Two aza­steroidal [3,2-c]­pyrazole derivatives: 2'-(p-fluoro­phenyl)-4-azapyrazolo­[4',3':2,3]-5[alpha]-androstan-17[beta]-yl acetate and 2'-(p-fluoro­phenyl)-4-azapyrazolo­[4',3':2,3]-5[alpha]-androstan-17[beta]-ol

In both the title aza-steroids, 2'-(p-fluoro­phenyl)-4-azapyra­zolo­[4',3':2,3]-5[alpha]-androstan-17[beta]-yl acetate, C₂₇H₃₄FN₃O₂, (I), and 2'-(p-fluoro­phenyl)-4-azapyrazolo­[4',3':2,3]-5[alpha]-an­dros­tan-17[beta]-ol, C₂₅H₃₂FN₃O, (II), the tetra­hydro­pyridine ring adopts a half-chair conformation and is considerably strained as a consequence of the presence of the fused planar pyrazole ring. In both compounds, both cyclo­hexane rings have chair conformations, while the cyclo­pentane ring has an envelope conformation. All the rings of the steroid nucleus are trans fused. In (I), intermolecular N-H...O, C-H...F, C-H...O and C-H...N interactions are observed in the solid state, while intermolecular N-H...O and O-H...N hydrogen bonds are observed in (II).

S1. Comment

There has been considerable interest in the synthesis and biological study of several heterocyclic steroids as extremely potent anti-inflammatory agents (Gupta et al., 1996, and references therein). It is known that 2'-phenyl-11β,17α,21-trihydroxy-16α-methyl-4-pregneno[3,2-c]pyrazol-20-one- 21-acetate and its p-flurophenyl analogue are 60 and 100 times, respectively, more active than hydrocortisone (Hirschman et al., 1963; Hirschman et al., 1964). The importance of the [3,2-c]pyrazole function has been demonstrated by a number of investigators (Hirschman et al., 1963; Fried et al., 1963; Hannah et al., 1975). Both cortivazol and nivazol have the [3,2-c]pyrazole structural component and the 3-keto function is absent, while both have been described as potent anti-inflammatory steroids (Gupta et al., 1996, and references therein). In this paper, we report the crystal and molecular structures of the ring-A-modified steroids 2'-p-fluorophenyl-4-aza-5α-androstano[3,2-c]pyrazol-17β-yl acetate, (I) and 2'-p-fluorophenyl-4-aza-5α-androstano[3,2-c]pyrazol-17β-ol, (II). Although both (I) and (II) were found to be more active than hydrocortisone, the acetoxy derivative, (I), was found to be less active than the hydroxy derivative, (II) (Gupta et al., 1996). The crystallographic analyses have been carried out in order to study the influence of the fused pyrazole moiety on the steroid skeleton. This study extends our ongoing investigation into a series of similar ring-A– or ring-D-modified steroids.

The crystals of (I) and (II) are enantiomerically pure. However, the absence of any significant anomalous scatterers in (I) and (II) prevented the determination of the absolute configuration. The enantiomer used in the refinement of the structure of (I) was assumed to correspond to the configuration of the known chiral centers in a precursor molecule, which remained unchanged during the synthesis of (I). Since (I) was the starting material for the synthesis of (II), the enantiomer used in the refinement of the structure of (II) was assumed to correspond to unchanged chiral centres passed on from (I) during the synthesis.

Figs. 1 and 2 show the asymmetric units of (I) and (II), respectively, with the atomic numbering schemes. All rings of the steroid skeleton are trans connected. The corresponding bond lengths and angles in (I) and (II) are almost equivalent and are comparable to those found in similar ring-A-modified steroids (Lisgarten & Palmer, 1998; Lisgarten et al., 2003).

In (I), ring A of the steroid nucleus adopts a half-chair conformation, being considerably strained as a consequence of ?the presence of? the fused planar pyrazole ring E [puckering parameters (Cremer & Pople, 1975) are Q = 0.493 (2) Å, q₂ = 0.391 (2) Å, q₃ = 0.300 (2) Å, θ = 52.5 (2)° and ϕ₂ = 260.2 (3)° for the atom sequence N4—C3—C2—C1—C10—C5. Steroidal rings B and C exhibit chair conformations, as seen from the puckering parameters [ring B: Q = 0.571 (2) Å, q₂ = 0.033 (2) Å, q₃ = 0.571 (2) Å, θ = 3.4 (2)° and ϕ₂ = 276 (3)° for the atom sequence C5—C6—C7—C8—C9—C10; ring C: Q = 0.580 (2) Å, q₂ = 0.052 (2) Å, q₃ = 0.578 (2) Å, θ = 4.9 (2)° and ϕ₂ = 270 (2)° for the atom sequence C8—C9—C11—C12—C13—C14]. Similar conformations have been reported in related structures (Lisgarten & Palmer, 1998; Lisgarten et al., 2003). Five-membered ring D of the steroid skeleton has a 13β envelope conformation. The pseudo-rotation angle is 350.0 (1)° and the maximum torsion angle is 47.6 (1)° for the atom sequence C13—C14—C15—C16—C17 (Rao et al., 1981). In (II), steroidal ring A also exhibits a half-chair conformation, being strained as a consequence of ?the presence of? the fused pyrazole ring E, as in (I) [puckering parameters Q = 0.466 (2) Å, q₂ = 0.367 (2) Å, q₃ = 0.287 (2) Å, θ = 52.0 (3)° and ϕ₂ = 267.5 (3)° for the atom sequence N4—C3—C2—C1—C10—C5]. The puckering parameters of steroidal rings B and C [ring B: Q = 0.579 (2) Å, q₂ = 0.050 (2) Å, q₃ = 0.577 (2) Å, θ = 4.8 (2)° and ϕ₂ = 327 (2)° for the atom sequence C5—C6—C7—C8—C9—C10; ring C: Q = 0.581 (2) Å, q₂ = 0.031 (2) Å, q₃ = 0.580 (2) Å, θ = 3.0 (2)° and ϕ₂ = 310 (4)° for the atom sequence C8—C9—C11—C12—C13—C14] are indicative of chair conformations. Five-membered ring D of the steroid nucleus has a 13β envelope conformation, with a pseudo-rotation angle of 348.3 (1)° and a maximum torsion angle of 48.9 (1)° for the atom sequence C13—C14—C15—C16—C17. The presence of either an acetoxy or a hydroxy substituent on atom C17 does not affect the conformation of ring D in (I) and (II). In related structures (Lisgarten & Palmer, 1998; Lisgarten et al., 2003), steroidal ring D also has a half-chair conformation, even when atom C17 is disubstituted (17β-hydroxy and 17a\-methyl).

The C19—C10···C13—C18 pseudo-torsion angle, which provides a quantitative measure of the twist about the length of the molecule, is found to be 0.73 (14)° in (I) and 1.36 (16)° in (II). The dihedral angles between the plane of the fluorophenyl ring and the average molecular plane through the rings E, A, B, C and D are 28.29 (5)° in (I) and 29.05 (5)° in (II). The E/A/B/C/D ring systems of the two compounds can be superimposed on one another and exhibit a small r.m.s. deviation of the matching atoms (0.168 Å), which indicates that the change in substituent on atom C17 of ring D (from acetoxy to hydroxy) does not affect the overall conformation of the steroidal nucleii.

In (I), atom N4 forms an intermolecular N—H···O hydrogen bond with carbonyl atom O30 of an adjacent molecule. This interaction links the molecules into a chain that runs parallel to the z axis and has a graph-set motif of C(12) (Bernstein et al., 1995). Atom C15 acts as a donor for a weak intermolecular C—H···F interaction with atom F26 of an adjacent molecule. This interaction links the molecules into a chain that runs parallel to the y axis and has a graph-set motif of C(15). Atom C20 is involved in an intermolecular C—H···O interaction with carbonyl atom O30 of a different adjacent molecule. This interaction links the molecules into a continuous chain that runs parallel to the x axis and has a graph-set motif of C(13). Atom C25 acts as a donor for a weak intermolecular C—H···N interaction with atom N21 of the pyrazole moiety of a symmetry-related molecule. This weak interaction links the molecules into a chain that runs parallel to the x axis and has a graph-set motif of C(6) (Table 1). Atom C31 (via H31C) is involved in an intermolecular C—H···π interaction with pyrazole ring E of a neighbouring molecule [H31C···Cg = 2.75 Å, C31···Cg = 3.665 (2) Å and C31—H31C···Cg = 155°, where Cg is the centroid of ring E at (x − 1/2,1/2 − y,-z)].

In (II), atom N4 forms an intermolecular N—H···O hydrogen bond with hydroxy atom O17 of an adjacent molecule. This interaction links the molecules into a chain that runs parallel to the z axis and has a graph-set motif of C(10) (Bernstein et al., 1995). Hydroxy atom O17 participates in an intermolecular O—H···N hydrogen bond with atom N21 of the pyrazole moiety of a different adjacent molecule. This interaction links the molecules into a continuous chain that runs parallel to the y axis and has a graph-set motif of C(12) (Table 2). The is a short intermolecular contact between atoms H16B and H19B(1/2 − x,-y,-1/2 + z) (H···H = 2.15 Å), which is smaller than the sum of the van der Waals radii of the corresponding atoms.

S2. Experimental

To a refluxing solution of 17β-acetoxy-3-chloro-4-aza-5-androst-2-en-2-aldehyde (0.5 g, 1.32 mmol) in aldehyde free ethanol (250 ml) was added glacial acetic acid (1.5 ml) drop wise. The solution was refluxed for 10 min and then p-fluorophenylhydrazine hydrochloride (0.25 g) was added; he resulting solution was refluxed for 5 h. The solution was concentrated to about 20 ml and then poured in to ice-cold water and dried. The resulting solid, (I) (institution code DPJ-308), was crystallized from acetone (yield 0.25 g, 41.9%; m.p. 511–513 K). A mixture of (I) (0.2 g, 0.443 mmol) and potassium carbonate (0.5 g) in aqueous methanol (10%, 50 ml) was stirred at room temperature for 3 h. The resulting slurry was poured in to ice-cold water, and the precipitated product was filtered, washed and dried. The resulting solid, (II) (institution code DPJ-309), was crystallized from acetone (yield 0.125 g, 68.9%; m.p. 513–515 K).

S3. Refinement

The positions of the amine H atoms in (I) and (II) and of the hydroxy H atom in (II) were determined from a difference Fourier map and refined freely, along with their isotropic displacement parameters. For both compounds, 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 idealized positions (C—H = 0.95–1.00 Å) and were constrained ride on their parent atoms. Because of the absence of any significant anomalous scatterers in (I) and (II), attempts to confirm the absolute structure by refinement of the Flack (1983) parameter in the presence of 2940 sets of Friedel equivalents for (I) [2094 for (II)] led to an inconclusive value (Flack & Bernardinelli, 2000) of 0.1 (8) [−0.1 (9) for (II)]. Therefore, the Friedel pairs were merged before the final refinement and the absolute configuration was assigned to correspond to that of the known chiral centers in a precursor molecule, which remained unchanged during the synthesis of (I). The absolute configuration of (II) was assumed to correspond to that of the known chiral centers in (I), which remained unchanged during the synthesis of (II). Reflections 013, 020, 111, 112 and 041 in (I), and 012 in (II), were partially obscured by the beam stop and were omitted.

Computing details

For both compounds, data collection: COLLECT (Nonius, 2000). Cell refinement: DENZO–SMN (Otwinowski & Minor, 1997) for (I); DENZO-SMN (Otwinowski & Minor, 1997) for (II). Data reduction: DENZO–SMN and SCALEPACK (Otwinowski & Minor, 1997) for (I); DENZO-SMN and SCALEPACK (Otwinowski & Minor, 1997) for (II). For both compounds, program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2003).

Figures

	Fig. 1. A view of the molecule of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are represented by circles of arbitrary radii.
	Fig. 2. A view of the molecule of (II), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are represented by circles of arbitrary radii.

(I) 2'-(p-fluorophenyl)-4-aza-pyrazolo[4',3':2,3]-5α-androstan-17β-yl acetate

Crystal data

C27H34FN3O2	Dx = 1.292 Mg m^−3
Mr = 451.57	Melting point: 511 K
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 3850 reflections
a = 7.2545 (1) Å	θ = 2.0–30.0°
b = 13.5417 (2) Å	µ = 0.09 mm^−1
c = 23.6387 (4) Å	T = 160 K
V = 2322.23 (6) Å^3	Prism, colourless
Z = 4	0.25 × 0.10 × 0.08 mm
F(000) = 968

Data collection

Nonius KappaCCD diffractometer	3157 reflections with I > 2σ(I)
Radiation source: Nonius FR591 sealed tube generator	Rint = 0.062
Horizontally mounted graphite crystal monochromator	θmax = 30.0°, θmin = 2.3°
Detector resolution: 9 pixels mm^-1	h = 0→10
ϕ and ω scans with κ offsets	k = 0→19
42805 measured reflections	l = 0→33
3830 independent reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.043	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.103	w = 1/[σ^2(Fo^2) + (0.0503P)^2 + 0.2409P] where P = (Fo^2 + 2Fc^2)/3
S = 1.04	(Δ/σ)max < 0.001
3825 reflections	Δρmax = 0.23 e Å^−3
306 parameters	Δρmin = −0.20 e Å^−3
0 restraints	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0093 (19)

Special details

Experimental. Solvent used: acetone Cooling Device: Oxford Cryosystems Cryostream 700 Crystal mount: glued on a glass fibre Mosaicity (°.): 0.414 (1) Frames collected: 470 Seconds exposure per frame: 78 Degrees rotation per frame: 1.3 Crystal-Detector distance (mm): 35.50

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq
F26	1.20629 (18)	0.20271 (9)	0.45368 (4)	0.0417 (3)
O29	0.43477 (19)	0.51402 (10)	−0.13771 (5)	0.0298 (3)
O30	0.5792 (2)	0.50523 (12)	−0.22164 (5)	0.0424 (4)
N4	0.8472 (2)	0.29914 (13)	0.20522 (6)	0.0245 (3)
H4	0.869 (4)	0.352 (2)	0.2269 (10)	0.061 (8)*
N21	0.5397 (2)	0.14574 (12)	0.28683 (6)	0.0300 (4)
N22	0.7004 (2)	0.19881 (12)	0.27946 (6)	0.0265 (3)
C1	0.5065 (3)	0.24673 (14)	0.13985 (7)	0.0258 (4)
H1A	0.3738	0.2632	0.1372	0.031*
H1B	0.5331	0.1937	0.1122	0.031*
C2	0.5501 (3)	0.21126 (13)	0.19837 (7)	0.0259 (4)
C3	0.7065 (3)	0.23968 (13)	0.22659 (7)	0.0246 (4)
C5	0.8249 (2)	0.31820 (13)	0.14397 (7)	0.0216 (4)
H5	0.8640	0.2566	0.1239	0.026*
C6	0.9585 (3)	0.39882 (14)	0.12614 (7)	0.0250 (4)
H6A	1.0854	0.3793	0.1368	0.030*
H6B	0.9281	0.4606	0.1465	0.030*
C7	0.9503 (2)	0.41745 (14)	0.06217 (7)	0.0240 (4)
H7A	1.0302	0.4744	0.0527	0.029*
H7B	0.9992	0.3589	0.0421	0.029*
C8	0.7545 (2)	0.43837 (13)	0.04136 (7)	0.0213 (4)
H8	0.7113	0.5021	0.0581	0.026*
C9	0.6234 (2)	0.35487 (13)	0.06033 (7)	0.0211 (4)
H9	0.6732	0.2926	0.0435	0.025*
C10	0.6233 (2)	0.33921 (13)	0.12554 (7)	0.0216 (4)
C11	0.4276 (3)	0.36747 (14)	0.03625 (7)	0.0259 (4)
H11A	0.3532	0.3086	0.0461	0.031*
H11B	0.3690	0.4256	0.0541	0.031*
C12	0.4267 (3)	0.38095 (14)	−0.02797 (7)	0.0258 (4)
H12A	0.4699	0.3194	−0.0463	0.031*
H12B	0.2992	0.3939	−0.0409	0.031*
C13	0.5506 (2)	0.46627 (13)	−0.04553 (7)	0.0229 (4)
C14	0.7470 (2)	0.44611 (14)	−0.02323 (7)	0.0225 (4)
H14	0.7834	0.3799	−0.0382	0.027*
C15	0.8664 (3)	0.52190 (15)	−0.05438 (7)	0.0275 (4)
H15A	0.9946	0.4978	−0.0584	0.033*
H15B	0.8679	0.5858	−0.0340	0.033*
C16	0.7720 (3)	0.53264 (15)	−0.11318 (7)	0.0297 (4)
H16A	0.7445	0.6028	−0.1214	0.036*
H16B	0.8525	0.5064	−0.1435	0.036*
C17	0.5934 (3)	0.47229 (14)	−0.10900 (7)	0.0256 (4)
H17	0.6164	0.4042	−0.1238	0.031*
C18	0.4717 (3)	0.56516 (14)	−0.02502 (7)	0.0275 (4)
H18A	0.3481	0.5745	−0.0409	0.041*
H18B	0.5521	0.6191	−0.0375	0.041*
H18C	0.4645	0.5650	0.0164	0.041*
C19	0.5469 (3)	0.42890 (14)	0.15773 (7)	0.0275 (4)
H19A	0.4181	0.4398	0.1469	0.041*
H19B	0.6198	0.4876	0.1483	0.041*
H19C	0.5540	0.4166	0.1985	0.041*
C20	0.4527 (3)	0.15324 (14)	0.23769 (7)	0.0292 (4)
H20	0.3374	0.1228	0.2299	0.035*
C23	0.8318 (3)	0.19894 (14)	0.32384 (7)	0.0265 (4)
C24	1.0180 (3)	0.20602 (15)	0.31219 (8)	0.0308 (4)
H24	1.0591	0.2105	0.2741	0.037*
C25	1.1450 (3)	0.20653 (16)	0.35603 (8)	0.0340 (5)
H25	1.2732	0.2117	0.3485	0.041*
C26	1.0817 (3)	0.19946 (14)	0.41054 (8)	0.0314 (4)
C27	0.8977 (3)	0.18936 (15)	0.42349 (8)	0.0326 (5)
H27	0.8584	0.1826	0.4616	0.039*
C28	0.7711 (3)	0.18932 (14)	0.37958 (8)	0.0302 (4)
H28	0.6433	0.1828	0.3874	0.036*
C30	0.4436 (3)	0.52348 (15)	−0.19410 (7)	0.0302 (4)
C31	0.2651 (3)	0.55944 (17)	−0.21817 (9)	0.0388 (5)
H31A	0.2897	0.6097	−0.2470	0.058*
H31B	0.1899	0.5882	−0.1879	0.058*
H31C	0.1988	0.5040	−0.2354	0.058*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
F26	0.0491 (7)	0.0466 (7)	0.0292 (6)	0.0030 (6)	−0.0141 (5)	0.0047 (6)
O29	0.0276 (7)	0.0392 (7)	0.0225 (6)	0.0008 (6)	−0.0043 (5)	0.0037 (5)
O30	0.0430 (9)	0.0586 (10)	0.0256 (7)	0.0072 (8)	0.0009 (6)	0.0023 (7)
N4	0.0236 (8)	0.0307 (8)	0.0191 (7)	−0.0042 (7)	−0.0007 (6)	0.0010 (7)
N21	0.0293 (8)	0.0323 (8)	0.0286 (8)	−0.0069 (7)	0.0032 (7)	0.0036 (7)
N22	0.0257 (8)	0.0309 (8)	0.0229 (7)	−0.0028 (7)	−0.0002 (6)	0.0041 (7)
C1	0.0248 (9)	0.0296 (9)	0.0232 (8)	−0.0041 (8)	−0.0007 (7)	−0.0001 (7)
C2	0.0261 (9)	0.0286 (9)	0.0229 (8)	−0.0022 (8)	0.0002 (7)	0.0000 (7)
C3	0.0257 (9)	0.0263 (9)	0.0218 (8)	−0.0004 (8)	0.0029 (7)	0.0013 (7)
C5	0.0216 (8)	0.0260 (9)	0.0172 (7)	0.0006 (7)	−0.0001 (7)	0.0003 (7)
C6	0.0190 (9)	0.0303 (9)	0.0256 (9)	−0.0041 (8)	−0.0027 (7)	0.0013 (7)
C7	0.0208 (9)	0.0273 (9)	0.0240 (8)	−0.0007 (8)	0.0003 (7)	0.0021 (7)
C8	0.0199 (8)	0.0223 (8)	0.0216 (8)	0.0000 (7)	−0.0012 (7)	−0.0010 (7)
C9	0.0188 (8)	0.0224 (9)	0.0222 (8)	0.0012 (7)	0.0003 (7)	−0.0011 (7)
C10	0.0201 (8)	0.0240 (9)	0.0208 (8)	−0.0005 (7)	0.0019 (6)	−0.0011 (7)
C11	0.0219 (9)	0.0297 (9)	0.0260 (8)	−0.0034 (8)	−0.0012 (7)	0.0047 (8)
C12	0.0245 (9)	0.0280 (9)	0.0248 (9)	−0.0041 (8)	−0.0072 (7)	0.0009 (7)
C13	0.0222 (8)	0.0248 (9)	0.0218 (8)	−0.0001 (8)	−0.0017 (7)	0.0002 (7)
C14	0.0227 (9)	0.0238 (9)	0.0210 (8)	0.0006 (7)	0.0003 (7)	−0.0007 (7)
C15	0.0246 (9)	0.0325 (10)	0.0255 (9)	−0.0017 (8)	−0.0004 (7)	0.0036 (8)
C16	0.0296 (10)	0.0354 (11)	0.0240 (9)	−0.0019 (9)	0.0013 (8)	0.0018 (8)
C17	0.0259 (9)	0.0283 (9)	0.0225 (8)	0.0030 (8)	−0.0038 (7)	0.0011 (7)
C18	0.0289 (10)	0.0276 (9)	0.0259 (9)	0.0032 (8)	−0.0012 (8)	0.0011 (7)
C19	0.0267 (9)	0.0308 (9)	0.0251 (9)	0.0021 (8)	0.0014 (8)	−0.0035 (8)
C20	0.0289 (10)	0.0289 (9)	0.0298 (9)	−0.0038 (9)	0.0034 (8)	0.0016 (8)
C23	0.0323 (10)	0.0242 (9)	0.0232 (8)	0.0013 (8)	−0.0004 (7)	0.0014 (8)
C24	0.0328 (10)	0.0353 (11)	0.0242 (8)	0.0018 (9)	0.0006 (8)	0.0039 (8)
C25	0.0313 (11)	0.0405 (12)	0.0301 (10)	0.0036 (10)	−0.0009 (8)	0.0040 (9)
C26	0.0428 (11)	0.0276 (10)	0.0237 (9)	0.0040 (9)	−0.0085 (8)	0.0029 (8)
C27	0.0440 (12)	0.0323 (11)	0.0215 (8)	0.0022 (9)	0.0017 (8)	0.0044 (8)
C28	0.0347 (11)	0.0307 (10)	0.0252 (9)	0.0017 (9)	0.0032 (8)	0.0030 (8)
C30	0.0345 (10)	0.0315 (10)	0.0247 (9)	−0.0039 (9)	−0.0044 (8)	0.0028 (8)
C31	0.0371 (12)	0.0479 (13)	0.0315 (10)	−0.0025 (10)	−0.0102 (9)	0.0056 (10)

Geometric parameters (Å, º)

F26—C26	1.364 (2)	C12—C13	1.522 (3)
O29—C30	1.341 (2)	C12—H12A	0.9900
O29—C17	1.450 (2)	C12—H12B	0.9900
O30—C30	1.205 (2)	C13—C17	1.534 (2)
N4—C3	1.394 (2)	C13—C18	1.535 (3)
N4—C5	1.480 (2)	C13—C14	1.544 (2)
N4—H4	0.90 (3)	C14—C15	1.532 (2)
N21—C20	1.326 (2)	C14—H14	1.0000
N21—N22	1.381 (2)	C15—C16	1.556 (2)
N22—C3	1.368 (2)	C15—H15A	0.9900
N22—C23	1.417 (2)	C15—H15B	0.9900
C1—C2	1.498 (2)	C16—C17	1.535 (3)
C1—C10	1.549 (3)	C16—H16A	0.9900
C1—H1A	0.9900	C16—H16B	0.9900
C1—H1B	0.9900	C17—H17	1.0000
C2—C3	1.372 (3)	C18—H18A	0.9800
C2—C20	1.407 (3)	C18—H18B	0.9800
C5—C6	1.519 (2)	C18—H18C	0.9800
C5—C10	1.552 (2)	C19—H19A	0.9800
C5—H5	1.0000	C19—H19B	0.9800
C6—C7	1.534 (2)	C19—H19C	0.9800
C6—H6A	0.9900	C20—H20	0.9500
C6—H6B	0.9900	C23—C24	1.382 (3)
C7—C8	1.529 (2)	C23—C28	1.395 (2)
C7—H7A	0.9900	C24—C25	1.386 (3)
C7—H7B	0.9900	C24—H24	0.9500
C8—C14	1.531 (2)	C25—C26	1.371 (3)
C8—C9	1.544 (2)	C25—H25	0.9500
C8—H8	1.0000	C26—C27	1.376 (3)
C9—C11	1.540 (2)	C27—C28	1.386 (3)
C9—C10	1.556 (2)	C27—H27	0.9500
C9—H9	1.0000	C28—H28	0.9500
C10—C19	1.537 (2)	C30—C31	1.496 (3)
C11—C12	1.529 (2)	C31—H31A	0.9800
C11—H11A	0.9900	C31—H31B	0.9800
C11—H11B	0.9900	C31—H31C	0.9800
C30—O29—C17	117.70 (15)	C17—C13—C18	109.76 (14)
C3—N4—C5	112.06 (14)	C12—C13—C14	108.53 (14)
C3—N4—H4	112.8 (17)	C17—C13—C14	99.01 (13)
C5—N4—H4	115.9 (17)	C18—C13—C14	112.98 (15)
C20—N21—N22	104.58 (14)	C8—C14—C15	120.34 (15)
C3—N22—N21	110.70 (14)	C8—C14—C13	112.67 (13)
C3—N22—C23	130.85 (16)	C15—C14—C13	103.86 (14)
N21—N22—C23	118.36 (14)	C8—C14—H14	106.4
C2—C1—C10	110.20 (14)	C15—C14—H14	106.4
C2—C1—H1A	109.6	C13—C14—H14	106.4
C10—C1—H1A	109.6	C14—C15—C16	104.07 (14)
C2—C1—H1B	109.6	C14—C15—H15A	110.9
C10—C1—H1B	109.6	C16—C15—H15A	110.9
H1A—C1—H1B	108.1	C14—C15—H15B	110.9
C3—C2—C20	104.52 (16)	C16—C15—H15B	110.9
C3—C2—C1	122.25 (16)	H15A—C15—H15B	109.0
C20—C2—C1	133.09 (18)	C17—C16—C15	105.32 (14)
N22—C3—C2	107.70 (15)	C17—C16—H16A	110.7
N22—C3—N4	126.06 (16)	C15—C16—H16A	110.7
C2—C3—N4	126.24 (16)	C17—C16—H16B	110.7
N4—C5—C6	109.10 (14)	C15—C16—H16B	110.7
N4—C5—C10	114.15 (14)	H16A—C16—H16B	108.8
C6—C5—C10	113.04 (14)	O29—C17—C13	108.53 (14)
N4—C5—H5	106.7	O29—C17—C16	115.60 (14)
C6—C5—H5	106.7	C13—C17—C16	105.19 (14)
C10—C5—H5	106.7	O29—C17—H17	109.1
C5—C6—C7	111.51 (14)	C13—C17—H17	109.1
C5—C6—H6A	109.3	C16—C17—H17	109.1
C7—C6—H6A	109.3	C13—C18—H18A	109.5
C5—C6—H6B	109.3	C13—C18—H18B	109.5
C7—C6—H6B	109.3	H18A—C18—H18B	109.5
H6A—C6—H6B	108.0	C13—C18—H18C	109.5
C8—C7—C6	112.55 (14)	H18A—C18—H18C	109.5
C8—C7—H7A	109.1	H18B—C18—H18C	109.5
C6—C7—H7A	109.1	C10—C19—H19A	109.5
C8—C7—H7B	109.1	C10—C19—H19B	109.5
C6—C7—H7B	109.1	H19A—C19—H19B	109.5
H7A—C7—H7B	107.8	C10—C19—H19C	109.5
C7—C8—C14	111.49 (14)	H19A—C19—H19C	109.5
C7—C8—C9	110.06 (14)	H19B—C19—H19C	109.5
C14—C8—C9	108.53 (14)	N21—C20—C2	112.48 (17)
C7—C8—H8	108.9	N21—C20—H20	123.8
C14—C8—H8	108.9	C2—C20—H20	123.8
C9—C8—H8	108.9	C24—C23—C28	120.20 (17)
C11—C9—C8	112.32 (14)	C24—C23—N22	120.65 (16)
C11—C9—C10	112.40 (14)	C28—C23—N22	119.13 (17)
C8—C9—C10	112.81 (14)	C23—C24—C25	120.03 (18)
C11—C9—H9	106.2	C23—C24—H24	120.0
C8—C9—H9	106.2	C25—C24—H24	120.0
C10—C9—H9	106.2	C26—C25—C24	118.66 (19)
C19—C10—C1	109.49 (14)	C26—C25—H25	120.7
C19—C10—C5	110.23 (15)	C24—C25—H25	120.7
C1—C10—C5	107.81 (14)	F26—C26—C25	118.58 (19)
C19—C10—C9	112.52 (14)	F26—C26—C27	118.67 (17)
C1—C10—C9	109.06 (14)	C25—C26—C27	122.75 (18)
C5—C10—C9	107.61 (13)	C26—C27—C28	118.42 (18)
C12—C11—C9	112.61 (15)	C26—C27—H27	120.8
C12—C11—H11A	109.1	C28—C27—H27	120.8
C9—C11—H11A	109.1	C27—C28—C23	119.88 (19)
C12—C11—H11B	109.1	C27—C28—H28	120.1
C9—C11—H11B	109.1	C23—C28—H28	120.1
H11A—C11—H11B	107.8	O30—C30—O29	123.80 (18)
C13—C12—C11	111.04 (14)	O30—C30—C31	124.60 (16)
C13—C12—H12A	109.4	O29—C30—C31	111.60 (18)
C11—C12—H12A	109.4	C30—C31—H31A	109.5
C13—C12—H12B	109.4	C30—C31—H31B	109.5
C11—C12—H12B	109.4	H31A—C31—H31B	109.5
H12A—C12—H12B	108.0	C30—C31—H31C	109.5
C12—C13—C17	115.26 (14)	H31A—C31—H31C	109.5
C12—C13—C18	110.86 (15)	H31B—C31—H31C	109.5
C20—N21—N22—C3	1.5 (2)	C11—C12—C13—C14	57.29 (19)
C20—N21—N22—C23	−175.44 (16)	C7—C8—C14—C15	−57.5 (2)
C10—C1—C2—C3	−17.4 (2)	C9—C8—C14—C15	−178.88 (15)
C10—C1—C2—C20	157.7 (2)	C7—C8—C14—C13	179.47 (15)
N21—N22—C3—C2	−1.4 (2)	C9—C8—C14—C13	58.08 (18)
C23—N22—C3—C2	175.01 (18)	C12—C13—C14—C8	−60.90 (19)
N21—N22—C3—N4	178.87 (17)	C17—C13—C14—C8	178.52 (14)
C23—N22—C3—N4	−4.7 (3)	C18—C13—C14—C8	62.48 (19)
C20—C2—C3—N22	0.7 (2)	C12—C13—C14—C15	167.28 (14)
C1—C2—C3—N22	176.99 (16)	C17—C13—C14—C15	46.70 (16)
C20—C2—C3—N4	−179.56 (18)	C18—C13—C14—C15	−69.34 (17)
C1—C2—C3—N4	−3.3 (3)	C8—C14—C15—C16	−160.61 (15)
C5—N4—C3—N22	171.15 (17)	C13—C14—C15—C16	−33.43 (18)
C5—N4—C3—C2	−8.5 (3)	C14—C15—C16—C17	6.63 (19)
C3—N4—C5—C6	168.82 (15)	C30—O29—C17—C13	−178.63 (15)
C3—N4—C5—C10	41.3 (2)	C30—O29—C17—C16	63.5 (2)
N4—C5—C6—C7	176.49 (15)	C12—C13—C17—O29	77.84 (19)
C10—C5—C6—C7	−55.3 (2)	C18—C13—C17—O29	−48.17 (19)
C5—C6—C7—C8	53.5 (2)	C14—C13—C17—O29	−166.66 (14)
C6—C7—C8—C14	−174.14 (14)	C12—C13—C17—C16	−157.88 (16)
C6—C7—C8—C9	−53.65 (19)	C18—C13—C17—C16	76.11 (18)
C7—C8—C9—C11	−175.10 (15)	C14—C13—C17—C16	−42.38 (17)
C14—C8—C9—C11	−52.84 (18)	C15—C16—C17—O29	142.41 (15)
C7—C8—C9—C10	56.61 (19)	C15—C16—C17—C13	22.73 (19)
C14—C8—C9—C10	178.87 (14)	N22—N21—C20—C2	−1.0 (2)
C2—C1—C10—C19	−74.06 (18)	C3—C2—C20—N21	0.2 (2)
C2—C1—C10—C5	45.88 (19)	C1—C2—C20—N21	−175.47 (19)
C2—C1—C10—C9	162.43 (15)	C3—N22—C23—C24	−27.8 (3)
N4—C5—C10—C19	58.4 (2)	N21—N22—C23—C24	148.36 (19)
C6—C5—C10—C19	−67.10 (17)	C3—N22—C23—C28	153.75 (19)
N4—C5—C10—C1	−61.08 (19)	N21—N22—C23—C28	−30.0 (2)
C6—C5—C10—C1	173.43 (13)	C28—C23—C24—C25	−1.9 (3)
N4—C5—C10—C9	−178.58 (14)	N22—C23—C24—C25	179.70 (17)
C6—C5—C10—C9	55.93 (19)	C23—C24—C25—C26	0.3 (3)
C11—C9—C10—C19	−63.3 (2)	C24—C25—C26—F26	−178.22 (18)
C8—C9—C10—C19	64.90 (19)	C24—C25—C26—C27	1.7 (3)
C11—C9—C10—C1	58.35 (19)	F26—C26—C27—C28	177.94 (17)
C8—C9—C10—C1	−173.41 (14)	C25—C26—C27—C28	−2.0 (3)
C11—C9—C10—C5	175.03 (15)	C26—C27—C28—C23	0.3 (3)
C8—C9—C10—C5	−56.72 (18)	C24—C23—C28—C27	1.6 (3)
C8—C9—C11—C12	52.6 (2)	N22—C23—C28—C27	−179.97 (18)
C10—C9—C11—C12	−178.93 (15)	C17—O29—C30—O30	−4.8 (3)
C9—C11—C12—C13	−54.7 (2)	C17—O29—C30—C31	175.23 (17)
C11—C12—C13—C17	167.21 (15)	C19—C10—C13—C18	0.73 (14)
C11—C12—C13—C18	−67.35 (19)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N4—H4···O30^i	0.90 (3)	2.31 (3)	3.208 (2)	177 (2)
C15—H15B···F26^ii	0.99	2.53	3.455 (2)	155
C20—H20···O30^iii	0.95	2.56	3.477 (3)	162
C25—H25···N21^iv	0.95	2.58	3.399 (3)	145

Symmetry codes: (i) −x+3/2, −y+1, z+1/2; (ii) −x+2, y+1/2, −z+1/2; (iii) x−1/2, −y+1/2, −z; (iv) x+1, y, z.

(II) 2'-(p-fluorophenyl)-4-aza-pyrazolo[4',3':2,3]-5α-androstan-17β-ol

Crystal data

C25H32FN3O	Dx = 1.274 Mg m^−3
Mr = 409.54	Melting point: 513 K
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 2816 reflections
a = 7.0990 (2) Å	θ = 2.0–27.5°
b = 14.8153 (4) Å	µ = 0.08 mm^−1
c = 20.2961 (4) Å	T = 160 K
V = 2134.62 (9) Å^3	Prism, colourless
Z = 4	0.25 × 0.23 × 0.10 mm
F(000) = 880

Data collection

Nonius KappaCCD diffractometer	2390 reflections with I > 2σ(I)
Radiation source: Nonius FR591 sealed tube generator	Rint = 0.063
Horizontally mounted graphite crystal monochromator	θmax = 27.5°, θmin = 2.0°
Detector resolution: 9 pixels mm^-1	h = 0→9
ϕ and ω scans with κ offsets	k = 0→19
34805 measured reflections	l = 0→26
2798 independent reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.037	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.092	w = 1/[σ^2(Fo^2) + (0.0501P)^2 + 0.2133P] where P = (Fo^2 + 2Fc^2)/3
S = 1.04	(Δ/σ)max = 0.001
2797 reflections	Δρmax = 0.22 e Å^−3
282 parameters	Δρmin = −0.17 e Å^−3
0 restraints	Extinction correction: SHELXL, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0114 (15)

Special details

Experimental. Solvent used: acetone Cooling Device: Oxford Cryosystems Cryostream 700 Crystal mount: glued on a glass fibre Mosaicity (°.): 0.536 (1) Frames collected: 229 Seconds exposure per frame: 96 Degrees rotation per frame: 1.6 Crystal-Detector distance (mm): 30.50

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq
F26	−0.4329 (2)	0.28024 (10)	0.44290 (7)	0.0603 (5)
O17	0.5167 (2)	−0.03226 (10)	−0.21548 (7)	0.0341 (4)
H17A	0.583 (4)	0.0113 (17)	−0.2267 (12)	0.047 (7)*
N4	0.0383 (2)	0.17335 (11)	0.17876 (8)	0.0260 (4)
H4	0.022 (3)	0.1285 (14)	0.2068 (10)	0.027 (6)*
N21	0.2522 (2)	0.36611 (11)	0.25569 (8)	0.0308 (4)
N22	0.1176 (2)	0.29911 (10)	0.25161 (7)	0.0266 (4)
C1	0.3892 (3)	0.22984 (13)	0.10721 (9)	0.0272 (4)
H1A	0.5270	0.2213	0.1115	0.033*
H1B	0.3661	0.2702	0.0692	0.033*
C2	0.3141 (3)	0.27322 (13)	0.16880 (9)	0.0256 (4)
C3	0.1539 (3)	0.24264 (12)	0.19971 (9)	0.0247 (4)
C5	0.0807 (3)	0.14550 (13)	0.11059 (9)	0.0238 (4)
H5	0.0293	0.1937	0.0811	0.029*
C6	−0.0281 (3)	0.05996 (13)	0.09519 (9)	0.0275 (4)
H6A	−0.1627	0.0688	0.1062	0.033*
H6B	0.0207	0.0098	0.1225	0.033*
C7	−0.0092 (3)	0.03568 (13)	0.02240 (9)	0.0275 (4)
H7A	−0.0736	0.0822	−0.0044	0.033*
H7B	−0.0728	−0.0227	0.0143	0.033*
C8	0.1963 (3)	0.02866 (13)	0.00040 (9)	0.0230 (4)
H8	0.2555	−0.0249	0.0220	0.028*
C9	0.3076 (3)	0.11456 (12)	0.01982 (8)	0.0224 (4)
H9	0.2460	0.1659	−0.0039	0.027*
C10	0.2941 (3)	0.13698 (12)	0.09439 (9)	0.0227 (4)
C11	0.5106 (3)	0.11018 (14)	−0.00588 (9)	0.0276 (4)
H11A	0.5784	0.0611	0.0172	0.033*
H11B	0.5752	0.1677	0.0045	0.033*
C12	0.5209 (3)	0.09347 (13)	−0.08074 (9)	0.0273 (4)
H12A	0.4683	0.1463	−0.1043	0.033*
H12B	0.6542	0.0866	−0.0941	0.033*
C13	0.4116 (3)	0.00899 (12)	−0.10018 (9)	0.0236 (4)
C14	0.2094 (3)	0.01776 (13)	−0.07426 (9)	0.0250 (4)
H14	0.1585	0.0749	−0.0935	0.030*
C15	0.1032 (3)	−0.05911 (15)	−0.10820 (10)	0.0338 (5)
H15A	−0.0321	−0.0443	−0.1132	0.041*
H15B	0.1153	−0.1161	−0.0831	0.041*
C16	0.2015 (3)	−0.06656 (15)	−0.17639 (10)	0.0357 (5)
H16A	0.2470	−0.1289	−0.1839	0.043*
H16B	0.1129	−0.0503	−0.2122	0.043*
C17	0.3678 (3)	−0.00010 (13)	−0.17446 (9)	0.0287 (5)
H17	0.3244	0.0597	−0.1915	0.034*
C18	0.5122 (3)	−0.07648 (14)	−0.07613 (10)	0.0323 (5)
H18A	0.6295	−0.0846	−0.1009	0.048*
H18B	0.4304	−0.1289	−0.0830	0.048*
H18C	0.5411	−0.0706	−0.0291	0.048*
C19	0.3873 (3)	0.06559 (14)	0.13813 (9)	0.0300 (4)
H19A	0.3335	0.0062	0.1282	0.045*
H19B	0.3648	0.0803	0.1845	0.045*
H19C	0.5231	0.0646	0.1296	0.045*
C20	0.3671 (3)	0.34977 (13)	0.20530 (9)	0.0294 (4)
H20	0.4736	0.3860	0.1951	0.035*
C23	−0.0252 (3)	0.29339 (13)	0.30082 (9)	0.0277 (5)
C24	−0.2066 (3)	0.26865 (14)	0.28366 (10)	0.0337 (5)
H24	−0.2361	0.2546	0.2392	0.040*
C25	−0.3454 (3)	0.26446 (15)	0.33172 (10)	0.0391 (5)
H25	−0.4708	0.2479	0.3208	0.047*
C26	−0.2969 (4)	0.28488 (14)	0.39547 (11)	0.0402 (6)
C27	−0.1186 (4)	0.30918 (14)	0.41352 (10)	0.0391 (6)
H27	−0.0901	0.3227	0.4582	0.047*
C28	0.0200 (4)	0.31379 (13)	0.36565 (10)	0.0344 (5)
H28	0.1448	0.3308	0.3771	0.041*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
F26	0.0734 (11)	0.0587 (9)	0.0487 (8)	−0.0076 (8)	0.0388 (8)	−0.0083 (7)
O17	0.0403 (9)	0.0319 (8)	0.0299 (7)	−0.0066 (7)	0.0126 (7)	−0.0066 (6)
N4	0.0298 (9)	0.0258 (8)	0.0224 (8)	−0.0020 (7)	0.0049 (7)	−0.0001 (7)
N21	0.0341 (10)	0.0297 (8)	0.0287 (9)	−0.0022 (8)	−0.0011 (8)	−0.0030 (7)
N22	0.0296 (9)	0.0248 (8)	0.0254 (8)	0.0008 (7)	0.0011 (7)	−0.0017 (7)
C1	0.0279 (10)	0.0313 (10)	0.0224 (9)	−0.0013 (9)	0.0013 (8)	−0.0028 (8)
C2	0.0272 (10)	0.0272 (10)	0.0224 (9)	0.0011 (8)	−0.0007 (8)	0.0006 (7)
C3	0.0284 (11)	0.0251 (9)	0.0207 (9)	0.0043 (8)	−0.0013 (8)	0.0019 (7)
C5	0.0261 (10)	0.0251 (9)	0.0201 (9)	0.0008 (8)	0.0016 (8)	0.0002 (7)
C6	0.0242 (10)	0.0303 (10)	0.0279 (10)	−0.0028 (9)	0.0031 (8)	−0.0031 (8)
C7	0.0248 (10)	0.0304 (10)	0.0273 (10)	−0.0023 (9)	0.0018 (8)	−0.0043 (8)
C8	0.0232 (10)	0.0234 (9)	0.0225 (9)	0.0002 (8)	0.0008 (8)	0.0005 (7)
C9	0.0239 (10)	0.0236 (9)	0.0196 (9)	0.0005 (8)	0.0003 (8)	0.0007 (7)
C10	0.0221 (10)	0.0260 (9)	0.0201 (9)	−0.0004 (8)	0.0019 (8)	−0.0002 (7)
C11	0.0261 (11)	0.0329 (10)	0.0237 (9)	−0.0050 (9)	0.0027 (8)	−0.0051 (8)
C12	0.0305 (11)	0.0283 (10)	0.0232 (9)	−0.0037 (9)	0.0060 (8)	−0.0018 (8)
C13	0.0265 (10)	0.0233 (9)	0.0210 (9)	−0.0025 (8)	0.0023 (8)	−0.0010 (7)
C14	0.0265 (10)	0.0266 (9)	0.0219 (9)	−0.0002 (9)	−0.0010 (8)	−0.0017 (8)
C15	0.0308 (11)	0.0410 (12)	0.0295 (10)	−0.0073 (10)	0.0039 (9)	−0.0086 (9)
C16	0.0351 (11)	0.0422 (12)	0.0298 (10)	−0.0064 (11)	0.0033 (9)	−0.0097 (9)
C17	0.0329 (11)	0.0309 (10)	0.0222 (9)	−0.0007 (9)	0.0027 (9)	−0.0037 (8)
C18	0.0319 (12)	0.0315 (10)	0.0334 (11)	0.0047 (9)	0.0024 (9)	−0.0015 (8)
C19	0.0312 (11)	0.0356 (11)	0.0233 (9)	0.0029 (10)	0.0001 (9)	0.0018 (8)
C20	0.0297 (11)	0.0297 (10)	0.0288 (10)	−0.0027 (9)	0.0003 (9)	−0.0011 (8)
C23	0.0354 (12)	0.0219 (9)	0.0258 (10)	0.0054 (9)	0.0052 (9)	−0.0003 (8)
C24	0.0374 (12)	0.0354 (11)	0.0282 (10)	0.0027 (10)	0.0049 (9)	−0.0011 (9)
C25	0.0369 (13)	0.0390 (12)	0.0414 (12)	0.0018 (10)	0.0118 (10)	−0.0006 (10)
C26	0.0554 (15)	0.0301 (11)	0.0352 (12)	0.0030 (11)	0.0224 (11)	−0.0014 (9)
C27	0.0641 (17)	0.0278 (10)	0.0254 (10)	0.0024 (12)	0.0079 (11)	−0.0040 (8)
C28	0.0488 (14)	0.0265 (10)	0.0280 (10)	0.0028 (10)	0.0038 (10)	−0.0030 (8)

Geometric parameters (Å, º)

F26—C26	1.365 (3)	C11—H11B	0.9900
O17—C17	1.428 (2)	C12—C13	1.524 (3)
O17—H17A	0.83 (3)	C12—H12A	0.9900
N4—C3	1.381 (2)	C12—H12B	0.9900
N4—C5	1.475 (2)	C13—C18	1.534 (3)
N4—H4	0.88 (2)	C13—C14	1.534 (3)
N21—C20	1.330 (3)	C13—C17	1.545 (3)
N21—N22	1.380 (2)	C14—C15	1.530 (3)
N22—C3	1.370 (2)	C14—H14	1.0000
N22—C23	1.426 (3)	C15—C16	1.554 (3)
C1—C2	1.503 (3)	C15—H15A	0.9900
C1—C10	1.555 (3)	C15—H15B	0.9900
C1—H1A	0.9900	C16—C17	1.538 (3)
C1—H1B	0.9900	C16—H16A	0.9900
C2—C3	1.375 (3)	C16—H16B	0.9900
C2—C20	1.406 (3)	C17—H17	1.0000
C5—C6	1.517 (3)	C18—H18A	0.9800
C5—C10	1.555 (3)	C18—H18B	0.9800
C5—H5	1.0000	C18—H18C	0.9800
C6—C7	1.526 (3)	C19—H19A	0.9800
C6—H6A	0.9900	C19—H19B	0.9800
C6—H6B	0.9900	C19—H19C	0.9800
C7—C8	1.529 (3)	C20—H20	0.9500
C7—H7A	0.9900	C23—C24	1.384 (3)
C7—H7B	0.9900	C23—C28	1.388 (3)
C8—C14	1.527 (2)	C24—C25	1.388 (3)
C8—C9	1.549 (3)	C24—H24	0.9500
C8—H8	1.0000	C25—C26	1.373 (3)
C9—C11	1.534 (3)	C25—H25	0.9500
C9—C10	1.552 (2)	C26—C27	1.366 (4)
C9—H9	1.0000	C27—C28	1.384 (3)
C10—C19	1.531 (3)	C27—H27	0.9500
C11—C12	1.541 (2)	C28—H28	0.9500
C11—H11A	0.9900
C17—O17—H17A	108.6 (19)	C11—C12—H12B	109.4
C3—N4—C5	112.05 (15)	H12A—C12—H12B	108.0
C3—N4—H4	116.1 (14)	C12—C13—C18	111.02 (16)
C5—N4—H4	114.9 (13)	C12—C13—C14	108.53 (15)
C20—N21—N22	104.33 (15)	C18—C13—C14	113.36 (16)
C3—N22—N21	110.80 (16)	C12—C13—C17	115.25 (15)
C3—N22—C23	129.52 (17)	C18—C13—C17	109.41 (15)
N21—N22—C23	119.54 (15)	C14—C13—C17	98.82 (15)
C2—C1—C10	111.30 (16)	C8—C14—C15	119.70 (17)
C2—C1—H1A	109.4	C8—C14—C13	113.97 (16)
C10—C1—H1A	109.4	C15—C14—C13	104.12 (15)
C2—C1—H1B	109.4	C8—C14—H14	106.0
C10—C1—H1B	109.4	C15—C14—H14	106.0
H1A—C1—H1B	108.0	C13—C14—H14	106.0
C3—C2—C20	104.27 (17)	C14—C15—C16	103.44 (16)
C3—C2—C1	122.13 (18)	C14—C15—H15A	111.1
C20—C2—C1	133.47 (19)	C16—C15—H15A	111.1
N22—C3—C2	107.77 (17)	C14—C15—H15B	111.1
N22—C3—N4	125.38 (18)	C16—C15—H15B	111.1
C2—C3—N4	126.55 (17)	H15A—C15—H15B	109.0
N4—C5—C6	108.85 (15)	C17—C16—C15	106.05 (15)
N4—C5—C10	114.82 (16)	C17—C16—H16A	110.5
C6—C5—C10	112.62 (16)	C15—C16—H16A	110.5
N4—C5—H5	106.7	C17—C16—H16B	110.5
C6—C5—H5	106.7	C15—C16—H16B	110.5
C10—C5—H5	106.7	H16A—C16—H16B	108.7
C5—C6—C7	110.59 (16)	O17—C17—C16	109.87 (15)
C5—C6—H6A	109.5	O17—C17—C13	116.68 (17)
C7—C6—H6A	109.5	C16—C17—C13	103.61 (15)
C5—C6—H6B	109.5	O17—C17—H17	108.8
C7—C6—H6B	109.5	C16—C17—H17	108.8
H6A—C6—H6B	108.1	C13—C17—H17	108.8
C6—C7—C8	112.48 (16)	C13—C18—H18A	109.5
C6—C7—H7A	109.1	C13—C18—H18B	109.5
C8—C7—H7A	109.1	H18A—C18—H18B	109.5
C6—C7—H7B	109.1	C13—C18—H18C	109.5
C8—C7—H7B	109.1	H18A—C18—H18C	109.5
H7A—C7—H7B	107.8	H18B—C18—H18C	109.5
C14—C8—C7	110.81 (16)	C10—C19—H19A	109.5
C14—C8—C9	107.96 (15)	C10—C19—H19B	109.5
C7—C8—C9	110.88 (15)	H19A—C19—H19B	109.5
C14—C8—H8	109.0	C10—C19—H19C	109.5
C7—C8—H8	109.0	H19A—C19—H19C	109.5
C9—C8—H8	109.0	H19B—C19—H19C	109.5
C11—C9—C8	110.98 (15)	N21—C20—C2	112.82 (19)
C11—C9—C10	113.49 (16)	N21—C20—H20	123.6
C8—C9—C10	113.10 (15)	C2—C20—H20	123.6
C11—C9—H9	106.2	C24—C23—C28	120.8 (2)
C8—C9—H9	106.2	C24—C23—N22	120.09 (17)
C10—C9—H9	106.2	C28—C23—N22	119.1 (2)
C19—C10—C9	113.00 (15)	C23—C24—C25	119.72 (19)
C19—C10—C1	109.06 (16)	C23—C24—H24	120.1
C9—C10—C1	109.01 (14)	C25—C24—H24	120.1
C19—C10—C5	110.75 (16)	C26—C25—C24	118.3 (2)
C9—C10—C5	106.48 (15)	C26—C25—H25	120.8
C1—C10—C5	108.43 (16)	C24—C25—H25	120.8
C9—C11—C12	112.73 (16)	F26—C26—C27	118.7 (2)
C9—C11—H11A	109.0	F26—C26—C25	118.5 (2)
C12—C11—H11A	109.0	C27—C26—C25	122.9 (2)
C9—C11—H11B	109.0	C26—C27—C28	118.9 (2)
C12—C11—H11B	109.0	C26—C27—H27	120.5
H11A—C11—H11B	107.8	C28—C27—H27	120.5
C13—C12—C11	111.29 (15)	C27—C28—C23	119.4 (2)
C13—C12—H12A	109.4	C27—C28—H28	120.3
C11—C12—H12A	109.4	C23—C28—H28	120.3
C13—C12—H12B	109.4
C20—N21—N22—C3	0.8 (2)	C11—C12—C13—C18	−70.6 (2)
C20—N21—N22—C23	176.90 (17)	C11—C12—C13—C14	54.6 (2)
C10—C1—C2—C3	−13.4 (3)	C11—C12—C13—C17	164.34 (17)
C10—C1—C2—C20	171.3 (2)	C7—C8—C14—C15	−55.1 (2)
N21—N22—C3—C2	−0.4 (2)	C9—C8—C14—C15	−176.73 (17)
C23—N22—C3—C2	−175.97 (18)	C7—C8—C14—C13	−179.25 (15)
N21—N22—C3—N4	−174.40 (17)	C9—C8—C14—C13	59.1 (2)
C23—N22—C3—N4	10.1 (3)	C12—C13—C14—C8	−59.3 (2)
C20—C2—C3—N22	−0.2 (2)	C18—C13—C14—C8	64.5 (2)
C1—C2—C3—N22	−176.63 (17)	C17—C13—C14—C8	−179.83 (15)
C20—C2—C3—N4	173.72 (18)	C12—C13—C14—C15	168.52 (15)
C1—C2—C3—N4	−2.7 (3)	C18—C13—C14—C15	−67.65 (18)
C5—N4—C3—N22	160.74 (17)	C17—C13—C14—C15	48.03 (18)
C5—N4—C3—C2	−12.1 (3)	C8—C14—C15—C16	−162.06 (18)
C3—N4—C5—C6	170.72 (16)	C13—C14—C15—C16	−33.3 (2)
C3—N4—C5—C10	43.4 (2)	C14—C15—C16—C17	5.1 (2)
N4—C5—C6—C7	172.43 (16)	C15—C16—C17—O17	149.88 (17)
C10—C5—C6—C7	−59.0 (2)	C15—C16—C17—C13	24.5 (2)
C5—C6—C7—C8	54.4 (2)	C12—C13—C17—O17	79.8 (2)
C6—C7—C8—C14	−171.87 (16)	C18—C13—C17—O17	−46.1 (2)
C6—C7—C8—C9	−52.0 (2)	C14—C13—C17—O17	−164.82 (16)
C14—C8—C9—C11	−55.0 (2)	C12—C13—C17—C16	−159.34 (17)
C7—C8—C9—C11	−176.55 (15)	C18—C13—C17—C16	74.7 (2)
C14—C8—C9—C10	176.14 (16)	C14—C13—C17—C16	−43.95 (18)
C7—C8—C9—C10	54.6 (2)	N22—N21—C20—C2	−1.0 (2)
C11—C9—C10—C19	−62.2 (2)	C3—C2—C20—N21	0.7 (2)
C8—C9—C10—C19	65.4 (2)	C1—C2—C20—N21	176.6 (2)
C11—C9—C10—C1	59.2 (2)	C3—N22—C23—C24	−41.6 (3)
C8—C9—C10—C1	−173.21 (16)	N21—N22—C23—C24	143.20 (19)
C11—C9—C10—C5	176.00 (16)	C3—N22—C23—C28	139.1 (2)
C8—C9—C10—C5	−56.4 (2)	N21—N22—C23—C28	−36.1 (3)
C2—C1—C10—C19	−80.1 (2)	C28—C23—C24—C25	0.2 (3)
C2—C1—C10—C9	156.15 (16)	N22—C23—C24—C25	−179.11 (18)
C2—C1—C10—C5	40.6 (2)	C23—C24—C25—C26	−0.3 (3)
N4—C5—C10—C19	61.0 (2)	C24—C25—C26—F26	−179.58 (18)
C6—C5—C10—C19	−64.3 (2)	C24—C25—C26—C27	0.1 (3)
N4—C5—C10—C9	−175.77 (14)	F26—C26—C27—C28	179.85 (18)
C6—C5—C10—C9	58.9 (2)	C25—C26—C27—C28	0.2 (3)
N4—C5—C10—C1	−58.6 (2)	C26—C27—C28—C23	−0.2 (3)
C6—C5—C10—C1	176.06 (14)	C24—C23—C28—C27	0.1 (3)
C8—C9—C11—C12	54.7 (2)	N22—C23—C28—C27	179.39 (18)
C10—C9—C11—C12	−176.59 (15)	C19—C10—C13—C18	1.36 (16)
C9—C11—C12—C13	−54.8 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N4—H4···O17^i	0.88 (2)	2.14 (2)	3.021 (2)	172.7 (18)
O17—H17A···N21^ii	0.83 (3)	2.26 (3)	3.086 (2)	177 (3)

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