Polymorphic forms of cilostazol

Two unique conformational polymorphic forms of the compound 6-[4-(1-cyclo­hexyl-1H-tetrazol-5-yl)­butoxy]-3,4-di­hydro­quinolin-2(1H)-one (cilostazol), C₂₀H₂₇N₅O₂, have been discovered and characterized using single-crystal X-ray structural analysis. A third polymorph also exists, but acceptable crystals could not be obtained. Features of both reported polymorphic structures include a chair conformation of the cyclo­hexyl ring and puckering in the quinolinone ring. The major feature distinguishing the two polymorphic forms is a rotational twisting of the butoxy chain between the tetrazole and quinolinone rings. This difference in conformation influences the intermolecular forces, and hence the packing of the two mol­ecules during crystallization.

S1. Comment

6-[4-(1-Cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydroquinolin-2(1H)-one (cilostazol), (I), belongs to a class of compounds with proven activity as antithrombotic agents. Recently, two additional thermally produced crystalline polymorphic forms of this material were discovered, (IB) and (IC) (Stowell & Whittle, 2002; Stowell et al., 2002). Due to the poor solubility of the currently marketed active pharmaceutical ingredient, (IA), new polymorphs are of significant interest to the pharmaceutical industry, as they may have enhanced solubility, bioavailabilty, stability and other desirable characteristics. This paper presents the single-crystal analysis of (IA) and (IC). Suitable crystals of (IB) could not be isolated. To our knowledge, these are the first reported crystal structure determinations of (IA) and/or (IC). \sch

The present X-ray data allowed for the determination of the molecular conformation and packing for cilostazol, (IA) (Fig. 1). The structural data for (IC) (Fig. 2) showed distinct differences in the molecular conformation and packing diagrams compared with (IA). The bond lengths and angles for (IA) and (IC) are in accordance with anticipated values.

In (IA), the puckering parameters (Cremer & Pople, 1975) for the six-membered cyclohexyl ring (C21/C22/C23/C24/C25/C26) are q₂ = 0.010 (2) Å, ϕ₂ = 93.0 (95)° and θ = 1.0 (2)°. The latter value is close to zero, indicating a chair conformation of the ring. Puckering parameters for the quinolinone ring (N1/C2/C3/C4/C5/C10) are q₂ = 0.395 (2) Å, ϕ₂ = 146.2 (2)° and θ = 59.1 (2)°. The values for ϕ₂ and θ indicate a skew boat conformation for this ring.

In (IC), the puckering parameters for the six-membered cyclohexyl ring (C21/C22/C23/C24/C25/C26) are q₃ = 0.556 (2) Å, ϕ₂ = 10.9 (46)° and θ = 1.4 (2)°. This matches the parameters for (IA), indicating that the rings in (IA) and (IC) share the same molecular conformation. The puckering parameters for the quinolinone ring (N1/C2/C3/C4/C5/C10) are q₂ = 0.407 (2) Å, ϕ₂ = 322.1 (2)° and θ = 64.2 (3)°. The values for ϕ₂ and θ indicate a skew boat conformation for this ring, matching the conformation for (IA).

A comparison of the additional structural features of these two polymorphs reveals significant differences between them. A comparison of the torsion angles shows a twisting of the molecules, from atom O11 extending through to the cyclohexyl ring (Tables 1 and 2); additional geometric details are available in the archived CIFs. The O11—C12—C13—C14, C12—C13—C14—C15 and C14—C15—C16—N20 torsion angles demonstrate the most significant differences between the two polymorphs. Figs. 3 and 4 illustrate the unit-cell packing and show the differences between the packing of the two polymorphs.

S2. Experimental

Cilostazol, form (IA), was isolated without recrystallization from bulk active pharmaceutical ingredient received from Laboratorios Phoenix, Buenos Aires, Argentina (Lot 1002974001). A colourless needle-like crystal of (I) was isolated from this lot and was found to crystallize in the orthorhombic space group Pbca. Cilostazol, form (IC), was isolated from material recovered after performing heat-cycling experiments using differential scanning calorimetry (Stowell & Whittle, 2002; Stowell et al., 2002). The material used for heat cycling was obtained from Laboratorios Phoenix, Buenos Aires, Argentina (Lot 1002974001). A single colourless plate-like crystal isolated from the resulting heat-cycled material was found to crystallize in the monoclinic space group P2₁/n.

S3. Refinement

For (IA), atoms C3 and C4 were disordered with a site-occupancy factor of 0.80, while atoms C3A and C4A had a site-occupancy factor of 0.20. Atoms C3A and C4A were located in difference Fourier maps; however, all parameters were fixed in the final cycles of refinement. H atoms on C3A and C4A were calculated and fixed, with C—H = 1.00 Å and U_iso(H) = 1.3U_eq(C). All other H atoms in both polymorphs were initially located in a difference Fourier map, but were calculated and fixed in the final cycles of refinement to an ideal geometry, with C—H = 1.00 Å and U_iso(H) = 1.3U_eq(C), and N—H = 0.95 Å and U_iso(H) = 1.3U_eq(N).

Computing details

For both compounds, data collection: KappaCCD Server Software (Nonius, 1997); cell refinement: KappaCCD Server Software; data reduction: DENZO and SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SIR (Burla et al., 1989); program(s) used to refine structure: LSFM in OpenMolEN (Nonius, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: CIFGEN in OpenMolEN.

Figures

	Fig. 1. A molecular view of (IA), showing 30% probability displacement ellipsoids. H atoms are drawn as small spheres of arbitrary radii. For clarity, atoms C3A and C4A of the minor conformation of the 3,4-dihydroquinolin-2(1H)-one ring are not shown.
	Fig. 2. A molecular view of (IC) showing 30% probability displacement ellipsoids. H atoms are drawn as small spheres of arbitrary radii.
	Fig. 3. A drawing of the unit cell of (IA), viewed along a. Is this added text OK?
	Fig. 4. A drawing of the unit cell of (IC), viewed along a. Is this added text OK?

(IA) 6-[4-(1-Cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydroquinolin-2(1H)-one

Crystal data

C20H27N5O2	Dx = 1.26 Mg m^−3
Mr = 369.47	Melting point: 432 K
Orthorhombic, Pbca	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 3849 reflections
a = 11.324 (1) Å	θ = 1.1–25.4°
b = 9.855 (1) Å	µ = 0.08 mm^−1
c = 35.012 (1) Å	T = 294 K
V = 3907.3 (5) Å^3	Needle, colourless
Z = 8	0.58 × 0.08 × 0.05 mm
F(000) = 1584

Data collection

95mm CCD camera on κ goniostat diffractometer	2341 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.028
Horizontally mounted graphite crystal monochromator	θmax = 25.4°, θmin = 2.5°
Detector resolution: 9 pixels mm^-1	h = 0→13
CCD scans	k = 0→11
4045 measured reflections	l = −42→0
3548 independent reflections

Refinement

Refinement on F	0 constraints
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.042	w = 4Fo^2/[σ^2(Fo^2) + 0.0001Fo^4]
wR(F^2) = 0.042	(Δ/σ)max = 0.001
S = 2.10	Δρmax = 0.13 e Å^−3
2540 reflections	Δρmin = −0.15 e Å^−3
255 parameters	Extinction correction: isotropic (Zachariasen, 1963), eq. 22, p. 292 in Larson, A. C. (1970). Crystallographic Computing, edited by F. R. Ahmed, S. R. Hall & C. P. Huber, pp. 291-294. Copenhagen: Munksgaard.
132 restraints	Extinction coefficient: 1.2770 × 10^-06

Special details

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 distance, 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) treatmemt of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Orthonormal Equation of Plane 1

-0.7333 X + 0.6324 Y + -0.2495 Z - -5.7886 = 0

0.0004 0.0005 0.0006 0.0056

Crystallographic Equation of Plane

-8.3040 X + 6.2330 Y + -8.7360 Z - -5.7886 = 0

0.0049 0.0050 0.0216 0.0056

Atom X Y Z Distance Esd

C16 7.1994 2.4774 8.3155 0.0011 ± 0.0013 N17 6.3003 1.5783 8.6892 - 0.0014 ± 0.0012 N18 6.0267 0.8313 7.5897 0.0011 ± 0.0012 N19 6.7200 1.2342 6.5794 - 0.0004 ± 0.0011 N20 7.4667 2.2746 7.0223 - 0.0005 ± 0.0010 Chi Squared = 3.4

Orthonormal Equation of Plane 2

0.1931 X + 0.7871 Y + -0.5858 Z - -1.7175 = 0

0.0010 0.0004 0.0007 0.0206

Crystallographic Equation of Plane

2.1870 X + 7.7571 Y + -20.5105 Z - -1.7175 = 0

0.0116 0.0042 0.0254 0.0206

Atom X Y Z Distance Esd

C2 7.5768 9.1880 17.8120 - 0.0219 ± 0.0016 C5 8.8217 7.4913 15.8714 0.0198 ± 0.0013 C10 7.4533 7.7414 15.8607 - 0.0413 ± 0.0013 N1 6.9094 8.6685 16.7826 0.0433 ± 0.0011 Chi Squared = 2992.3

Orthonormal Equation of Plane 3

0.1422 X + 0.7574 Y + -0.6373 Z - -3.1903 = 0

0.0006 0.0004 0.0004 0.0101

Crystallographic Equation of Plane

1.6105 X + 7.4640 Y + -22.3137 Z - -3.1903 = 0

0.0065 0.0036 0.0149 0.0101

Atom X Y Z Distance Esd

C5 8.8217 7.4913 15.8714 0.0034 ± 0.0013 C6 9.3359 6.6001 14.9501 - 0.0112 ± 0.0014 C7 8.5265 5.9861 14.0055 0.0106 ± 0.0013 C8 7.1667 6.2280 14.0097 - 0.0022 ± 0.0014 C9 6.6414 7.1088 14.9444 - 0.0056 ± 0.0014 C10 7.4533 7.7414 15.8607 0.0050 ± 0.0013 Chi Squared = 170.4

Orthonormal Equation of Plane 4

0.7906 X + 0.0479 Y + -0.6104 Z - 0.7349 = 0

0.0006 0.0022 0.0007 0.0108

Crystallographic Equation of Plane

8.9531 X + 0.4719 Y + -21.3715 Z - 0.7349 = 0

0.0068 0.0218 0.0250 0.0108

Atom X Y Z Distance Esd

C16 7.1994 2.4774 8.3155 0.0000 ± 0.0014 C15 7.8305 3.4754 9.2113 0.0000 ± 0.0016 C14 8.6833 2.8146 10.2641 0.0000 ± 0.0016

Orthonormal Equation of Plane 5

0.7893 X + 0.0428 Y + -0.6125 Z - 0.6872 = 0

0.0006 0.0024 0.0007 0.0126

Crystallographic Equation of Plane

8.9379 X + 0.4217 Y + -21.4453 Z - 0.6872 = 0

0.0066 0.0236 0.0245 0.0126

Atom X Y Z Distance Esd

C15 7.8305 3.4754 9.2113 0.0000 ± 0.0016 C14 8.6833 2.8146 10.2641 0.0000 ± 0.0016 C13 9.3757 3.7680 11.2229 0.0000 ± 0.0016

Orthonormal Equation of Plane 6

-0.1314 X + 0.7488 Y + -0.6497 Z - -5.7018 = 0

0.0021 0.0007 0.0006 0.0222

Crystallographic Equation of Plane

-1.4878 X + 7.3793 Y + -22.7464 Z - -5.7018 = 0

0.0243 0.0064 0.0215 0.0222

Atom X Y Z Distance Esd

C14 8.6833 2.8146 10.2641 0.0000 ± 0.0015 C13 9.3757 3.7680 11.2229 0.0000 ± 0.0015 C12 8.4180 4.4256 12.1745 0.0000 ± 0.0014

Orthonormal Equation of Plane 7

-0.0612 X + 0.7912 Y + -0.6084 Z - -4.4211 = 0

0.0018 0.0004 0.0006 0.0182

Crystallographic Equation of Plane

-0.6934 X + 7.7979 Y + -21.3022 Z - -4.4211 = 0

0.0209 0.0044 0.0205 0.0182

Atom X Y Z Distance Esd

C13 9.3757 3.7680 11.2229 0.0000 ± 0.0015 C12 8.4180 4.4256 12.1745 0.0000 ± 0.0013 O11 9.1882 5.1952 13.0978 0.0000 ± 0.0009

Orthonormal Equation of Plane 8

0.0184 X + 0.7604 Y + -0.6492 Z - -4.3831 = 0

0.0019 0.0005 0.0006 0.0189

Crystallographic Equation of Plane

0.2082 X + 7.4942 Y + -22.7285 Z - -4.3831 = 0

0.0212 0.0050 0.0208 0.0189

Atom X Y Z Distance Esd

C12 8.4180 4.4256 12.1745 0.0000 ± 0.0013 O11 9.1882 5.1952 13.0978 0.0000 ± 0.0010 C7 8.5265 5.9861 14.0055 0.0000 ± 0.0013

Dihedral Angles Between Planes: ——————————- Plane No. Plane No. Dihedral Angle ——— ——— ————– 1 2 59.85 ± 0.07 1 3 57.74 ± 0.05 1 4 113.40 ± 0.10 1 5 113.51 ± 0.10 1 6 42.95 ± 0.15 1 7 45.80 ± 0.12 1 8 50.99 ± 0.11 2 3 4.49 ± 0.51 2 4 56.77 ± 0.14 2 5 56.98 ± 0.15 2 6 19.17 ± 0.17 2 7 14.67 ± 0.19 2 8 10.77 ± 0.26 3 4 57.47 ± 0.12 3 5 57.65 ± 0.13 3 6 15.75 ± 0.17 3 7 11.95 ± 0.19 3 8 7.13 ± 0.33 4 5 0.33 ± 4.31 4 6 70.82 ± 0.15 4 7 68.85 ± 0.14 4 8 63.44 ± 0.15 5 6 70.96 ± 0.15 5 7 69.01 ± 0.15 5 8 63.60 ± 0.15 6 7 5.26 ± 0.54 6 8 8.62 ± 0.33 7 8 5.42 ± 0.46

Refinement. Refinement of F against all reflections. The weighted R-factor wR and goodness of fit S are based on F, conventional R-factors R are based on F, with F set to zero or negative F².

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
O2	0.62329 (9)	1.0167 (1)	0.53035 (4)	0.0916 (7)
O11	0.81141 (7)	0.52716 (9)	0.37410 (3)	0.0619 (6)
N1	0.6102 (1)	0.8796 (1)	0.47935 (4)	0.0577 (7)
N17	0.5564 (1)	0.1602 (1)	0.24818 (4)	0.0714 (8)
N18	0.5322 (1)	0.0844 (1)	0.21678 (4)	0.0715 (8)
N19	0.5934 (1)	0.1252 (1)	0.18792 (4)	0.0647 (7)
N20	0.65938 (9)	0.23081 (9)	0.20057 (3)	0.0493 (6)
C2	0.6691 (1)	0.9323 (2)	0.50875 (5)	0.0689 (9)
C3	0.7882 (2)	0.8711 (2)	0.51669 (6)	0.065 (1)	0.800
C4	0.8548 (2)	0.8434 (2)	0.47936 (6)	0.057 (1)	0.800
C5	0.7790 (1)	0.7601 (1)	0.45332 (4)	0.0506 (8)
C6	0.8245 (1)	0.6697 (1)	0.42701 (4)	0.0532 (8)
C7	0.7530 (1)	0.6074 (1)	0.40002 (4)	0.0503 (8)
C8	0.6329 (1)	0.6319 (1)	0.40015 (4)	0.0557 (8)
C9	0.5865 (1)	0.7213 (1)	0.42684 (5)	0.0563 (8)
C10	0.6582 (1)	0.7855 (1)	0.45302 (4)	0.0497 (8)
C12	0.7434 (1)	0.4491 (1)	0.34773 (4)	0.0543 (8)
C13	0.8280 (1)	0.3823 (1)	0.32055 (5)	0.0625 (9)
C14	0.7668 (1)	0.2856 (1)	0.29316 (5)	0.0655 (9)
C15	0.6915 (1)	0.3526 (1)	0.26309 (5)	0.0605 (9)
C16	0.6358 (1)	0.2514 (1)	0.23751 (4)	0.0525 (8)
C21	0.7463 (1)	0.2946 (1)	0.17484 (4)	0.0493 (8)
C22	0.8558 (1)	0.2070 (1)	0.17191 (5)	0.0567 (8)
C23	0.9458 (1)	0.2710 (1)	0.14548 (5)	0.065 (1)
C24	0.8936 (1)	0.3009 (1)	0.10667 (5)	0.072 (1)
C25	0.7839 (1)	0.3889 (1)	0.11007 (5)	0.069 (1)
C26	0.6929 (1)	0.3238 (1)	0.13606 (5)	0.0593 (9)
C3A	0.8115	0.9432	0.5000	0.0577	0.200
C4A	0.8475	0.8030	0.4916	0.0449	0.200
H1	0.5305	0.9070	0.4758	0.0753*
H3a	0.7775	0.7837	0.5308	0.0865*	0.800
H3b	0.8353	0.9353	0.5327	0.0865*	0.800
H4a	0.9294	0.7930	0.4851	0.0750*	0.800
H4b	0.8744	0.9315	0.4667	0.0750*	0.800
H6	0.9108	0.6487	0.4274	0.0696*
H8	0.5801	0.5860	0.3813	0.0726*
H9	0.4996	0.7394	0.4271	0.0739*
H12a	0.6882	0.5096	0.3334	0.0706*
H12b	0.6970	0.3785	0.3617	0.0706*
H13a	0.8877	0.3303	0.3357	0.0814*
H13b	0.8687	0.4544	0.3054	0.0814*
H14a	0.7151	0.2239	0.3085	0.0854*
H14b	0.8290	0.2310	0.2799	0.0854*
H15a	0.7422	0.4145	0.2475	0.0799*
H15b	0.6282	0.4066	0.2760	0.0799*
H21	0.7702	0.3840	0.1859	0.0642*
H22a	0.8332	0.1158	0.1617	0.0744*
H22b	0.8913	0.1963	0.1979	0.0744*
H23a	1.0138	0.2073	0.1423	0.0860*
H23b	0.9742	0.3577	0.1571	0.0860*
H24a	0.8720	0.2135	0.0940	0.0939*
H24b	0.9537	0.3495	0.0908	0.0939*
H25a	0.7487	0.4015	0.0841	0.0912*
H25b	0.8067	0.4792	0.1208	0.0912*
H26a	0.6244	0.3868	0.1392	0.0771*
H26b	0.6652	0.2369	0.1244	0.0771*
H3Aa	0.8547	0.9789	0.5228	0.0756*	0.200
H3Ab	0.8267	1.0035	0.4776	0.0756*	0.200
H4Aa	0.8248	0.7417	0.5132	0.0612*	0.200
H4Ab	0.9348	0.7983	0.4876	0.0612*	0.200

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O2	0.0778 (7)	0.1194 (7)	0.0828 (8)	0.0330 (6)	−0.0203 (7)	−0.0503 (7)
O11	0.0545 (5)	0.0722 (5)	0.0604 (7)	−0.0049 (5)	0.0039 (6)	−0.0181 (5)
N1	0.0517 (6)	0.0644 (6)	0.0577 (8)	0.0068 (6)	−0.0049 (6)	−0.0103 (6)
N17	0.0683 (8)	0.0733 (7)	0.073 (1)	−0.0095 (6)	0.0178 (7)	−0.0015 (7)
N18	0.0607 (7)	0.0710 (7)	0.085 (1)	−0.0152 (6)	0.0123 (7)	−0.0077 (7)
N19	0.0592 (7)	0.0631 (6)	0.073 (1)	−0.0180 (6)	0.0046 (7)	−0.0137 (7)
N20	0.0460 (6)	0.0473 (5)	0.0551 (8)	−0.0074 (5)	0.0014 (6)	−0.0083 (6)
C2	0.0646 (9)	0.0846 (9)	0.060 (1)	0.0153 (8)	−0.0120 (9)	−0.0186 (9)
C3	0.063 (1)	0.084 (1)	0.053 (1)	0.015 (1)	−0.010 (1)	−0.016 (1)
C4	0.055 (1)	0.070 (1)	0.049 (1)	−0.0014 (9)	−0.003 (1)	−0.002 (1)
C5	0.0475 (8)	0.0570 (7)	0.0479 (9)	−0.0016 (6)	−0.0027 (7)	−0.0013 (7)
C6	0.0465 (8)	0.0612 (7)	0.053 (1)	−0.0012 (7)	−0.0005 (7)	−0.0015 (8)
C7	0.0524 (8)	0.0509 (6)	0.0478 (9)	−0.0037 (7)	0.0034 (7)	−0.0004 (7)
C8	0.0527 (8)	0.0609 (7)	0.054 (1)	−0.0059 (7)	−0.0036 (8)	−0.0052 (8)
C9	0.0467 (7)	0.0665 (8)	0.057 (1)	−0.0007 (7)	−0.0038 (7)	−0.0043 (8)
C10	0.0521 (7)	0.0499 (7)	0.0471 (9)	0.0015 (6)	−0.0004 (7)	−0.0000 (7)
C12	0.0570 (8)	0.0522 (7)	0.054 (1)	−0.0066 (7)	−0.0021 (8)	−0.0060 (7)
C13	0.0605 (9)	0.0662 (8)	0.061 (1)	0.0043 (7)	−0.0013 (8)	−0.0092 (8)
C14	0.0700 (9)	0.0594 (8)	0.068 (1)	0.0130 (7)	−0.0044 (9)	−0.0144 (8)
C15	0.077 (1)	0.0557 (7)	0.052 (1)	0.0025 (7)	0.0012 (9)	−0.0059 (8)
C16	0.0530 (8)	0.0512 (6)	0.053 (1)	0.0029 (6)	0.0045 (8)	−0.0032 (7)
C21	0.0491 (7)	0.0470 (7)	0.0521 (9)	−0.0074 (6)	0.0015 (7)	−0.0056 (7)
C22	0.0474 (7)	0.0674 (8)	0.057 (1)	0.0006 (7)	−0.0066 (8)	0.0018 (8)
C23	0.0514 (8)	0.0773 (9)	0.070 (1)	−0.0020 (8)	0.0075 (8)	−0.0056 (9)
C24	0.077 (1)	0.0784 (9)	0.061 (1)	−0.0002 (9)	0.0131 (9)	−0.0018 (9)
C25	0.083 (1)	0.0681 (8)	0.059 (1)	0.0008 (8)	0.0018 (9)	0.0064 (9)
C26	0.0595 (8)	0.0566 (7)	0.062 (1)	0.0058 (7)	−0.0051 (8)	0.0015 (8)
C3A	0.0543	0.068 (4)	0.052 (5)	0.004 (3)	−0.008 (4)	0.008 (4)
C4A	0.0480	0.063 (4)	0.030 (4)	−0.013 (3)	−0.007 (3)	0.016 (3)

Geometric parameters (Å, º)

O2—C2	1.238 (2)	C12—H12b	1.000
O11—C7	1.374 (2)	C13—C14	1.519 (2)
O11—C12	1.428 (2)	C13—H13a	1.000
N1—C2	1.332 (2)	C13—H13b	1.000
N1—C10	1.416 (2)	C14—C15	1.507 (2)
N1—H1	0.950	C14—H14a	1.000
N17—N18	1.357 (2)	C14—H14b	1.000
N17—C16	1.325 (2)	C15—C16	1.482 (2)
N18—N19	1.290 (2)	C15—H15a	1.000
N19—N20	1.355 (2)	C15—H15b	1.000
N20—C16	1.336 (2)	C21—C22	1.514 (2)
N20—C21	1.475 (2)	C21—C26	1.514 (2)
C2—C3	1.503 (3)	C21—H21	1.000
C2—C3A	1.645	C22—C23	1.514 (2)
C3—C4	1.533 (4)	C22—H22a	1.000
C3—H3a	1.000	C22—H22b	1.000
C3—H3b	1.000	C23—C24	1.511 (3)
C4—C5	1.497 (3)	C23—H23a	1.000
C4—H4a	1.000	C23—H23b	1.000
C4—H4b	1.000	C24—C25	1.519 (2)
C5—C6	1.381 (2)	C24—H24a	1.000
C5—C10	1.391 (2)	C24—H24b	1.000
C5—C4A	1.606	C25—C26	1.517 (2)
C6—C7	1.387 (2)	C25—H25a	1.000
C6—H6	1.000	C25—H25b	1.000
C7—C8	1.381 (2)	C26—H26a	1.000
C8—C9	1.388 (2)	C26—H26b	1.000
C8—H8	1.000	C3A—C4A	1.4702
C9—C10	1.378 (2)	C3A—H3Aa	1.0000
C9—H9	1.000	C3A—H3Ab	1.0000
C12—C13	1.502 (2)	C4A—H4Aa	1.0000
C12—H12a	1.000	C4A—H4Ab	1.0000
C7—O11—C12	118.5 (1)	C15—C14—H14b	108.1
C2—N1—C10	124.5 (1)	H14a—C14—H14b	109.5
C2—N1—H1	117.8	C14—C15—C16	111.6 (1)
C10—N1—H1	117.8	C14—C15—H15a	108.9
N18—N17—C16	106.4 (1)	C14—C15—H15b	108.9
N17—N18—N19	110.7 (1)	C16—C15—H15a	108.9
N18—N19—N20	106.3 (1)	C16—C15—H15b	108.9
N19—N20—C16	108.8 (1)	H15a—C15—H15b	109.5
N19—N20—C21	119.7 (1)	N17—C16—N20	107.8 (1)
C16—N20—C21	131.3 (1)	N17—C16—C15	125.1 (2)
N1—C2—C3	115.8 (2)	N20—C16—C15	127.0 (1)
N1—C2—C3A	111.9	N20—C21—C22	110.2 (1)
C2—C3—C4	110.8 (2)	N20—C21—C26	111.3 (1)
C2—C3—H3a	109.1	N20—C21—H21	108.7
C2—C3—H3b	109.1	C22—C21—C26	112.0 (1)
C4—C3—H3a	109.1	C22—C21—H21	107.9
C4—C3—H3b	109.1	C26—C21—H21	106.7
H3a—C3—H3b	109.5	C21—C22—C23	110.8 (1)
C3—C4—C5	109.5 (2)	C21—C22—H22a	109.1
C3—C4—H4a	109.5	C21—C22—H22b	109.1
C3—C4—H4b	109.5	C23—C22—H22a	109.1
C5—C4—H4a	109.5	C23—C22—H22b	109.1
C5—C4—H4b	109.5	H22a—C22—H22b	109.5
H4a—C4—H4b	109.5	C22—C23—C24	111.6 (1)
C4—C5—C6	123.1 (2)	C22—C23—H23a	108.9
C4—C5—C10	118.0 (2)	C22—C23—H23b	108.9
C6—C5—C10	118.5 (1)	C24—C23—H23a	108.9
C6—C5—C4A	123.2	C24—C23—H23b	108.9
C10—C5—C4A	115.7	H23a—C23—H23b	109.5
C5—C6—C7	121.5 (1)	C23—C24—C25	111.1 (2)
C5—C6—H6	119.2	C23—C24—H24a	109.1
C7—C6—H6	119.2	C23—C24—H24b	109.0
O11—C7—C6	115.1 (1)	C25—C24—H24a	109.1
O11—C7—C8	125.2 (1)	C25—C24—H24b	109.1
C6—C7—C8	119.7 (1)	H24a—C24—H24b	109.5
C7—C8—C9	119.1 (1)	C24—C25—C26	111.2 (1)
C7—C8—H8	120.5	C24—C25—H25a	109.1
C9—C8—H8	120.5	C24—C25—H25b	109.1
C8—C9—C10	121.1 (1)	C26—C25—H25a	109.0
C8—C9—H9	119.5	C26—C25—H25b	109.0
C10—C9—H9	119.5	H25a—C25—H25b	109.5
N1—C10—C5	119.4 (1)	C21—C26—C25	110.3 (1)
N1—C10—C9	120.5 (1)	C21—C26—H26a	109.3
C5—C10—C9	120.1 (1)	C21—C26—H26b	109.3
O11—C12—C13	107.6 (1)	C25—C26—H26a	109.3
O11—C12—H12a	109.9	C25—C26—H26b	109.3
O11—C12—H12b	109.9	H26a—C26—H26b	109.5
C13—C12—H12a	109.9	C2—C3A—C4A	104.33
C13—C12—H12b	109.9	C2—C3A—H3Aa	110.74
H12a—C12—H12b	109.5	C2—C3A—H3Ab	110.74
C12—C13—C14	112.6 (1)	C4A—C3A—H3Aa	110.74
C12—C13—H13a	108.7	C4A—C3A—H3Ab	110.74
C12—C13—H13b	108.7	H3Aa—C3A—H3Ab	109.47
C14—C13—H13a	108.7	C5—C4A—C3A	106.25
C14—C13—H13b	108.7	C5—C4A—H4Aa	110.27
H13a—C13—H13b	109.5	C5—C4A—H4Ab	110.27
C13—C14—C15	115.1 (1)	C3A—C4A—H4Aa	110.27
C13—C14—H14a	108.1	C3A—C4A—H4Ab	110.27
C13—C14—H14b	108.1	H4Aa—C4A—H4Ab	109.47
C15—C14—H14a	108.1
C12—O11—C7—C6	174.0 (1)	C4A—C5—C6—C7	162.6
C12—O11—C7—C8	−8.0 (2)	C4—C5—C10—N1	−5.4 (2)
C7—O11—C12—C13	174.6 (1)	C4—C5—C10—C9	173.4 (1)
C10—N1—C2—O2	178.3 (1)	C6—C5—C10—N1	−179.0 (1)
C10—N1—C2—C3	−8.7 (2)	C6—C5—C10—C9	−0.1 (2)
C10—N1—C2—C3A	29.5 (2)	C4A—C5—C10—N1	18.7
C2—N1—C10—C5	−10.6 (2)	C4A—C5—C10—C9	−162.4
C2—N1—C10—C9	170.5 (1)	C6—C5—C4A—C3A	149.1
C16—N17—N18—N19	0.3 (2)	C10—C5—C4A—C3A	−49.5
N18—N17—C16—N20	−0.3 (1)	C5—C6—C7—O11	175.8 (1)
N18—N17—C16—C15	−177.5 (1)	C5—C6—C7—C8	−2.4 (2)
N17—N18—N19—N20	−0.2 (1)	O11—C7—C8—C9	−176.5 (1)
N18—N19—N20—C21	175.6 (1)	C6—C7—C8—C9	1.5 (2)
N19—N20—C16—N17	0.2 (2)	C7—C8—C9—C10	0.1 (2)
N19—N20—C16—C15	177.3 (1)	C8—C9—C10—N1	178.1 (1)
C21—N20—C16—N17	−174.8 (1)	C8—C9—C10—C5	−0.8 (2)
C21—N20—C16—C15	2.4 (2)	O11—C12—C13—C14	174.7 (1)
N19—N20—C21—C22	−77.3 (1)	C12—C13—C14—C15	71.0 (2)
N19—N20—C21—C26	47.5 (1)	C13—C14—C15—C16	179.7 (1)
C16—N20—C21—C22	97.2 (1)	C14—C15—C16—N17	64.9 (2)
C16—N20—C21—C26	−138.0 (1)	C14—C15—C16—N20	−111.7 (2)
O2—C2—C3—C4	−146.2 (2)	N20—C21—C22—C23	179.9 (1)
N1—C2—C3—C4	40.9 (2)	C26—C21—C22—C23	55.5 (1)
O2—C2—C3A—C4A	152.0	N20—C21—C26—C25	−179.8 (1)
N1—C2—C3A—C4A	−58.2	C22—C21—C26—C25	−56.1 (1)
C2—C3—C4—C5	−53.4 (2)	C21—C22—C23—C24	−54.8 (2)
C3—C4—C5—C6	−150.0 (1)	C22—C23—C24—C25	55.4 (2)
C3—C4—C5—C10	36.8 (2)	C23—C24—C25—C26	−56.0 (2)
C4—C5—C6—C7	−171.5 (1)	C24—C25—C26—C21	55.9 (2)
C10—C5—C6—C7	1.7 (2)	C2—C3A—C4A—C5	64.24

(IC) 6-[4-(1-Cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydroquinolin-2(1H)-one

Crystal data

C20H27N5O2	F(000) = 792
Mr = 369.47	Dx = 1.26 Mg m^−3
Monoclinic, P21/n	Melting point: 419 K
Hall symbol: -P 2yn	Mo Kα radiation, λ = 0.71073 Å
a = 5.148 (1) Å	Cell parameters from 3878 reflections
b = 10.739 (1) Å	θ = 1.4–27.5°
c = 35.279 (1) Å	µ = 0.08 mm^−1
β = 94.070 (1)°	T = 294 K
V = 1945.3 (6) Å^3	Plate, colourless
Z = 4	0.22 × 0.12 × 0.06 mm

Data collection

95mm CCD camera on κ-goniometer diffractometer	2223 reflections with I > 2σ(I)
Radiation source: fine-focued sealed tube	Rint = 0.026
Horizontally mounted graphite crystal monochromator	θmax = 27.5°, θmin = 2.5°
Detector resolution: 9 pixels mm^-1	h = 0→6
CCD scans	k = 0→13
4572 measured reflections	l = −45→45
4343 independent reflections

Refinement

Refinement on F	0 constraints
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.043	w = 4Fo^2/[σ^2(Fo^2) + 0.0004Fo^4]
wR(F^2) = 0.041	(Δ/σ)max = 0.001
S = 4.19	Δρmax = 0.13 e Å^−3
2223 reflections	Δρmin = −0.12 e Å^−3
245 parameters	Extinction correction: isotropic (Zachariasen, 1963), eq. 22, p. 292 in Larson, A. C. (1970). Crystallographic Computing, edited by F. R. Ahmed, S. R. Hall & C. P. Huber, pp. 291-294. Copenhagen: Munksgaard.
108 restraints	Extinction coefficient: 3.7536 × 10^-06

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedran 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 distance, 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) treatmemt of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Orthonormal Equation of Plane 1

0.6844 X + -0.6239 Y + -0.3772 Z - -15.0972 = 0

0.0006 0.0006 0.0007 0.0181

Crystallographic Equation of Plane

3.5231 X + -6.7005 Y + -14.9871 Z - -15.0972 = 0

0.0031 0.0067 0.0666 0.0181

Atom X Y Z Distance Esd

C16 - 2.6850 5.3759 26.2505 0.0039 ± 0.0016 N17 - 1.9986 6.4168 25.7961 - 0.0044 ± 0.0014 N18 - 1.1299 6.7605 26.7833 0.0034 ± 0.0015 N19 - 1.2749 5.9843 27.8154 - 0.0010 ± 0.0014 N20 - 2.2604 5.1020 27.4892 - 0.0018 ± 0.0013 Chi Squared = 23.4

Orthonormal Equation of Plane 2

-0.7705 X + -0.0216 Y + -0.6371 Z - -13.6084 = 0

0.0006 0.0012 0.0007 0.0109

Crystallographic Equation of Plane

-3.9662 X + -0.2318 Y + -20.4892 Z - -13.6084 = 0

0.0030 0.0128 0.0661 0.0109

Atom X Y Z Distance Esd

C2 3.3818 1.9396 17.1523 0.0335 ± 0.0017 C5 1.8065 3.3243 19.1112 - 0.0307 ± 0.0015 C10 1.8062 1.9366 19.0104 0.0638 ± 0.0015 N1 2.7206 1.3025 18.1306 - 0.0666 ± 0.0013 Chi Squared = 4990.1

Orthonormal Equation of Plane 3

-0.7035 X + 0.0625 Y + -0.7079 Z - -14.5985 = 0

0.0005 0.0007 0.0005 0.0089

Crystallographic Equation of Plane

-3.6213 X + 0.6711 Y + -23.1505 Z - -14.5985 = 0

0.0024 0.0070 0.0558 0.0089

Atom X Y Z Distance Esd

C5 1.8065 3.3243 19.1112 0.0057 ± 0.0015 C6 0.9519 3.9202 20.0156 0.0039 ± 0.0015 C7 0.1041 3.1580 20.8102 - 0.0098 ± 0.0015 C8 0.0900 1.7852 20.6804 0.0061 ± 0.0016 C9 0.9507 1.1810 19.7755 0.0036 ± 0.0016 C10 1.8062 1.9366 19.0104 - 0.0095 ± 0.0015 Chi Squared = 119.0

Orthonormal Equation of Plane 4

0.0343 X + 0.6813 Y + -0.7312 Z - -15.6251 = 0

0.0024 0.0007 0.0006 0.0225

Crystallographic Equation of Plane

0.1765 X + 7.3161 Y + -25.8179 Z - -15.6251 = 0

0.0123 0.0077 0.1243 0.0225

Atom X Y Z Distance Esd

C16 - 2.6850 5.3759 26.2505 0.0000 ± 0.0016 C15 - 3.6839 4.5971 25.4781 0.0000 ± 0.0017 C14 - 3.0329 3.5671 24.5489 0.0000 ± 0.0016

Orthonormal Equation of Plane 5

-0.8023 X + 0.0306 Y + -0.5961 Z - -12.0916 = 0

0.0006 0.0023 0.0008 0.0199

Crystallographic Equation of Plane

-4.1300 X + 0.3285 Y + -18.9680 Z - -12.0916 = 0

0.0031 0.0247 0.0672 0.0199

Atom X Y Z Distance Esd

C15 - 3.6839 4.5971 25.4781 0.0000 ± 0.0016 C14 - 3.0329 3.5671 24.5489 0.0000 ± 0.0016 C13 - 2.1950 4.1826 23.4528 0.0000 ± 0.0016

Orthonormal Equation of Plane 6

-0.7965 X + 0.0075 Y + -0.6046 Z - -12.4010 = 0

0.0006 0.0024 0.0008 0.0185

Crystallographic Equation of Plane

-4.0999 X + 0.0801 Y + -19.2824 Z - -12.4010 = 0

0.0030 0.0255 0.0661 0.0185

Atom X Y Z Distance Esd

C14 - 3.0329 3.5671 24.5489 0.0000 ± 0.0016 C13 - 2.1950 4.1826 23.4528 0.0000 ± 0.0016 C12 - 1.5358 3.1617 22.5719 0.0000 ± 0.0016

Orthonormal Equation of Plane 7

-0.7542 X + 0.0758 Y + -0.6522 Z - -13.3241 = 0

0.0006 0.0022 0.0006 0.0169

Crystallographic Equation of Plane

-3.8824 X + 0.8142 Y + -21.0632 Z - -13.3241 = 0

0.0029 0.0232 0.0633 0.0169

Atom X Y Z Distance Esd

C13 - 2.1950 4.1826 23.4528 0.0000 ± 0.0016 C12 - 1.5358 3.1617 22.5719 0.0000 ± 0.0016 O11 - 0.6876 3.8790 21.6744 0.0000 ± 0.0011

Orthonormal Equation of Plane 8

-0.7319 X + 0.0130 Y + -0.6813 Z - -14.2132 = 0

0.0006 0.0021 0.0007 0.0170

Crystallographic Equation of Plane

-3.7674 X + 0.1399 Y + -22.1422 Z - -14.2132 = 0

0.0033 0.0231 0.0674 0.0170

Atom X Y Z Distance Esd

C12 - 1.5358 3.1617 22.5719 0.0000 ± 0.0016 O11 - 0.6876 3.8790 21.6744 0.0000 ± 0.0011 C7 0.1041 3.1580 20.8102 0.0000 ± 0.0015

Dihedral Angles Between Planes: ——————————- Plane No. Plane No. Dihedral Angle ——— ——— ————– 1 2 105.88 ± 0.07 1 3 104.68 ± 0.05 1 4 97.23 ± 0.11 1 5 110.08 ± 0.10 1 6 108.77 ± 0.10 1 7 108.51 ± 0.09 1 8 104.60 ± 0.09 2 3 7.38 ± 0.36 2 4 64.87 ± 0.13 2 5 4.22 ± 0.73 2 6 2.91 ± 1.03 2 7 5.73 ± 0.51 2 8 3.91 ± 0.78 3 4 57.58 ± 0.12 3 5 8.75 ± 0.32 3 6 8.57 ± 0.32 3 7 4.38 ± 0.57 3 8 3.61 ± 0.73 4 5 64.58 ± 0.16 4 6 65.17 ± 0.16 4 7 59.82 ± 0.16 4 8 61.19 ± 0.16 5 6 1.45 ± 2.02 5 7 4.97 ± 0.60 5 8 6.42 ± 0.48 6 7 5.35 ± 0.55 6 8 5.76 ± 0.53 7 8 4.17 ± 0.70

Refinement. Refinement of F against all reflections. The weighted R-factor wR and goodness of fit S are based on F, conventional R-factors R are based on F, with F set to zero or negative F².

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

	x	y	z	Uiso*/Ueq
O2	1.0499 (2)	0.1281 (1)	0.46767 (3)	0.0866 (8)
O11	0.1660 (2)	0.3612 (1)	0.61593 (3)	0.0645 (7)
N1	0.7791 (3)	0.1215 (1)	0.51521 (3)	0.0578 (8)
N17	−0.0317 (3)	0.5975 (1)	0.73305 (3)	0.0632 (9)
N18	0.1507 (3)	0.6295 (1)	0.76112 (4)	0.0665 (9)
N19	0.1369 (3)	0.5572 (1)	0.79044 (4)	0.0629 (9)
N20	−0.0590 (2)	0.4751 (1)	0.78118 (3)	0.0503 (8)
C2	0.8942 (3)	0.1806 (2)	0.48742 (4)	0.061 (1)
C3	0.8149 (3)	0.3143 (2)	0.48132 (4)	0.064 (1)
C4	0.7883 (3)	0.3818 (2)	0.51839 (4)	0.054 (1)
C5	0.6152 (3)	0.3095 (1)	0.54308 (4)	0.0443 (9)
C6	0.4615 (3)	0.3650 (1)	0.56880 (4)	0.048 (1)
C7	0.3078 (3)	0.2941 (2)	0.59138 (4)	0.049 (1)
C8	0.3034 (3)	0.1662 (2)	0.58768 (4)	0.055 (1)
C9	0.4580 (3)	0.1099 (1)	0.56197 (4)	0.055 (1)
C10	0.6137 (3)	0.1804 (2)	0.54022 (4)	0.048 (1)
C12	0.0137 (3)	0.2944 (2)	0.64144 (4)	0.054 (1)
C13	−0.1022 (3)	0.3894 (2)	0.66646 (4)	0.058 (1)
C14	−0.2498 (3)	0.3322 (2)	0.69761 (4)	0.054 (1)
C15	−0.3635 (3)	0.4281 (2)	0.72403 (4)	0.054 (1)
C16	−0.1587 (3)	0.5006 (2)	0.74598 (4)	0.0487 (9)
C21	−0.1289 (3)	0.3820 (2)	0.80926 (4)	0.052 (1)
C22	0.0921 (3)	0.2927 (2)	0.81763 (5)	0.069 (1)
C23	0.0298 (4)	0.1996 (2)	0.84818 (5)	0.085 (1)
C24	−0.0437 (4)	0.2652 (2)	0.88405 (5)	0.082 (1)
C25	−0.2698 (4)	0.3524 (2)	0.87509 (5)	0.081 (1)
C26	−0.2109 (3)	0.4454 (2)	0.84474 (5)	0.069 (1)
H1	0.8104	0.0346	0.5183	0.0761*
H3a	0.6438	0.3169	0.4660	0.0846*
H3b	0.9499	0.3574	0.4671	0.0846*
H4a	0.7106	0.4659	0.5130	0.0702*
H4b	0.9643	0.3915	0.5320	0.0702*
H6	0.4608	0.4578	0.5712	0.0626*
H8	0.1899	0.1146	0.6034	0.0707*
H9	0.4562	0.0173	0.5592	0.0726*
H12a	0.1264	0.2354	0.6571	0.0704*
H12b	−0.1276	0.2469	0.6269	0.0704*
H13a	−0.2246	0.4431	0.6504	0.0753*
H13b	0.0417	0.4419	0.6784	0.0753*
H14a	−0.1283	0.2767	0.7132	0.0710*
H14b	−0.3963	0.2814	0.6856	0.0710*
H15a	−0.4708	0.3834	0.7423	0.0704*
H15b	−0.4766	0.4870	0.7083	0.0704*
H21	−0.2812	0.3325	0.7985	0.0678*
H22a	0.2514	0.3408	0.8265	0.0906*
H22b	0.1256	0.2465	0.7938	0.0906*
H23a	0.1864	0.1463	0.8544	0.1133*
H23b	−0.1190	0.1461	0.8383	0.1133*
H24a	0.1091	0.3140	0.8950	0.1118*
H24b	−0.0941	0.2017	0.9029	0.1118*
H25a	−0.3077	0.3985	0.8987	0.1119*
H25b	−0.4260	0.3024	0.8660	0.1119*
H26a	−0.3706	0.4961	0.8381	0.0899*
H26b	−0.0670	0.5013	0.8549	0.0899*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O2	0.124 (1)	0.0741 (9)	0.0710 (7)	0.0248 (8)	0.0518 (6)	0.0070 (7)
O11	0.0722 (7)	0.0555 (7)	0.0670 (7)	0.0043 (6)	0.0314 (6)	−0.0014 (6)
N1	0.083 (1)	0.0457 (8)	0.0510 (8)	0.0106 (8)	0.0246 (7)	0.0019 (7)
N17	0.072 (1)	0.0615 (9)	0.0570 (8)	−0.0094 (9)	0.0151 (7)	0.0014 (8)
N18	0.075 (1)	0.061 (1)	0.0647 (9)	−0.0139 (8)	0.0177 (7)	−0.0018 (8)
N19	0.0670 (9)	0.0612 (9)	0.0606 (9)	−0.0167 (8)	0.0102 (7)	−0.0062 (8)
N20	0.0561 (8)	0.0498 (8)	0.0456 (7)	−0.0087 (7)	0.0100 (6)	−0.0029 (7)
C2	0.082 (1)	0.060 (1)	0.0461 (9)	0.010 (1)	0.0158 (9)	0.0015 (9)
C3	0.086 (1)	0.060 (1)	0.051 (1)	0.005 (1)	0.0185 (9)	0.0065 (9)
C4	0.055 (1)	0.055 (1)	0.053 (1)	0.0011 (9)	0.0098 (8)	0.0040 (9)
C5	0.0445 (9)	0.046 (1)	0.0422 (9)	0.0026 (9)	0.0030 (8)	0.0002 (8)
C6	0.052 (1)	0.042 (1)	0.0502 (9)	0.0023 (9)	0.0058 (8)	0.0001 (8)
C7	0.049 (1)	0.052 (1)	0.0461 (9)	0.0068 (9)	0.0083 (8)	−0.0031 (8)
C8	0.058 (1)	0.050 (1)	0.056 (1)	−0.0005 (9)	0.0148 (8)	0.0026 (9)
C9	0.071 (1)	0.043 (1)	0.055 (1)	0.000 (1)	0.0158 (9)	−0.0017 (9)
C10	0.053 (1)	0.050 (1)	0.0421 (9)	0.0075 (9)	0.0065 (8)	−0.0005 (8)
C12	0.055 (1)	0.060 (1)	0.0488 (9)	0.000 (1)	0.0119 (8)	0.0016 (9)
C13	0.064 (1)	0.060 (1)	0.0511 (9)	0.001 (1)	0.0163 (9)	−0.0031 (9)
C14	0.055 (1)	0.064 (1)	0.0462 (9)	−0.007 (1)	0.0073 (8)	−0.0019 (9)
C15	0.054 (1)	0.066 (1)	0.0442 (9)	−0.002 (1)	0.0102 (8)	0.0016 (9)
C16	0.054 (1)	0.051 (1)	0.0418 (8)	0.0027 (9)	0.0142 (7)	−0.0017 (8)
C21	0.059 (1)	0.056 (1)	0.0420 (9)	−0.0143 (9)	0.0067 (8)	−0.0014 (9)
C22	0.084 (1)	0.061 (1)	0.065 (1)	0.011 (1)	0.014 (1)	0.004 (1)
C23	0.111 (2)	0.072 (1)	0.078 (1)	0.002 (1)	0.004 (1)	0.017 (1)
C24	0.088 (1)	0.112 (2)	0.057 (1)	−0.024 (1)	−0.006 (1)	0.023 (1)
C25	0.081 (1)	0.127 (2)	0.051 (1)	−0.007 (1)	0.013 (1)	0.014 (1)
C26	0.073 (1)	0.084 (1)	0.053 (1)	0.008 (1)	0.0205 (9)	−0.001 (1)

Geometric parameters (Å, º)

O2—C2	1.234 (2)	C12—H12a	1.000
O11—C7	1.375 (2)	C12—H12b	1.000
O11—C12	1.428 (2)	C13—C14	1.510 (2)
N1—C2	1.341 (2)	C13—H13a	1.000
N1—C10	1.418 (2)	C13—H13b	1.000
N1—H1	0.952	C14—C15	1.533 (2)
N17—N18	1.360 (2)	C14—H14a	1.000
N17—C16	1.326 (2)	C14—H14b	1.000
N18—N19	1.300 (2)	C15—C16	1.484 (2)
N19—N20	1.362 (2)	C15—H15a	1.000
N20—C16	1.338 (2)	C15—H15b	1.000
N20—C21	1.470 (2)	C21—C22	1.502 (5)
C2—C3	1.504 (3)	C21—C26	1.511 (2)
C3—C4	1.510 (2)	C21—H21	1.000
C3—H3a	1.000	C22—C23	1.521 (3)
C3—H3b	1.000	C22—H22a	1.000
C4—C5	1.505 (2)	C22—H22b	1.000
C4—H4a	1.000	C23—C24	1.520 (3)
C4—H4b	1.000	C23—H23a	1.000
C5—C6	1.381 (2)	C23—H23b	1.000
C5—C10	1.391 (2)	C24—C25	1.510 (3)
C6—C7	1.389 (2)	C24—H24a	1.000
C6—H6	1.000	C24—H24b	1.000
C7—C8	1.380 (3)	C25—C26	1.511 (3)
C8—C9	1.387 (2)	C25—H25a	1.000
C8—H8	1.000	C25—H25b	1.000
C9—C10	1.375 (2)	C26—H26a	1.000
C9—H9	1.000	C26—H26b	1.000
C12—C13	1.500 (2)
C7—O11—C12	118.3 (1)	H13a—C13—H13b	109.4
C2—N1—C10	124.1 (2)	C13—C14—C15	113.7 (2)
C2—N1—H1	118.0	C13—C14—H14a	108.4
C10—N1—H1	118.0	C13—C14—H14b	108.4
N18—N17—C16	106.2 (2)	C15—C14—H14a	108.4
N17—N18—N19	110.8 (2)	C15—C14—H14b	108.4
N18—N19—N20	106.1 (2)	H14a—C14—H14b	109.4
N19—N20—C16	108.6 (2)	C14—C15—C16	112.5 (1)
N19—N20—C21	119.4 (2)	C14—C15—H15a	108.7
C16—N20—C21	132.0 (2)	C14—C15—H15b	108.7
N1—C2—C3	115.3 (2)	C16—C15—H15a	108.7
C2—C3—C4	112.0 (2)	C16—C15—H15b	108.7
C2—C3—H3a	108.8	H15a—C15—H15b	109.5
C2—C3—H3b	108.8	N17—C16—N20	108.3 (2)
C4—C3—H3a	108.8	N17—C16—C15	125.6 (2)
C4—C3—H3b	108.8	N20—C16—C15	126.0 (2)
H3a—C3—H3b	109.5	N20—C21—C22	110.4 (1)
C3—C4—C5	110.3 (2)	N20—C21—C26	110.4 (2)
C3—C4—H4a	109.3	N20—C21—H21	109.2
C3—C4—H4b	109.3	C22—C21—C26	112.2 (2)
C5—C4—H4a	109.2	C22—C21—H21	107.3
C5—C4—H4b	109.3	C26—C21—H21	107.3
H4a—C4—H4b	109.5	C21—C22—C23	111.4 (2)
C4—C5—C6	123.2 (2)	C21—C22—H22a	109.0
C4—C5—C10	118.2 (2)	C21—C22—H22b	109.0
C6—C5—C10	118.5 (2)	C23—C22—H22a	109.0
C5—C6—C7	121.1 (2)	C23—C22—H22b	109.0
C5—C6—H6	119.5	H22a—C22—H22b	109.5
C7—C6—H6	119.5	C22—C23—C24	111.3 (2)
O11—C7—C6	115.0 (2)	C22—C23—H23a	109.0
O11—C7—C8	125.1 (2)	C22—C23—H23b	109.0
C6—C7—C8	119.9 (2)	C24—C23—H23a	109.0
C7—C8—C9	119.3 (2)	C24—C23—H23b	109.0
C7—C8—H8	120.3	H23a—C23—H23b	109.5
C9—C8—H8	120.4	C23—C24—C25	110.3 (2)
C8—C9—C10	120.7 (2)	C23—C24—H24a	109.3
C8—C9—H9	119.7	C23—C24—H24b	109.3
C10—C9—H9	119.7	C25—C24—H24a	109.2
N1—C10—C5	119.3 (2)	C25—C24—H24b	109.3
N1—C10—C9	120.1 (2)	H24a—C24—H24b	109.5
C5—C10—C9	120.6 (2)	C24—C25—C26	111.6 (2)
O11—C12—C13	106.8 (2)	C24—C25—H25a	109.0
O11—C12—H12a	110.2	C24—C25—H25b	108.9
O11—C12—H12b	110.1	C26—C25—H25a	108.9
C13—C12—H12a	110.1	C26—C25—H25b	108.9
C13—C12—H12b	110.1	H25a—C25—H25b	109.5
H12a—C12—H12b	109.4	C21—C26—C25	111.8 (2)
C12—C13—C14	113.1 (2)	C21—C26—H26a	108.9
C12—C13—H13a	108.6	C21—C26—H26b	108.9
C12—C13—H13b	108.6	C25—C26—H26a	108.9
C14—C13—H13a	108.6	C25—C26—H26b	108.9
C14—C13—H13b	108.6	H26a—C26—H26b	109.5
C12—O11—C7—C6	−176.9 (1)	C4—C5—C6—C7	−179.0 (1)
C12—O11—C7—C8	4.1 (2)	C10—C5—C6—C7	−0.1 (2)
C7—O11—C12—C13	175.8 (1)	C4—C5—C10—N1	1.8 (2)
C10—N1—C2—O2	175.4 (1)	C4—C5—C10—C9	−179.6 (1)
C10—N1—C2—C3	−6.2 (2)	C6—C5—C10—N1	−177.2 (1)
C2—N1—C10—C5	−16.2 (2)	C6—C5—C10—C9	1.4 (2)
C2—N1—C10—C9	165.2 (1)	C5—C6—C7—O11	179.6 (1)
C16—N17—N18—N19	−0.7 (2)	C5—C6—C7—C8	−1.4 (2)
N18—N17—C16—N20	0.8 (2)	O11—C7—C8—C9	−179.5 (1)
N18—N17—C16—C15	−175.4 (1)	C6—C7—C8—C9	1.5 (2)
N17—N18—N19—N20	0.4 (2)	C7—C8—C9—C10	−0.2 (2)
N18—N19—N20—C16	0.1 (2)	C8—C9—C10—N1	177.3 (1)
N18—N19—N20—C21	−178.2 (1)	C8—C9—C10—C5	−1.3 (2)
N19—N20—C16—N17	−0.6 (2)	O11—C12—C13—C14	−174.7 (1)
N19—N20—C16—C15	175.6 (1)	C12—C13—C14—C15	178.5 (1)
C21—N20—C16—N17	177.5 (1)	C13—C14—C15—C16	−64.5 (2)
C21—N20—C16—C15	−6.4 (3)	C14—C15—C16—N17	80.6 (2)
N19—N20—C21—C22	−65.2 (2)	C14—C15—C16—N20	−94.9 (2)
N19—N20—C21—C26	59.4 (2)	N20—C21—C22—C23	177.0 (1)
C16—N20—C21—C22	116.9 (2)	C26—C21—C22—C23	53.4 (2)
C16—N20—C21—C26	−118.5 (2)	N20—C21—C26—C25	−176.8 (1)
O2—C2—C3—C4	−141.1 (2)	C22—C21—C26—C25	−53.2 (2)
N1—C2—C3—C4	40.4 (2)	C21—C22—C23—C24	−55.3 (2)
C2—C3—C4—C5	−51.6 (2)	C22—C23—C24—C25	56.4 (2)
C3—C4—C5—C6	−149.8 (1)	C23—C24—C25—C26	−56.1 (2)
C3—C4—C5—C10	31.4 (2)	C24—C25—C26—C21	54.7 (2)