tert-Butyl (3S,6R,9R)-(5-oxo-3-{[1(R)-phenyl­ethyl]­carbamoyl}-1,2,3,5,6,7,8,8a-octa­hydro­indolizin-6-yl)­carbamate monohydrate at 95 K

The asymmetric unit of the title compound, C₂₂H₃₁N₃O₄·H₂O, incorporates one water mol­ecule, which is hydrogen bonded to the 3-oxo O atom of the indolizidinone system. The two rings of the peptidomimetic mol­ecule are trans-fused, with the six-membered ring having a slightly distorted half-chair conformation and the five-membered ring having a perfect envelope conformation. The structure is stabilized by intermolecular O—H...O interactions between the water and adjacent peptide mol­ecules, and by N—H...O interactions between the peptide mol­ecules, which link the mol­ecules into infinite chains.

S1. Comment

Indolizidinone-type 6,5-fused bicyclic lactams are of considerable pharmaceutical interest, since they can act as dipeptide mimics (Kim et al., 1996; Colombo et al., 1998; Angiolini et al., 2000). The synthesis of so-called peptidomimetic molecules has been a very active and productive field of research in drug design (Hanessian et al., 1997). The rationale for the development of peptide analogues is that these molecules have the same biological effects as natural peptides but, at the same time, are metabolically more stable. Of particular interest has been the replacement of reverse-turn dipeptide motifs with constrained molecules that reproduce their conformational features (Kahn, 1993). 6,5- and 7,5-fused 2-oxo-1-azabicyclo[X.3.0]alkane amino acids can be regarded as conformationally resticted substitutes for Ala-Pro and Phe-Pro dipeptide units; their conformations, studied using a combination of computer modelling with ¹H NMR and FT–IR spectroscopy (Belvisi et al., 2000), have been shown to meet specific criteria, so they can be used to replace the central (i+1 and i+2) residues of β-turns.

To validate the conformational information obtained by these methods, the structure determination of the title compound, (I), a synthetic derivative of a 6,5-fused bicyclic lactam whose crystallinity allows an X-ray crystallographic analysis, has been undertaken. A preliminary data collection at room temperature showed that the crystal had a very low diffracting power. To increase the percentage of significant data, the temperature of the experiment was reduced to 95 K. The asymmetric unit of (I) comprises one molecule of tert-butyl (3S,6R,9R)-(5-oxo-3-{[1(R)-phenylethyl]carbamoyl}- 1,2,3,5,6,7,8,8a-octahydroindolizin-6-yl)carbamate and one water molecule (Fig. 1), which interact through an O—H···O hydrogen bond. The absolute configuration of (I) was based on the known configuration of the starting material (Angiolini et al., 2000).

The six-membered ring of the indolizidinone system has a quite distorted half-chair conformation, with puckering parameters (Cremer & Pople, 1975) Q = 0.522 (2) Å, θ = 46.2 (3)° and ϕ = 216.4 (4)° for the atom sequence N2—C5—C6—C7—C8—C9. Atoms C7 and C8 are 0.325 (4) and -0.467 (4) Å, respectively, from the mean plane defined by atoms C9, N2, C5 and C6, and the r.m.s. deviation of these latter four atoms from their plane is 0.024 Å. The amido substituent at C6 (6R) is oriented equatorially, in agreement with the orientation reported for another bicyclic lactam (Kim et al., 1996). The same authors also indicate that the six-membered ring of the bicycle adopts a pseudo-chair conformation, while Hua et al. (1995) found that the six-membered lactam ring in a derivative of an octahydro-5-indolizinone could be described as having a distorted envelope conformation. However, we calculated the puckering parameters for the six-membered ring in these two literature structures and found them to be quite similar [Q = 0.479 and 0.531 (6) Å; θ = 40.5 and 55.3 (5)°; ϕ = 229.2 and 215.6 (8)°, respectively] to those for the title compound, which are close to the ideal values for a half-chair conformation (Cremer & Pople, 1975). Hua et al. (1995) state that `normally, the six-membered lactam ring assumes a distorted chair conformation owing to the tendency of the amide bond to be planar' and this is in agreement with the perfect chair conformation reported for different indolizidine moieties (Koh et al., 1993; Fleming et al., 1996; Mukhopadhyyay, 1998). The five-membered ring adopts an almost perfect envelope conformation for the atom sequence C9—C1—C2—C3—N2; the puckering parameters are q = 0.388 (2) Å and ϕ = 217.1 (4)° (the nearest ideal value for an envelope amounts to ϕ = 216°), and atom C1 is 0.596 (4) Å from the mean plane defined by atoms C2, C3, N2 and C9 (the r.m.s. deviation of these four atoms from the plane is 0.002 Å). The same conformation has been found both in indolizidinone (Hua et al., 1995) and indolizidine (Koh et al., 1993; Fleming et al., 1996; Garofano et al., 1998; Mukhopadhyyay, 1998) systems. The two rings are trans-fused (Table 1).

The observed bond distances and angles for the three amide bonds in the molecule are within the expected range derived from previously reported data (Allen et al., 1987). The value found for the N2—C9 distance is in good agreement with other values reported for this bond in the same environment, which range from 1.469 (2) (Garofano et al., 1998) to 1.479 (3) Å (Koh et al., 1993).

The geometric parameters of the hydrogen bonds are given in Table 2. Intermolecular O—H···O and N—H···O hydrogen bonds link the molecules into extended chains, which run parallel to the a axis, as shown in Fig. 2. Within the chain, adjacent peptide molecules are parallel but in a head-to-tail arrangement, as each N—H interacts with the amide O at the opposite end of the next molecule. The water molecule also links ajacent peptide molecules within the chain. In addition, one weaker C—H···O interaction is present.

S2. Experimental

The title compound was synthesized according to a previously reported procedure (Angiolini et al., 2000) followed by protective group manipulation. Suitable single crystals of (I) were obtained by recrystallization from diethyl ether.

S3. Refinement

Due to the absence of any significant anomalous scatterers in the compound, the absolute configuration could not be determined and Friedel opposites were merged before the final refinement. The absolute configuration of the model was assigned to match the configuration of the chiral centres known from the synthesis. Atoms H1W and H2W were located from difference Fourier maps and refined isotropically. All remaining H atoms were treated as riding atoms (C—H = 0.95–1.00 Å), with U_iso(H) = 1.2U_eq(parent atom).

Computing details

Data collection: SMART (Siemens, 1996); cell refinement: SAINT (Siemens, 1996); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPIII (Burnett & Johnson, 1996); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. The molecular structure of (I) with the atom-numbering scheme. The intramolecular hydrogen bond is shown as a dashed line and displacement ellipsoids are drawn at the 40% probability level.
	Fig. 2. Packing diagram viewed down the b axis. Intermolecular O—H···O and N—H···O hydrogen bonds are shown as dashed lines.

tert-Butyl (3S,6R,9R)-(5-oxo-3-{N-[1(R)-phenylethyl]carbamoyl}- 1,2,3,5,6,7,8,8a-octahydroindolizin-6-yl)carbamate monohydrate

Crystal data

C22H31N3O4·H2O	F(000) = 904
Mr = 419.51	Dx = 1.211 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 4199 reflections
a = 8.520 (2) Å	θ = 2.4–20.6°
b = 12.095 (2) Å	µ = 0.09 mm^−1
c = 22.323 (5) Å	T = 95 K
V = 2300.4 (8) Å^3	Prism, colourless
Z = 4	0.55 × 0.10 × 0.06 mm

Data collection

Bruker SMART CCD area-detector diffractometer	2933 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.047
Graphite monochromator	θmax = 27.5°, θmin = 1.8°
ω scans	h = −11→11
23342 measured reflections	k = −15→15
2992 independent reflections	l = −29→29

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.048	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.109	H atoms treated by a mixture of independent and constrained refinement
S = 1.15	w = 1/[σ^2(Fo^2) + (0.0371P)^2 + 1.2606P] where P = (Fo^2 + 2Fc^2)/3
2992 reflections	(Δ/σ)max = 0.001
293 parameters	Δρmax = 0.34 e Å^−3
0 restraints	Δρmin = −0.22 e Å^−3

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 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
O1W	0.5635 (3)	0.8447 (2)	0.62571 (10)	0.0391 (6)
H1W	0.530 (5)	0.829 (3)	0.5923 (19)	0.039 (11)*
H2W	0.632 (7)	0.796 (5)	0.635 (2)	0.087 (18)*
N1	0.4972 (2)	0.95998 (16)	0.38705 (9)	0.0136 (4)
H1	0.5986	0.9727	0.3839	0.020*
N2	0.5453 (2)	0.67431 (16)	0.42135 (9)	0.0140 (4)
N3	0.5147 (3)	0.58712 (17)	0.57343 (9)	0.0151 (4)
H3	0.6041	0.6215	0.5800	0.023*
O1	0.3110 (2)	0.82555 (14)	0.39133 (8)	0.0172 (4)
O2	0.5352 (2)	0.77803 (14)	0.50429 (7)	0.0192 (4)
O3	0.3180 (2)	0.48716 (15)	0.61571 (8)	0.0182 (4)
O4	0.5353 (2)	0.54085 (15)	0.66798 (7)	0.0188 (4)
C1	0.4920 (3)	0.6150 (2)	0.32452 (11)	0.0187 (5)
H1A	0.3786	0.6318	0.3211	0.028*
H1B	0.5214	0.5613	0.2930	0.028*
C3	0.5821 (3)	0.7700 (2)	0.38392 (10)	0.0139 (5)
H3A	0.6849	0.8034	0.3958	0.021*
C2	0.5910 (3)	0.7205 (2)	0.32018 (11)	0.0192 (5)
H2A	0.5468	0.7721	0.2902	0.029*
H2B	0.7008	0.7030	0.3091	0.029*
C4	0.4493 (3)	0.85503 (19)	0.38888 (10)	0.0123 (4)
C5	0.5158 (3)	0.6883 (2)	0.47978 (11)	0.0141 (5)
C6	0.4467 (3)	0.58923 (19)	0.51374 (10)	0.0149 (5)
H6	0.3315	0.6025	0.5183	0.022*
C7	0.4671 (4)	0.4802 (2)	0.48117 (11)	0.0213 (5)
H7A	0.4021	0.4227	0.5007	0.032*
H7B	0.5782	0.4566	0.4833	0.032*
C8	0.4181 (4)	0.4922 (2)	0.41572 (11)	0.0224 (6)
H8A	0.4213	0.4194	0.3954	0.034*
H8B	0.3098	0.5215	0.4131	0.034*
C9	0.5319 (3)	0.57118 (19)	0.38627 (11)	0.0173 (5)
H9	0.6374	0.5352	0.3845	0.026*
C10	0.4445 (3)	0.5341 (2)	0.61869 (11)	0.0148 (5)
C11	0.4874 (3)	0.4905 (2)	0.72518 (11)	0.0181 (5)
C12	0.4694 (4)	0.3660 (2)	0.71804 (12)	0.0292 (7)
H12A	0.3759	0.3501	0.6939	0.044*
H12B	0.4581	0.3318	0.7576	0.044*
H12C	0.5624	0.3359	0.6980	0.044*
C13	0.3390 (3)	0.5452 (2)	0.74875 (12)	0.0228 (6)
H13A	0.3530	0.6256	0.7491	0.034*
H13B	0.3181	0.5191	0.7895	0.034*
H13C	0.2504	0.5261	0.7228	0.034*
C14	0.6265 (3)	0.5177 (3)	0.76509 (12)	0.0253 (6)
H14A	0.6352	0.5981	0.7695	0.038*
H14B	0.7228	0.4887	0.7470	0.038*
H14C	0.6111	0.4839	0.8046	0.038*
C15	0.3920 (3)	1.0549 (2)	0.39002 (11)	0.0159 (5)
H15	0.2869	1.0319	0.3745	0.024*
C16	0.4570 (3)	1.1449 (2)	0.34893 (11)	0.0203 (5)
H16A	0.4684	1.1154	0.3083	0.030*
H16B	0.5596	1.1691	0.3638	0.030*
H16C	0.3846	1.2079	0.3484	0.030*
C17	0.3719 (3)	1.0968 (2)	0.45395 (11)	0.0160 (5)
C18	0.2770 (3)	1.1893 (2)	0.46445 (13)	0.0203 (5)
H18	0.2246	1.2239	0.4319	0.030*
C19	0.2587 (3)	1.2311 (2)	0.52195 (14)	0.0251 (6)
H19	0.1939	1.2939	0.5285	0.038*
C20	0.3344 (4)	1.1816 (2)	0.56971 (13)	0.0266 (6)
H20	0.3228	1.2108	0.6090	0.040*
C21	0.4271 (3)	1.0896 (2)	0.56009 (12)	0.0247 (6)
H21	0.4785	1.0551	0.5929	0.037*
C22	0.4456 (3)	1.0470 (2)	0.50242 (11)	0.0191 (5)
H22	0.5091	0.9834	0.4963	0.029*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1W	0.0586 (16)	0.0380 (13)	0.0208 (11)	0.0226 (13)	−0.0072 (11)	−0.0116 (9)
N1	0.0115 (9)	0.0139 (9)	0.0155 (9)	0.0013 (8)	0.0007 (8)	0.0006 (8)
N2	0.0152 (10)	0.0124 (9)	0.0144 (9)	−0.0002 (8)	0.0012 (8)	0.0013 (8)
N3	0.0147 (10)	0.0183 (10)	0.0125 (9)	−0.0026 (9)	−0.0034 (8)	0.0042 (8)
O1	0.0155 (8)	0.0152 (8)	0.0209 (9)	0.0004 (7)	0.0010 (7)	0.0016 (7)
O2	0.0327 (10)	0.0141 (8)	0.0108 (7)	−0.0016 (8)	−0.0009 (8)	0.0002 (7)
O3	0.0139 (8)	0.0224 (9)	0.0182 (8)	−0.0003 (7)	0.0012 (7)	0.0052 (7)
O4	0.0152 (8)	0.0282 (9)	0.0130 (8)	−0.0010 (8)	−0.0015 (7)	0.0062 (7)
C1	0.0250 (13)	0.0174 (11)	0.0137 (11)	−0.0012 (11)	0.0019 (10)	−0.0036 (9)
C3	0.0140 (11)	0.0149 (10)	0.0128 (11)	0.0016 (9)	0.0016 (9)	0.0017 (9)
C2	0.0261 (14)	0.0189 (12)	0.0125 (11)	0.0012 (11)	0.0037 (10)	−0.0014 (10)
C4	0.0147 (11)	0.0149 (10)	0.0072 (9)	0.0012 (9)	0.0009 (9)	0.0007 (8)
C5	0.0124 (11)	0.0160 (11)	0.0137 (10)	0.0020 (9)	−0.0025 (9)	0.0022 (9)
C6	0.0131 (11)	0.0165 (11)	0.0149 (11)	0.0005 (10)	−0.0024 (9)	0.0032 (9)
C7	0.0311 (14)	0.0140 (11)	0.0189 (11)	−0.0043 (11)	−0.0003 (11)	0.0032 (9)
C8	0.0324 (15)	0.0177 (12)	0.0170 (12)	−0.0093 (12)	−0.0009 (11)	−0.0012 (10)
C9	0.0220 (12)	0.0132 (11)	0.0166 (11)	0.0028 (10)	0.0007 (10)	−0.0021 (9)
C10	0.0141 (11)	0.0146 (11)	0.0158 (11)	0.0042 (9)	−0.0008 (9)	0.0019 (9)
C11	0.0213 (12)	0.0217 (12)	0.0114 (10)	0.0010 (11)	0.0013 (10)	0.0049 (9)
C12	0.0480 (19)	0.0208 (13)	0.0187 (12)	0.0071 (14)	0.0003 (13)	0.0031 (10)
C13	0.0237 (14)	0.0255 (13)	0.0192 (12)	0.0001 (12)	0.0042 (11)	−0.0012 (11)
C14	0.0235 (14)	0.0361 (16)	0.0162 (12)	0.0030 (13)	−0.0034 (11)	0.0051 (11)
C15	0.0160 (11)	0.0129 (11)	0.0189 (12)	−0.0004 (9)	−0.0029 (10)	0.0005 (10)
C16	0.0277 (14)	0.0157 (11)	0.0176 (12)	0.0001 (11)	−0.0001 (11)	0.0021 (9)
C17	0.0167 (12)	0.0116 (11)	0.0197 (12)	−0.0037 (10)	0.0040 (10)	−0.0012 (9)
C18	0.0196 (12)	0.0139 (11)	0.0275 (14)	−0.0014 (11)	0.0045 (11)	0.0036 (10)
C19	0.0269 (14)	0.0132 (11)	0.0353 (15)	−0.0007 (11)	0.0115 (12)	−0.0036 (11)
C20	0.0327 (15)	0.0249 (13)	0.0222 (13)	−0.0049 (13)	0.0087 (12)	−0.0101 (11)
C21	0.0274 (15)	0.0254 (13)	0.0214 (13)	−0.0014 (12)	0.0013 (11)	0.0009 (11)
C22	0.0213 (13)	0.0157 (11)	0.0203 (12)	0.0019 (10)	0.0036 (11)	−0.0016 (10)

Geometric parameters (Å, º)

O1W—H1W	0.82 (4)	C8—H8A	0.9900
O1W—H2W	0.86 (6)	C8—H8B	0.9900
N1—C4	1.334 (3)	C9—H9	1.0000
N1—C15	1.458 (3)	C11—C14	1.518 (4)
N1—H1	0.8800	C11—C13	1.521 (4)
N2—C5	1.339 (3)	C11—C12	1.523 (4)
N2—C3	1.462 (3)	C12—H12A	0.9800
N2—C9	1.477 (3)	C12—H12B	0.9800
N3—C10	1.337 (3)	C12—H12C	0.9800
N3—C6	1.453 (3)	C13—H13A	0.9800
N3—H3	0.8800	C13—H13B	0.9800
O1—C4	1.232 (3)	C13—H13C	0.9800
O2—C5	1.226 (3)	C14—H14A	0.9800
O3—C10	1.221 (3)	C14—H14B	0.9800
O4—C10	1.347 (3)	C14—H14C	0.9800
O4—C11	1.472 (3)	C15—C17	1.524 (3)
C1—C9	1.515 (3)	C15—C16	1.527 (3)
C1—C2	1.533 (4)	C15—H15	1.0000
C1—H1A	0.9900	C16—H16A	0.9800
C1—H1B	0.9900	C16—H16B	0.9800
C3—C4	1.532 (3)	C16—H16C	0.9800
C3—C2	1.546 (3)	C17—C22	1.389 (4)
C3—H3A	1.0000	C17—C18	1.400 (4)
C2—H2A	0.9900	C18—C19	1.388 (4)
C2—H2B	0.9900	C18—H18	0.9500
C5—C6	1.536 (3)	C19—C20	1.382 (4)
C6—C7	1.516 (3)	C19—H19	0.9500
C6—H6	1.0000	C20—C21	1.381 (4)
C7—C8	1.526 (4)	C20—H20	0.9500
C7—H7A	0.9900	C21—C22	1.396 (4)
C7—H7B	0.9900	C21—H21	0.9500
C8—C9	1.512 (4)	C22—H22	0.9500
H1W—O1W—H2W	107 (4)	C1—C9—H9	108.6
C4—N1—C15	124.1 (2)	O3—C10—N3	125.2 (2)
C4—N1—H1	118.0	O3—C10—O4	125.4 (2)
C15—N1—H1	118.0	N3—C10—O4	109.4 (2)
C5—N2—C3	119.8 (2)	O4—C11—C14	101.7 (2)
C5—N2—C9	127.5 (2)	O4—C11—C13	110.5 (2)
C3—N2—C9	112.48 (18)	C14—C11—C13	110.6 (2)
C10—N3—C6	121.5 (2)	O4—C11—C12	110.3 (2)
C10—N3—H3	119.2	C14—C11—C12	110.8 (2)
C6—N3—H3	119.2	C13—C11—C12	112.5 (3)
C10—O4—C11	121.6 (2)	C11—C12—H12A	109.5
C9—C1—C2	103.0 (2)	C11—C12—H12B	109.5
C9—C1—H1A	111.2	H12A—C12—H12B	109.5
C2—C1—H1A	111.2	C11—C12—H12C	109.5
C9—C1—H1B	111.2	H12A—C12—H12C	109.5
C2—C1—H1B	111.2	H12B—C12—H12C	109.5
H1A—C1—H1B	109.1	C11—C13—H13A	109.5
N2—C3—C4	109.38 (19)	C11—C13—H13B	109.5
N2—C3—C2	103.26 (19)	H13A—C13—H13B	109.5
C4—C3—C2	111.3 (2)	C11—C13—H13C	109.5
N2—C3—H3A	110.9	H13A—C13—H13C	109.5
C4—C3—H3A	110.9	H13B—C13—H13C	109.5
C2—C3—H3A	110.9	C11—C14—H14A	109.5
C1—C2—C3	103.74 (19)	C11—C14—H14B	109.5
C1—C2—H2A	111.0	H14A—C14—H14B	109.5
C3—C2—H2A	111.0	C11—C14—H14C	109.5
C1—C2—H2B	111.0	H14A—C14—H14C	109.5
C3—C2—H2B	111.0	H14B—C14—H14C	109.5
H2A—C2—H2B	109.0	N1—C15—C17	111.9 (2)
O1—C4—N1	124.7 (2)	N1—C15—C16	108.1 (2)
O1—C4—C3	121.0 (2)	C17—C15—C16	111.5 (2)
N1—C4—C3	114.2 (2)	N1—C15—H15	108.4
O2—C5—N2	121.5 (2)	C17—C15—H15	108.4
O2—C5—C6	121.5 (2)	C16—C15—H15	108.4
N2—C5—C6	117.0 (2)	C15—C16—H16A	109.5
N3—C6—C7	112.3 (2)	C15—C16—H16B	109.5
N3—C6—C5	108.26 (19)	H16A—C16—H16B	109.5
C7—C6—C5	113.5 (2)	C15—C16—H16C	109.5
N3—C6—H6	107.5	H16A—C16—H16C	109.5
C7—C6—H6	107.5	H16B—C16—H16C	109.5
C5—C6—H6	107.5	C22—C17—C18	118.6 (2)
C6—C7—C8	110.2 (2)	C22—C17—C15	122.3 (2)
C6—C7—H7A	109.6	C18—C17—C15	119.2 (2)
C8—C7—H7A	109.6	C19—C18—C17	120.7 (3)
C6—C7—H7B	109.6	C19—C18—H18	119.7
C8—C7—H7B	109.6	C17—C18—H18	119.7
H7A—C7—H7B	108.1	C20—C19—C18	120.2 (3)
C9—C8—C7	107.5 (2)	C20—C19—H19	119.9
C9—C8—H8A	110.2	C18—C19—H19	119.9
C7—C8—H8A	110.2	C21—C20—C19	119.7 (3)
C9—C8—H8B	110.2	C21—C20—H20	120.1
C7—C8—H8B	110.2	C19—C20—H20	120.1
H8A—C8—H8B	108.5	C20—C21—C22	120.4 (3)
N2—C9—C8	110.7 (2)	C20—C21—H21	119.8
N2—C9—C1	101.79 (19)	C22—C21—H21	119.8
C8—C9—C1	118.2 (2)	C17—C22—C21	120.4 (2)
N2—C9—H9	108.6	C17—C22—H22	119.8
C8—C9—H9	108.6	C21—C22—H22	119.8
C5—N2—C3—C4	−56.0 (3)	C5—N2—C9—C1	150.4 (2)
C9—N2—C3—C4	118.9 (2)	C3—N2—C9—C1	−23.9 (3)
C5—N2—C3—C2	−174.5 (2)	C7—C8—C9—N2	−51.6 (3)
C9—N2—C3—C2	0.3 (3)	C7—C8—C9—C1	−168.3 (2)
C9—C1—C2—C3	−38.2 (2)	C2—C1—C9—N2	37.4 (2)
N2—C3—C2—C1	23.4 (2)	C2—C1—C9—C8	158.8 (2)
C4—C3—C2—C1	−93.9 (2)	C6—N3—C10—O3	−2.8 (4)
C15—N1—C4—O1	2.5 (4)	C6—N3—C10—O4	177.2 (2)
C15—N1—C4—C3	179.0 (2)	C11—O4—C10—O3	−0.4 (4)
N2—C3—C4—O1	−38.8 (3)	C11—O4—C10—N3	179.6 (2)
C2—C3—C4—O1	74.7 (3)	C10—O4—C11—C14	178.8 (2)
N2—C3—C4—N1	144.5 (2)	C10—O4—C11—C13	−63.8 (3)
C2—C3—C4—N1	−102.0 (2)	C10—O4—C11—C12	61.2 (3)
C3—N2—C5—O2	−7.9 (4)	C4—N1—C15—C17	93.3 (3)
C9—N2—C5—O2	178.1 (2)	C4—N1—C15—C16	−143.5 (2)
C3—N2—C5—C6	168.2 (2)	N1—C15—C17—C22	−0.8 (3)
C9—N2—C5—C6	−5.7 (4)	C16—C15—C17—C22	−122.1 (3)
C10—N3—C6—C7	−75.2 (3)	N1—C15—C17—C18	178.6 (2)
C10—N3—C6—C5	158.7 (2)	C16—C15—C17—C18	57.4 (3)
O2—C5—C6—N3	−41.1 (3)	C22—C17—C18—C19	0.8 (4)
N2—C5—C6—N3	142.8 (2)	C15—C17—C18—C19	−178.7 (2)
O2—C5—C6—C7	−166.4 (2)	C17—C18—C19—C20	0.0 (4)
N2—C5—C6—C7	17.5 (3)	C18—C19—C20—C21	−0.7 (4)
N3—C6—C7—C8	−170.9 (2)	C19—C20—C21—C22	0.5 (4)
C5—C6—C7—C8	−47.7 (3)	C18—C17—C22—C21	−1.0 (4)
C6—C7—C8—C9	65.4 (3)	C15—C17—C22—C21	178.4 (2)
C5—N2—C9—C8	23.9 (3)	C20—C21—C22—C17	0.4 (4)
C3—N2—C9—C8	−150.4 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1W—H1W···O2	0.82 (4)	2.06 (4)	2.838 (2)	158 (3)
O1W—H2W···O1^i	0.86 (5)	2.19 (5)	2.972 (3)	151 (4)
N3—H3···O1^i	0.88	1.98	2.847 (2)	167
N1—H1···O3^i	0.88	1.93	2.807 (2)	173
C15—H15···O4^ii	1.00	2.50	3.502 (3)	175

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