₂₉N₃O₄, has potential calcium modulatory properties. The conformation of the 1,4-di­hydro­pyridine ring is unusual in that it is planar, instead of the usual shallow boat. The 3-nitro­phenyl substituent is in the synperiplanar orientation with respect to the di­hydro­pyridine ring plane. The oxo­cyclo­hexene ring has a distorted envelope conformation, with the out-of-plane atom being disordered on opposite sides of the ring plane. The mol­ecules are linked into chains by intermolecular hydrogen bonds.

S1. Comment

Calcium-channel blocking agents inhibit smooth muscle contraction and are used as antihypertensive drugs (Flaim & Zelic, 1982; Janis & Triggle, 1984). Although these drugs are represented by a diverse group of compounds, 1,4-dihydropyridine (1,4-DHP) derivatives are a well known class. Nifedipine is the most popular 1,4-DHP-based drug and many modifications are being made to the nifedipine molecule in attempts to obtain more active drugs. Active compounds have been produced by the introduction of the 1,4-DHP moiety in condensed systems, and the replacement of the ester group in the nifedipine molecule with various carbonyl-containing groups, such as amides, nitriles and the acetyl group (Loev et al., 1974; Rose, 1989, 1990a,b; Rose & Dräger, 1992; Ogawa et al., 1993; Şafak et al., 1995). Those derivatives that contain a chiral centre at the 4-position of the 1,4-DHP ring of the molecule also possess calcium modulatory properties. The activity depends on an axial aromatic ring, the plane of which bisects the N1···C4 axis of the 1,4-DHP ring, as well as on the conformation of the 1,4-DHP ring itself, which is usually that of a shallow boat (Goldmann & Stoltefuss, 1991; Linden et al., 1998). The activity may be agonist or antagonist and varies with stereochemical changes in the molecule. The title compound, (I), has been prepared as a further potentially active 1,4-DHP derivative. Its structure was confirmed by IR, ¹H NMR, ¹³C NMR and elemental analyses, but the determination of its three-dimensional conformation is important in order to obtain further insight into the structure-activity relationships of these compounds. \sch

The 1,4-DHP ring in the structure of (I) is planar; the r.m.s. deviation of the six atoms of the ring from their mean plane is 0.010 Å and the maximum deviation is 0.016 (2) Å for C2. The conformations of 4-aryl-1,4-DHP rings have been discussed previously (Goldmann & Stoltefuss, 1991; Linden et al. 1998; Şimşek et al., 2000) and it is usual for the ring to have a shallow boat conformation. In (I), even when atoms N1 and C4 are excluded from the plane calculation, they deviate from the mean plane defined by the other four atoms by 0.022 (4) and -0.014 (5) Å, respectively, which demonstrates that even the shallowest of boat conformations is not present. The Cambridge Structural Database (CSD, April 2002 release; Allen & Kennard, 1993) currently contains 124 entries with the 4-aryl-1,4-DHP moiety, excluding 4,4-disubstituted derivatives. Even though these entries show that there can be considerable variation in the shallowness of the boat conformation, only three structures have an essentially planar 1,4-DHP ring (Pastor et al., 1994; Duque et al., 2000; Low et al., 2001). A comparison of these three structures with (I) failed to reveal any obvious similarity in the substituents, either on the 1,4-DHP ring or on the 4-aryl group, that might explain the tendency for planarity.

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 compound (I), P is 10 (1)°. The value of P for the 124 entries in the CSD ranges from 4 to 130°, although only four structures have P < 28° and the mean value is 77 (2)°. For nifedipine itself, P is 72° (Miyamae et al., 1986). Only one other reported structure has a smaller value of P than that for (I) (4.4°; Duque et al., 2000). Such a severe flattening might have significant implications for the pharmacological potency of (I) as a calcium channel antagonist, because it has been suggested (Fossheim et al., 1982, 1988) that the most active compounds in the nifedipine and nisoldipine series possess the shallowest boat conformations. The calcium modulatory activity of (I) will be reported later.

The plane of the 3-nitrophenyl ring of (I) is almost parallel to the N1···C4 axis, with an N1···C4—C15—C20 torsion angle of -12.3 (4)°. This is quite normal; the corresponding torsion angle in the 124 related structures in the CSD is clustered around 0° and rarely exceeds ±30°. The nitro substituent lies above the C4—H bond in a synperiplanar orientation, and not over the 1,4-DHP ring. The carbonyl group of the amide substituent at C3 is far from being coplanar with the 1,4-DHP ring and the C2═C3—C10═O10 torsion angle is 116.8 (3)°. This indicates that there is no significant π-electron conjugation between the C2═C3 bond and the carbonyl group. Instead, this carbonyl group conjugates with the lone electron pair on atom N10, in the normal fashion of amides, which gives rise to a planar geometry about N10. The CSD contains entries for seven structures that have an amide substituent at one or both of the 1,4-DHP ring C atoms adjacent to C4, and each of these structures shows a similar lack of coplanarity between the amide C═O and the ring C═C bonds. Conversely, coplanarity prevails when the carbonyl group is not part of an amide group (114 structures in the CSD).

The oxocyclohexene ring in compound (I) is disordered over two conformations. Each conformation is that of a slightly distorted envelope, with atom C7 or C7A as the envelope flap. The major conformation exists in 69.8 (6)% of the molecules and has the envelope flap, C7, on the opposite side of the fused ring plane to the 3-nitrophenyl substituent of the adjacent 1,4-DHP ring. The puckering parameters (Cremer & Pople, 1975) are Q = 0.447 (4) Å, q₂ = 0.321 (4) Å, q₃ = 0.311 (4) Å, θ = 45.9 (5)° and ϕ₂ = 110.9 (7)° for the atom sequence C5—C6—C7—C8—C8a—C4a, indicating that the envelope is distorted towards a half-chair conformation (Boeyens, 1987). Atoms C6 and C7 lie 0.134 (6) and -0.521 (8) Å, respectively, from the plane defined by atoms C4a, C5, C8 and C8a. The r.m.s. deviation of these latter four atoms from their mean plane is 0.023 Å and the maximum deviation is 0.030 (2) Å for atom C4a. In the minor conformation, the envelope flap, C7A, flips to the opposite side of the oxocyclohexene ring plane. The puckering parameters are Q = 0.423 (9) Å, q₂ = 0.377 (6) Å, q₃ = -0.192 (6) Å, θ = 117.0 (9)° and ϕ₂ = 307.5 (9)°, indicating that the envelope is distorted towards a screw-boat conformation. Atom C7A lies 0.664 (14) Å from the plane defined by atoms C4a, C5, C8 and C8a. It has been noted previously (Şimşek et al., 2000) that C7 is always the out-of-plane atom in structures involving the 5-oxoquinoline or 1,8-dioxoacridine moieties. Of the 51 hits (27 structures) for these moieties in the current release of the CSD, 43 have C7 on the same side of the ring plane as the substituent at C4 of the 1,4-DHP ring, so the major conformation of (I) belongs to the less common class in this respect.

Most of the bond lengths and angles in (I) have normal values. The C2═C3 bond is slightly shorter than the C4a═C8a bond, and the bond lengths about N1 are slightly asymmetric (Table 1). This may be an indication that N1 conjugates more strongly with the C4a═C8a bond than with the C2═C3 bond. An intermolecular hydrogen bond between the amine group and the carbonyl O atom of the oxocyclohexene ring of a neighbouring molecule (Table 2) links the molecules into infinite one-dimensional chains, which spiral parallel to the z axis and have a graph-set motif of C(6) (Bernstein et al., 1995).

S2. Experimental

The title compound was synthesized by refluxing 4,4-dimethyl-1,3-cyclohexanedione (0.01 mol), N,N-diethylacetoacetamide (0.01 mol), 3-nitrobenzaldehyde (0.01 mol) and ammonium acetate (0.03 mol) in methanol for 8 h. The solution was then poured into water and the precipitate which formed was filtered, dried and recrystallized from 2-propanol (m.p. 465 K).

S3. Refinement

The oxocyclohexene ring is disordered over two envelope conformations, with the methylene group at C7 occupying two positions, and, as a consequence, the dimethyl substituents at C6 are also disordered. The site occupation factors of the disordered atoms were refined, while constraining their sum for the two conformations to 1.0. The major conformation was found to be present in 69.8 (6)% of the molecules. Mild bond length restraints were applied to all bonds involving the disordered atoms so as to maintain reasonable geometry. The position of the amine H atom was determined from a difference Fourier map and refined freely along with its isotropic displacement parameter. The methyl H atoms were constrained to an ideal geometry (C—H = 0.98 Å) with U_iso(H) = 1.5U_eq(C), but were allowed to rotate freely about the C—C bonds. All remaining H atoms were placed in geometrically idealized positions (C—H = 0.95–1.00 Å) and constrained to ride on their parent atoms, with U_iso(H) = 1.2U_eq(C). The space group symmetry dictates that the compound is racemic, yet the structure possesses a polar axis. Due to the absence of any significant anomalous scatterers in the compound, attempts to confirm the absolute structure by refinement of the Flack parameter (Flack, 1983) in the presence of 1792 sets of Friedel equivalents led to an inconclusive value (Flack & Bernardinelli, 2000) of -0.6 (12) for this parameter. Therefore, the absolute direction of the polar axis was assigned arbitrarily. Friedel opposites were not merged before the final refinement, because the nature of the asymmetric unit in space group R3c means that doing so leads to a severe paucity of unique reflections and, for this structure, the subsequent refinement of the structure was less stable.

Computing details

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, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2002).

Figures

Fig. 1. The molecular structure of (I) showing the major conformation of the disordered oxocyclohexene ring, 50% probability displacement ellipsoids and the atom-labelling scheme. H atoms are drawn as small spheres of arbitrary radii.

N,N-Diethyl-2,6,6-trimethyl-4-(3-nitrophenyl)-5-oxo- 1,4,5,6,7,8-hexahydroquinoline-3-carboxamide

Crystal data

C23H29N3O4	Dx = 1.251 Mg m^−3
Mr = 411.50	Melting point: 465 K
Trigonal, R3c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: R 3 -2"c	Cell parameters from 3851 reflections
a = 28.2157 (11) Å	θ = 2.0–25.0°
c = 14.2592 (4) Å	µ = 0.09 mm^−1
V = 9831.2 (6) Å^3	T = 160 K
Z = 18	Needle, yellow
F(000) = 3960	0.25 × 0.05 × 0.02 mm

Data collection

Nonius KappaCCD area-detector diffractometer	2571 reflections with I > 2σ(I)
Radiation source: Nonius FR591 sealed tube generator	Rint = 0.106
Horizontally mounted graphite crystal monochromator	θmax = 25.0°, θmin = 3.0°
Detector resolution: 9 pixels mm^-1	h = 0→33
ϕ and ω scans with κ offsets	k = −28→0
27763 measured reflections	l = −16→16
3733 independent reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: geom & difmap
R[F^2 > 2σ(F^2)] = 0.047	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.090	w = 1/[σ^2(Fo^2) + (0.0233P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 1.00	(Δ/σ)max = 0.001
3730 reflections	Δρmax = 0.15 e Å^−3
311 parameters	Δρmin = −0.15 e Å^−3
9 restraints	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.00120 (9)

Special details

Experimental. Solvent used: 2-propanol Cooling Device: Oxford Cryosystems Cryostream 700 Crystal mount: glued on a glass fibre Mosaicity (°.): 0.665 (2) Frames collected: 355 Seconds exposure per frame: 105 Degrees rotation per frame: 0.7 Crystal-Detector distance (mm): 30.0

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.

Least-squares planes (x,y,z in crystal coordinates) and deviations from them (* indicates atom used to define plane)

27.9847 (0.0072) x - 15.6704 (0.0288) y + 1.5353 (0.0284) z = 10.1306 (0.0093)

* 0.0092 (0.0016) C2 * -0.0088 (0.0015) C3 * 0.0086 (0.0015) C4a * -0.0090 (0.0015) C8a -0.0217 (0.0042) N1 0.0136 (0.0045) C4

Rms deviation of fitted atoms = 0.0089

28.0122 (0.0041) x - 15.6397 (0.0281) y + 1.4189 (0.0158) z = 10.1555 (0.0076)

* -0.0088 (0.0021) N1 * 0.0164 (0.0020) C2 * -0.0129 (0.0021) C3 * 0.0023 (0.0020) C4 * 0.0046 (0.0021) C4a * -0.0016 (0.0022) C8a

Rms deviation of fitted atoms = 0.0095

28.1048 (0.0043) x - 15.7148 (0.0384) y + 0.8092 (0.0202) z = 10.2272 (0.0135)

* 0.0444 (0.0021) C4a * -0.0578 (0.0023) C5 * 0.0353 (0.0017) C6 * -0.0152 (0.0017) C8 * -0.0068 (0.0023) C8a -0.6063 (0.0060) C7 0.5787 (0.0130) C7A

Rms deviation of fitted atoms = 0.0370

28.0167 (0.0081) x - 16.7052 (0.0593) y + 0.6178 (0.0213) z = 9.9125 (0.0209)

* 0.0296 (0.0020) C4a * -0.0140 (0.0010) C5 * 0.0137 (0.0009) C8 * -0.0293 (0.0020) C8a 0.1337 (0.0064) C6 - 0.5214 (0.0075) C7 0.6637 (0.0135) C7A

Rms deviation of fitted atoms = 0.0230

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 (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
O1	0.39182 (10)	0.12500 (9)	0.36799 (13)	0.0492 (6)
O2	0.31176 (10)	0.11720 (9)	0.37212 (14)	0.0573 (7)
O5	0.52825 (8)	0.29057 (8)	0.15964 (12)	0.0449 (6)
O10	0.44533 (9)	0.08392 (9)	0.05824 (13)	0.0459 (6)
N1	0.49518 (11)	0.22467 (11)	−0.14841 (17)	0.0407 (7)
H1	0.5071 (11)	0.2353 (12)	−0.2031 (19)	0.035 (9)*
N10	0.37025 (11)	0.06389 (10)	−0.02845 (14)	0.0382 (6)
N17	0.35587 (13)	0.13147 (10)	0.33329 (16)	0.0430 (7)
C2	0.46402 (12)	0.16970 (13)	−0.12135 (18)	0.0364 (8)
C3	0.45100 (12)	0.15644 (13)	−0.03114 (18)	0.0328 (8)
C4	0.47126 (12)	0.19882 (12)	0.04667 (17)	0.0316 (7)
H4	0.4953	0.1916	0.0887	0.038*
C4a	0.50540 (12)	0.25631 (12)	0.00793 (19)	0.0339 (7)
C5	0.53184 (12)	0.30048 (13)	0.0740 (2)	0.0377 (8)
C6	0.56246 (13)	0.35941 (13)	0.03981 (18)	0.0481 (9)
C7	0.58920 (18)	0.3616 (2)	−0.0541 (2)	0.0494 (16)	0.698 (6)
H71	0.6066	0.3993	−0.0790	0.059*	0.698 (6)
H72	0.6183	0.3522	−0.0445	0.059*	0.698 (6)
C7A	0.5500 (6)	0.3665 (4)	−0.0611 (4)	0.069 (5)	0.302 (6)
H73	0.5783	0.4030	−0.0838	0.083*	0.302 (6)
H74	0.5142	0.3650	−0.0637	0.083*	0.302 (6)
C8	0.54838 (14)	0.32250 (13)	−0.1258 (2)	0.0503 (9)
H81	0.5236	0.3360	−0.1452	0.060*	0.698 (6)
H82	0.5683	0.3213	−0.1821	0.060*	0.698 (6)
H83	0.5326	0.3241	−0.1870	0.060*	0.302 (6)
H84	0.5862	0.3303	−0.1371	0.060*	0.302 (6)
C8a	0.51525 (12)	0.26584 (13)	−0.0859 (2)	0.0371 (8)
C9	0.44877 (14)	0.12999 (13)	−0.20158 (19)	0.0463 (9)
H91	0.4269	0.0925	−0.1780	0.069*
H92	0.4821	0.1344	−0.2312	0.069*
H93	0.4274	0.1372	−0.2478	0.069*
C10	0.42151 (14)	0.09881 (13)	0.00244 (19)	0.0355 (8)
C11	0.34440 (14)	0.00573 (13)	−0.00454 (18)	0.0440 (9)
H111	0.3117	−0.0045	0.0346	0.053*
H112	0.3703	−0.0005	0.0331	0.053*
C12	0.32747 (14)	−0.03080 (13)	−0.09018 (19)	0.0495 (10)
H121	0.2992	−0.0274	−0.1246	0.074*
H122	0.3129	−0.0689	−0.0706	0.074*
H123	0.3593	−0.0197	−0.1308	0.074*
C13	0.33546 (12)	0.08142 (14)	−0.07716 (19)	0.0431 (8)
H131	0.3235	0.0618	−0.1378	0.052*
H132	0.3576	0.1210	−0.0910	0.052*
C14	0.28549 (14)	0.07115 (16)	−0.0222 (2)	0.0601 (10)
H141	0.2620	0.0317	−0.0116	0.090*
H142	0.2651	0.0850	−0.0575	0.090*
H143	0.2968	0.0900	0.0384	0.090*
C15	0.42290 (12)	0.19233 (11)	0.10524 (18)	0.0298 (7)
C16	0.41144 (12)	0.16625 (11)	0.19167 (18)	0.0328 (7)
H16	0.4347	0.1541	0.2166	0.039*
C17	0.36610 (12)	0.15820 (11)	0.24086 (18)	0.0322 (8)
C18	0.33033 (13)	0.17409 (13)	0.20814 (19)	0.0385 (8)
H18	0.2992	0.1678	0.2436	0.046*
C19	0.34139 (14)	0.19966 (12)	0.1215 (2)	0.0410 (8)
H19	0.3174	0.2109	0.0964	0.049*
C20	0.38712 (13)	0.20885 (12)	0.07136 (17)	0.0356 (8)
H20	0.3943	0.2268	0.0124	0.043*
C21	0.5185 (2)	0.3758 (2)	0.0286 (4)	0.068 (2)	0.698 (6)
H211	0.5352	0.4130	0.0030	0.102*	0.698 (6)
H212	0.5022	0.3747	0.0898	0.102*	0.698 (6)
H213	0.4900	0.3503	−0.0143	0.102*	0.698 (6)
C22	0.6036 (3)	0.3968 (2)	0.1112 (3)	0.076 (2)	0.698 (6)
H221	0.6336	0.3889	0.1157	0.115*	0.698 (6)
H222	0.5857	0.3910	0.1725	0.115*	0.698 (6)
H223	0.6182	0.4350	0.0920	0.115*	0.698 (6)
C21a	0.6223 (3)	0.3730 (5)	0.0428 (11)	0.089 (6)	0.302 (6)
H214	0.6271	0.3479	0.0017	0.134*	0.302 (6)
H215	0.6321	0.3693	0.1072	0.134*	0.302 (6)
H216	0.6461	0.4107	0.0214	0.134*	0.302 (6)
C22a	0.5608 (7)	0.4006 (4)	0.1067 (8)	0.067 (5)	0.302 (6)
H224	0.5829	0.4376	0.0811	0.100*	0.302 (6)
H225	0.5755	0.3984	0.1678	0.100*	0.302 (6)
H226	0.5229	0.3923	0.1142	0.100*	0.302 (6)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0673 (18)	0.0547 (17)	0.0361 (12)	0.0383 (15)	0.0039 (11)	0.0058 (10)
O2	0.0564 (17)	0.0600 (17)	0.0471 (14)	0.0228 (14)	0.0202 (12)	0.0087 (12)
O5	0.0458 (15)	0.0444 (15)	0.0358 (12)	0.0160 (12)	0.0035 (10)	−0.0041 (10)
O10	0.0560 (17)	0.0438 (15)	0.0444 (12)	0.0298 (13)	−0.0090 (11)	0.0000 (10)
N1	0.0455 (19)	0.042 (2)	0.0262 (15)	0.0154 (15)	0.0058 (13)	0.0032 (14)
N10	0.0385 (18)	0.0351 (17)	0.0399 (15)	0.0177 (15)	−0.0050 (12)	0.0012 (12)
N17	0.056 (2)	0.0382 (18)	0.0341 (16)	0.0232 (17)	0.0081 (15)	−0.0002 (13)
C2	0.035 (2)	0.038 (2)	0.0366 (17)	0.0188 (18)	0.0001 (14)	−0.0018 (15)
C3	0.0330 (19)	0.038 (2)	0.0308 (16)	0.0201 (17)	0.0021 (13)	0.0011 (14)
C4	0.0315 (19)	0.036 (2)	0.0285 (14)	0.0176 (16)	0.0019 (13)	0.0008 (13)
C4a	0.0303 (19)	0.039 (2)	0.0330 (17)	0.0174 (16)	0.0004 (13)	−0.0004 (14)
C5	0.0300 (19)	0.040 (2)	0.0375 (18)	0.0130 (17)	0.0039 (14)	0.0023 (15)
C6	0.044 (2)	0.035 (2)	0.049 (2)	0.0076 (19)	0.0045 (16)	−0.0015 (16)
C7	0.038 (4)	0.045 (3)	0.044 (3)	0.005 (3)	0.003 (2)	0.007 (2)
C7A	0.075 (11)	0.034 (8)	0.064 (9)	0.002 (8)	0.002 (8)	0.007 (6)
C8	0.056 (2)	0.041 (2)	0.0381 (17)	0.013 (2)	0.0102 (16)	0.0082 (16)
C8a	0.036 (2)	0.036 (2)	0.0357 (18)	0.0148 (17)	−0.0010 (14)	0.0012 (16)
C9	0.055 (2)	0.048 (2)	0.0325 (16)	0.0226 (19)	0.0032 (15)	−0.0046 (15)
C10	0.043 (2)	0.038 (2)	0.0281 (16)	0.0228 (19)	0.0035 (15)	−0.0018 (15)
C11	0.051 (2)	0.038 (2)	0.0377 (16)	0.0191 (18)	0.0039 (15)	0.0031 (15)
C12	0.052 (2)	0.046 (2)	0.0451 (19)	0.020 (2)	0.0012 (16)	−0.0043 (16)
C13	0.043 (2)	0.044 (2)	0.0410 (18)	0.0210 (19)	−0.0021 (16)	0.0025 (15)
C14	0.046 (2)	0.052 (3)	0.081 (3)	0.024 (2)	0.0098 (19)	0.012 (2)
C15	0.0323 (19)	0.0241 (18)	0.0309 (16)	0.0126 (15)	−0.0038 (13)	−0.0041 (12)
C16	0.039 (2)	0.0318 (19)	0.0317 (17)	0.0206 (17)	0.0019 (14)	−0.0001 (13)
C17	0.036 (2)	0.0240 (18)	0.0293 (16)	0.0098 (16)	0.0031 (14)	−0.0018 (12)
C18	0.037 (2)	0.039 (2)	0.0378 (18)	0.0174 (17)	0.0061 (14)	−0.0054 (14)
C19	0.044 (2)	0.042 (2)	0.0423 (18)	0.0262 (18)	−0.0043 (15)	−0.0048 (15)
C20	0.037 (2)	0.036 (2)	0.0285 (16)	0.0142 (17)	0.0027 (14)	0.0028 (13)
C21	0.091 (5)	0.042 (4)	0.073 (4)	0.035 (4)	0.028 (4)	0.013 (3)
C22	0.062 (5)	0.062 (4)	0.058 (4)	−0.005 (4)	0.007 (3)	−0.010 (3)
C21a	0.080 (12)	0.036 (9)	0.109 (13)	−0.003 (8)	−0.021 (9)	0.006 (8)
C22a	0.054 (11)	0.039 (8)	0.074 (9)	0.000 (8)	0.021 (8)	−0.001 (7)

Geometric parameters (Å, º)

O1—N17	1.221 (3)	C9—H91	0.9800
O2—N17	1.232 (3)	C9—H92	0.9800
O5—C5	1.246 (3)	C9—H93	0.9800
O10—C10	1.242 (3)	C11—C12	1.513 (4)
N1—C2	1.401 (4)	C11—H111	0.9900
N1—C8a	1.345 (4)	C11—H112	0.9900
N1—H1	0.84 (3)	C12—H121	0.9800
N10—C10	1.353 (4)	C12—H122	0.9800
N10—C11	1.464 (4)	C12—H123	0.9800
N10—C13	1.475 (4)	C13—C14	1.509 (4)
N17—C17	1.474 (3)	C13—H131	0.9900
C2—C3	1.339 (4)	C13—H132	0.9900
C2—C9	1.506 (4)	C14—H141	0.9800
C3—C10	1.487 (4)	C14—H142	0.9800
C3—C4	1.518 (4)	C14—H143	0.9800
C4—C4a	1.517 (4)	C15—C16	1.388 (4)
C4—C15	1.531 (4)	C15—C20	1.393 (4)
C4—H4	1.0000	C16—C17	1.375 (4)
C4a—C8a	1.365 (4)	C16—H16	0.9500
C4a—C5	1.438 (4)	C17—C18	1.375 (4)
C5—C6	1.520 (4)	C18—C19	1.385 (4)
C6—C7	1.523 (4)	C18—H18	0.9500
C6—C7A	1.518 (5)	C19—C20	1.382 (4)
C6—C21	1.535 (4)	C19—H19	0.9500
C6—C22	1.508 (4)	C20—H20	0.9500
C6—C21a	1.534 (12)	C21—H211	0.9800
C6—C22a	1.522 (5)	C21—H212	0.9800
C7—C8	1.522 (4)	C21—H213	0.9800
C7—H71	0.9900	C22—H221	0.9800
C7—H72	0.9900	C22—H222	0.9800
C7A—C8	1.529 (5)	C22—H223	0.9800
C7A—H73	0.9900	C21a—H214	0.9800
C7A—H74	0.9900	C21a—H215	0.9800
C8—C8a	1.503 (4)	C21a—H216	0.9800
C8—H81	0.9900	C22a—H224	0.9800
C8—H82	0.9900	C22a—H225	0.9800
C8—H83	0.9900	C22a—H226	0.9800
C8—H84	0.9900
C2—N1—C8a	122.3 (2)	H91—C9—H92	109.5
C8a—N1—H1	113 (2)	C2—C9—H93	109.5
C2—N1—H1	125 (2)	H91—C9—H93	109.5
C10—N10—C11	119.5 (2)	H92—C9—H93	109.5
C10—N10—C13	123.9 (3)	O10—C10—N10	121.6 (3)
C11—N10—C13	116.3 (2)	O10—C10—C3	118.3 (3)
O1—N17—O2	123.2 (3)	N10—C10—C3	120.1 (3)
O1—N17—C17	118.3 (3)	N10—C11—C12	112.7 (2)
O2—N17—C17	118.5 (3)	N10—C11—H111	109.0
N1—C2—C3	120.4 (3)	C12—C11—H111	109.0
C3—C2—C9	125.9 (3)	N10—C11—H112	109.0
N1—C2—C9	113.7 (2)	C12—C11—H112	109.0
C2—C3—C10	122.7 (3)	H111—C11—H112	107.8
C2—C3—C4	122.7 (3)	C11—C12—H121	109.5
C10—C3—C4	114.2 (2)	C11—C12—H122	109.5
C3—C4—C4a	111.3 (2)	H121—C12—H122	109.5
C3—C4—C15	110.0 (2)	C11—C12—H123	109.5
C4a—C4—C15	112.2 (2)	H121—C12—H123	109.5
C3—C4—H4	107.7	H122—C12—H123	109.5
C4a—C4—H4	107.7	N10—C13—C14	113.9 (2)
C15—C4—H4	107.7	N10—C13—H131	108.8
C8a—C4a—C5	120.3 (3)	C14—C13—H131	108.8
C4—C4a—C8a	121.7 (3)	N10—C13—H132	108.8
C5—C4a—C4	117.7 (2)	C14—C13—H132	108.8
O5—C5—C4a	119.9 (3)	H131—C13—H132	107.7
O5—C5—C6	119.9 (3)	C13—C14—H141	109.5
C4a—C5—C6	120.2 (2)	C13—C14—H142	109.5
C22—C6—C5	111.5 (3)	H141—C14—H142	109.5
C7A—C6—C5	113.9 (5)	C13—C14—H143	109.5
C7A—C6—C22a	113.3 (6)	H141—C14—H143	109.5
C5—C6—C22a	114.6 (5)	H142—C14—H143	109.5
C22—C6—C7	111.9 (4)	C16—C15—C20	118.0 (3)
C5—C6—C7	108.9 (3)	C16—C15—C4	120.3 (3)
C7A—C6—C21a	107.0 (8)	C20—C15—C4	121.5 (2)
C5—C6—C21a	102.6 (5)	C17—C16—C15	119.4 (3)
C22a—C6—C21a	104.0 (9)	C17—C16—H16	120.3
C22—C6—C21	108.3 (4)	C15—C16—H16	120.3
C5—C6—C21	105.1 (3)	C16—C17—C18	123.2 (3)
C7—C6—C21	110.8 (3)	C16—C17—N17	118.0 (3)
C8—C7—C6	112.4 (3)	C18—C17—N17	118.9 (3)
C8—C7—H71	109.1	C17—C18—C19	117.5 (3)
C6—C7—H71	109.1	C17—C18—H18	121.3
C8—C7—H72	109.1	C19—C18—H18	121.3
C6—C7—H72	109.1	C20—C19—C18	120.4 (3)
H71—C7—H72	107.9	C20—C19—H19	119.8
C6—C7A—C8	112.3 (4)	C18—C19—H19	119.8
C6—C7A—H73	109.1	C19—C20—C15	121.5 (3)
C8—C7A—H73	109.1	C19—C20—H20	119.2
C6—C7A—H74	109.1	C15—C20—H20	119.2
C8—C7A—H74	109.1	C6—C21—H211	109.5
H73—C7A—H74	107.9	C6—C21—H212	109.5
C8a—C8—C7	111.0 (3)	C6—C21—H213	109.5
C8a—C8—C7A	112.6 (5)	C6—C22—H221	109.5
C8a—C8—H81	109.4	C6—C22—H222	109.5
C7—C8—H81	109.4	C6—C22—H223	109.5
C8a—C8—H82	109.4	C6—C21a—H214	109.5
C7—C8—H82	109.4	C6—C21a—H215	109.5
H81—C8—H82	108.0	H214—C21a—H215	109.5
C8a—C8—H83	109.1	C6—C21a—H216	109.5
C7A—C8—H83	109.1	H214—C21a—H216	109.5
C8a—C8—H84	109.1	H215—C21a—H216	109.5
C7A—C8—H84	109.1	C6—C22a—H224	109.5
H83—C8—H84	107.8	C6—C22a—H225	109.5
N1—C8a—C4a	121.6 (3)	H224—C22a—H225	109.5
N1—C8a—C8	115.9 (2)	C6—C22a—H226	109.5
C4a—C8a—C8	122.6 (3)	H224—C22a—H226	109.5
C2—C9—H91	109.5	H225—C22a—H226	109.5
C2—C9—H92	109.5
C8a—N1—C2—C3	3.1 (4)	C2—N1—C8a—C8	179.4 (3)
C8a—N1—C2—C9	−176.1 (3)	C5—C4a—C8a—N1	173.7 (3)
N1—C2—C3—C10	−175.5 (3)	C4—C4a—C8a—N1	−0.1 (5)
C9—C2—C3—C10	3.6 (5)	C5—C4a—C8a—C8	−7.0 (5)
N1—C2—C3—C4	−3.4 (4)	C4—C4a—C8a—C8	179.2 (3)
C9—C2—C3—C4	175.7 (3)	C7—C8—C8a—N1	−153.9 (3)
C2—C3—C4—C4a	2.0 (4)	C7A—C8—C8a—N1	156.6 (5)
C10—C3—C4—C4a	174.7 (3)	C7—C8—C8a—C4a	26.8 (5)
C2—C3—C4—C15	127.0 (3)	C7A—C8—C8a—C4a	−22.7 (7)
C10—C3—C4—C15	−60.3 (3)	C11—N10—C10—O10	−7.2 (4)
C3—C4—C4a—C8a	−0.2 (4)	C13—N10—C10—O10	165.9 (3)
C15—C4—C4a—C8a	−124.0 (3)	C11—N10—C10—C3	172.2 (2)
C3—C4—C4a—C5	−174.2 (2)	C13—N10—C10—C3	−14.7 (4)
C15—C4—C4a—C5	62.0 (3)	C2—C3—C10—O10	116.8 (3)
C8a—C4a—C5—O5	−170.8 (3)	C4—C3—C10—O10	−55.8 (4)
C4—C4a—C5—O5	3.2 (4)	C2—C3—C10—N10	−62.5 (4)
C8a—C4a—C5—C6	11.4 (5)	C4—C3—C10—N10	124.8 (3)
C4—C4a—C5—C6	−174.6 (3)	C10—N10—C11—C12	−122.1 (3)
O5—C5—C6—C22	23.5 (5)	C13—N10—C11—C12	64.3 (3)
C4a—C5—C6—C22	−158.7 (4)	C10—N10—C13—C14	−113.3 (3)
O5—C5—C6—C7A	−163.2 (6)	C11—N10—C13—C14	60.0 (3)
C4a—C5—C6—C7A	14.6 (6)	C3—C4—C15—C16	101.5 (3)
O5—C5—C6—C22a	−30.4 (8)	C4a—C4—C15—C16	−133.9 (3)
C4a—C5—C6—C22a	147.4 (8)	C3—C4—C15—C20	−74.1 (3)
O5—C5—C6—C7	147.5 (3)	C4a—C4—C15—C20	50.4 (4)
C4a—C5—C6—C7	−34.6 (4)	C20—C15—C16—C17	−0.7 (4)
O5—C5—C6—C21a	81.6 (7)	C4—C15—C16—C17	−176.5 (2)
C4a—C5—C6—C21a	−100.6 (7)	C15—C16—C17—C18	1.0 (4)
O5—C5—C6—C21	−93.7 (3)	C15—C16—C17—N17	−178.7 (2)
C4a—C5—C6—C21	84.1 (4)	O1—N17—C17—C16	10.6 (4)
C22—C6—C7—C8	178.0 (5)	O2—N17—C17—C16	−170.1 (3)
C5—C6—C7—C8	54.2 (5)	O1—N17—C17—C18	−169.1 (3)
C21—C6—C7—C8	−60.9 (5)	O2—N17—C17—C18	10.2 (4)
C5—C6—C7A—C8	−43.0 (11)	C16—C17—C18—C19	−0.4 (4)
C22a—C6—C7A—C8	−176.4 (9)	N17—C17—C18—C19	179.3 (2)
C21a—C6—C7A—C8	69.6 (11)	C17—C18—C19—C20	−0.5 (4)
C6—C7—C8—C8a	−50.9 (5)	C18—C19—C20—C15	0.8 (5)
C6—C7A—C8—C8a	46.9 (11)	C16—C15—C20—C19	−0.2 (4)
C2—N1—C8a—C4a	−1.3 (5)	C4—C15—C20—C19	175.6 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O5^i	0.84 (3)	2.04 (3)	2.856 (3)	163 (3)

Symmetry code: (i) x, x−y, z−1/2.