Three new olanzapine structures: the acetic acid monosolvate, and the propan-2-ol and propan-2-one hemisolvate monohydrates

The crystal structures of three new solvates of olanzapine [systematic name: 2-methyl-4-(4-methyl­piperazin-1-yl)-10H-thieno[2,3-b][1,5]benzo­di­azepine], namely olanzapine acetic acid monosolvate, C₁₇H₂₀N₄S·C₂H₄O₂, (I), olanzapine propan-2-ol hemisolvate monohydrate, C₁₇H₂₀N₄S·0.5C₃H₈O·H₂O, (II), and olanzapine propan-2-one hemisolvate monohydrate, C₁₇H₂₀N₄S·0.5C₃H₆O·H₂O, (III), are presented and compared with other known olanzapine forms. There is a fairly close resemblance of the mol­ecular conformation for all studied analogues. The crystal structures are built up through olanzapine dimers, which are characterized via C-H...[pi] inter­actions between the aliphatic fragment (1-methyl­piperazin-4-yl) and the aromatic fragment (benzene system). All solvent (guest) mol­ecules participate in hydrogen-bonding networks. The crystal packing is sustained via inter­molecular N_host-H...O_guest, O_guest-H...N_host, O_guest-H...O_guest and C_host-H...O_guest hydrogen bonds. It should be noted that the solvent propan-2-ol in (II) and propan-2-one in (III) show orientational disorder. The propan-2-ol mol­ecule lies close to a twofold axis, while the propan-2-one mol­ecule resides strictly on a twofold axis through the carbonyl C atom. In both cases, the water mol­ecules present positional disorder of the H atoms.

S1. Comment

2-Methyl-4-(4-methylpiperazin-1-yl)-10H-thieno[2,3-b][1,5]benzodiazepine, commonly known as olanzapine, belongs to the class of antipsychotic drugs. It is marketed as Zyprexa by Eli Lilly and Company, and is used in the treatment of various psychoses such as psychosis, schizophrenia, schizophreniform disorders, mild anxiety states and functional bowel disorders (Tollefson et al., 1997). Olanzapine, along with, for example, clozapine and ziprasidone, can be classed as atypical antipsychotic agents of a newer generation (Tandon & Jibson, 2003; Heresco-Levy et al., 2004; Dossenbach et al., 2004), which show better efficacy and reduced side effects, less dysphoria or less impaired cognition (Tandon, 2002). According to a recent literature survey (Lindsley, 2012), olanzapine is listed in the top 20 prescription drugs. Olanzapine is known to exist in various crystalline forms which have been well documented in the literature. It is worth remembering that the propensity of pharmaceutically active substances to assume several crystal forms with different molecular arrangements can be ascribed to the complexity of their chemical structures (Borka, 1991). Based on its inner [Molecular?] structure, a pharmaceutical crystalline compound may be one of a group of polymorphs or molecular adducts if its lattice consists of many components (Haleblian, 1975). The presence of solvent in the crystal lattice confers unique physicochemical properties on the solvates (solubility and dissolution rate), which can affect the bioavailability of the drug (Armas et al., 2007). Screening for diverse crystal modifications has become more and more important for reasons of patent establishment (Bernstein, 2002; Hilfiker, 2008), and it can provide valuable knowledge necessary for further development of the drug formulation (Rustichellia et al., 2000; Singh et al., 2000; van Tonder et al., 2004; Chadha et al., 2009). For example, organic solvates, which appear in pharmacy more rarely than hydrates (Sarma & Desiraju, 1999), may have favorable formulation properties (Byrn et al., 1999). In addition, obtaining a series of isostructural solvates offers a rare possibility to study the effects of a crystal structure on solid-state properties (Nanagia & Desiraju, 1999). Solvates can play different roles, such as space fillers or principal components of the crystal lattice, through interacting with the host molecules by specific intermolecular hydrogen-bond interactions. This paper presents a study of three new crystal structures of olanzapine solvates determined by single-crystal X-ray diffraction analysis, namely olanzapine acetic acid monosolvate, (I), olanzapine propan-2-ol hemisolvate monohydrate, (II), and olanzapine propan-2-one hemisolvate monohydrate, (III).

This structural study completes a model series of olanzapine, deposited in recent years in the Cambridge Structural Database (CSD, Version 5.34; Allen, 2002). Olanzapine has been reported as polymorphs (Reutzel-Edens et al., 2003; Wawrzycka-Gorczyca et al., 2004; Thakuria & Nangia, 2011a), hydrates (Reutzel-Edens et al., 2003; Wawrzycka-Gorczyca et al., 2007), hydrated solvates, such as olanzapine methanol solvate monohydrate (Capuano et al., 2003), olanzapine dimethyl sulfoxide monohydrate (Polla et al., 2005), olanzapine ethanol solvate dihydrate, olanzapine butan-2-ol solvate monohydrate (Wawrzycka-Gorczyca et al., 2007), other solvates, such as olanzapine methanol solvate (Wawrzycka-Gorczyca et al., 2004), olanzapine dichloromethane (Wawrzycka-Gorczyca et al., 2007), and salts, such as olanzapine nicotinic acid (Ravikumar et al., 2005), olanzapine maleate and olanzapine (bis)maleate (Thakuria & Nangia, 2011b), and olanzapine benzoate (Sridhar & Ravikumar, 2007). A close examination of the lattice parameters suggests that there are three sets of isostructural crystals. A precise quantitative comparison of the structural similarity of all known forms of olanzapine, including a clarification of the nature of the intermolecular interactions, will be published elsewhere.

All the solvates reported here crystallize in monoclinic crystal systems: (I) is in the primitive P2₁/c space group, with one olanzapine and one acetic acid molecule in the asymmetric unit. Conversely, the hemisolvates (II) and (III) crystallize in the C-centred C2/c space group with one olanzapine molecule and one water molecule each, and half a propan-2-ol molecule in (II) or half a propan-2-one molecule in (III) (Figs. 1–3). The olanzapine molecule consists of three fused rings, namely benzene, diazepine and thiophene, and also a 1-methylpiperazin-4-yl fragment.

The conformation of olanzapine is rather rigid and, as expected, no noticeable difference is observed between the new solvated crystal structures and those reported previously. The 1,5-diazepine rings adopt the expected boat conformation and can be described by three planes, a bow (C2/N2/C3), a central plane (C1/C2/C3/C4) and a stern plane (C1/N1/C4/C5). The bow angle is about 112–114° for the structures presented here, while the stern angle is in the range 3–4°. The benzene and thiophene systems are planar, which enables the thienobenzodiazepine ring skeleton to form an extended V-shaped conformation. It is worth mentioning that these conformations have also been observed in related antipsychotic agents (Petcher & Weber, 1974; Cosulich & Lovell, 1977; Ravikumar et al., 2005) and they enable drug–receptor binding interactions (Ravikumar et al., 2005). The piperazine rings of (I)–(III) favour an almost perfect chair conformation, with the methyl group assuming an equatorial orientation. In all three solvates, the piperazine and benzodiazepine rings are in an anticlinal conformation (N1—C5—N3—C13 torsion angles of about 150°) towards themselves. As expected, the geometries of the molecules do not show unusual features compared with other olanzapine structures. A superimposition (on the central 1,5-diazepine ring) of all known olanzapine forms is presented in Fig. 4 in order to reveal the subtle differences in the olanzapine conformations in all the currently known olanzapine crystal structures.

In the title structures, the olanzapine molecules are arranged in a herring-bone pattern, like the majority of known olanzapine forms. Apart from that, the olanzapine molecules, identically to the previously described structures, are associated in a head-to-tail motif in centrosymmetric (inversion-related) dimers, which are characterized only by C—H···π interactions between the aliphatic 1-methylpiperazin-4-yl fragment and the aromatic benzene/thiophene system. These dimers are linked through the solvent molecules, while in the anhydrous compound, (I), the olanzapine pairs are connected by the N—H···N hydrogen bonds. [Please confirm added text]

The incorporation of solvent molecules into the crystal structures leads to many intermolecular O_guest—H···O_guest, O_guest—H···N_host, N_host—H···O_guest and C_host—H···O_guest hydrogen bonds in all three solvates. The water solvent molecule in (II) and (III) is strongly bound to the structure (being both a donor and an acceptor of strong hydrogen bonds). Hydrogen-bonding interactions are presented in Tables 1–3. In solvates (II) and (III), one of the water H atoms is disordered over two orientations. In the first orientation, it is a donor related by a symmetry centre O1W—H2AW···O1Wⁱ [symmetry codes: (i) -x + 1/2, -y + 1/2, -z in (II); (i) -x + 3/2, -y + 3/2, -z + 1 in (III)], and in the second orientation it is a propan-2-ol hydroxy-group donor (O1W—H2BW···O1) or a propan-2-one carbonyl O atom donor (O1W—H2BW···O1). In the case of (II), both hydrogen bonds have comparable bond lengths and angles within a 3σ range (Tables 2 and 3), while in (III) they cover a large range of contact distances. In the case of the acetic acid solvate, (I), the typical olanzapine dimers are hydrogen-bonded to the acetic acid molecules, indicating strong host–guest interactions, and also to other dimers via C—H···O interactions.

In (I), the olanzapine and acetic acid molecules are linked together by a strong O1—H1···N4 hydrogen bond which, combined with the N2—H2···O2ⁱ interaction [symmetry code: (i) -x + 1, y - 1/2, -z + 3/2], forms infinite zigzag chains (Fig. 5) along the crystallographic b axis, which can be described by the graph-set motif C₂²(13) in graph-set notation (Etter et al., 1990; Bernstein et al., 1995). In (II), two perpendicular chains exist: an 11-membered chain with a C₂²(11) graph-set motif, which runs along the b axis, and a C₃³(9) chain along the a axis, formed through O1W···H2—N2ⁱ, O1W—H1W···N4ⁱⁱ, O1W—H2AW···O1Wⁱⁱⁱ and O1W—H2BW···O1 hydrogen bonds [symmetry codes: (ii) -x + 1/2, y - 1/2, -z + 1/2; (iii) -x + 1/2, -y + 1/2, -z]. As a result, 13-membered rings, with an R₄⁴(13) motif, are formed along the b axis (Fig. 6). In (III), O1W—H1W···N4ⁱ and N2—H2···O1W intermolecular interactions link the host and guest molecules into parallel zigzag chains along the crystallographic b axis [symmetry codes: (i) -x + 3/2, y + 1/2, -z + 3/2 [Not the same symop as defined for (i) in (III) above - please check carefully]], which can be classified in graph-set notation as C₂²(11) (Fig. 7). A propan-2-one molecule takes part in two weak hydrogen-bond contacts, viz. O1···H2BW—O1W and C20—H20C···O1Wⁱ [symmetry code: (i) -x + 1, y, -z + 1/2 [A different definition of (i) again - please check carefully]].

To conclude, the molecular structures of three new solvate phases of olanzapine are very similar to those of the other known analogues. The presence of olanzapine dimers, which is a characteristic feature of solid-state olanzapine structures, is confirmed. Nevertheless, the architectures of all the solvates are different. The solvent molecules play a crucial role as crystal lattice stabilizers and as significant building elements in the formation of hydrogen-bond networks. The three new olanzapine solvate phases presented here reveal two types of disorder: orientational disorder of the propan-2-ol and propan-2-one solvent molecules, and positional disorder of the solvent water molecules.

Related literature

For related literature, see: Allen (2002); Armas et al. (2007); Bernstein (2002); Bernstein et al. (1995); Borka (1991); Byrn et al. (1999); Capuano et al. (2003); Chadha et al. (2009); Cosulich & Lovell (1977); Dossenbach et al. (2004); Etter et al. (1990); Haleblian (1975); Heresco-Levy, Ermilov, Lichtenberg, Bar & Javitt (2004); Hilfiker (2008); Lindsley (2012); Nanagia & Desiraju (1999); Petcher & Weber (1974); Polla et al. (2005); Ravikumar et al. (2005); Reutzel-Edens, Bush, Magee, Stephenson & Byrn (2003); Rustichellia et al. (2000); Sarma & Desiraju (1999); Singh et al. (2000); Sridhar & Ravikumar (2007); Tandon (2002); Tandon & Jibson (2003); Thakuria & Nangia (2011a, 2011b); Tollefson et al. (1997); Tonder et al. (2004); Wawrzycka-Gorczyca, Borowski, Osypiuk-Tomasik, Mazur & Kozioł (2007); Wawrzycka-Gorczyca, Koziol, Glice & Cybulski (2004).

S2. Experimental

Suitable diffraction-quality monocrystals of (I)–(III) were obtained by slow evaporation of the solvents from the corresponding solution of olanzapine [acetic acid, water–propan-2-ol (1:1 v/v) and water–propan-2-one (1:1 v/v), respectively] at room temperature. Olanzapine and the solvents were purchased from Sigma–Aldrich Inc.

S3. Refinement

H atoms, except those of the disordered solvent molecules, were located in difference Fourier maps but were treated differently in the refinements. Those bonded to C atoms were subsequently geometrically optimized and refined as riding atoms, with C—H = 0.93 Å for CH groups, 0.97 Å for secondary CH₂ groups and 0.96 Å for CH₃ groups, and with U_iso(H) = 1.2U_eq(C) for methine and methylene H atoms or 1.5U_eq(C) for methyl H atoms. H atoms bonded to N atoms were refined freely. One of the water H atoms in each of (II) and (III) is disordered over two sites (0.5:0.5). Water H atoms were restrained to have an O—H bond length of 0.82 (1) Å. The H atoms of methyl group C8 in all the olanzapine molecules, and methyl group C19 in the acetic acid solvent molecule of (I), were disordered over six sites, each with a site-occupancy factor of 0.5. The propan-2-ol solvent molecule of (II) and the propan-2-one solvent molecule of (III) both exhibit 0.5:0.5 site-occupancy disorder around a twofold axis. [Correct diffractometer given for (III)?]

Computing details

For all compounds, data collection: APEX2 (Bruker, 2005); cell refinement: SAINT-Plus (Bruker, 2008); data reduction: SAINT-Plus (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009) and Mercury (Macrae et al., 2008); software used to prepare material for publication: PLATON (Spek, 2009).

Figures

	Fig. 1. A perspective view of (I), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. The dashed line indicates the hydrogen bond.
	Fig. 2. A perspective view of (II), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. Dashed lines indicate hydrogen bonds.
	Fig. 3. A perspective view of (III), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. Dashed lines indicate hydrogen bonds.
	Fig. 4. Overlay plot of all currently known olanzapine crystal structures, superimposed on their common central 1,5-diazepine ring. In the electronic version of the paper, polymorphs are shown in black, solvates in blue [Pale green?] and salts in red.
	Fig. 5. A partial packing diagram for (I). Intermolecular hydrogen bonds are indicated by dashed lines. H atoms not involved in the hydrogen bonds have been omitted for clarity. [Symmetry code: (i) -x + 1, y - 1/2, -z + 3/2.]
	Fig. 6. A partial packing diagram for (II). Intermolecular hydrogen bonds are indicated by dashed lines. H atoms not involved in the hydrogen bonds have been omitted for clarity. [Symmetry codes: (i) x, -y + 1, z - 1/2; (ii) -x + 1/2, -y + 1/2, -z; (iii) -x + 1/2, y - 1/2, -z + 1/2.]
	Fig. 7. A partial packing diagram for (III). Intermolecular hydrogen bonds are indicated by dashed lines. H atoms not involved in the hydrogen bonds have been omitted for clarity. [Symmetry codes: (i) -x + 3/2, -y + 3/2, -z + 1; (ii) -x + 3/2, y + 1/2, -z + 3/2; (iii) -x + 1, y, -z + 1/2.]

(I) 2-Methyl-4-(4-methylpiperazin-1-yl)-10H-thieno[2,3-b][1,5]benzodiazepine acetic acid monosolvate

Crystal data

C17H20N4S·C2H4O2	F(000) = 792
Mr = 372.49	Dx = 1.305 Mg m^−3
Monoclinic, P21/c	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2ybc	Cell parameters from 9926 reflections
a = 10.1474 (1) Å	θ = 4.4–65.9°
b = 12.8562 (1) Å	µ = 1.69 mm^−1
c = 14.5494 (1) Å	T = 296 K
β = 92.92°	Plate, yellow
V = 1895.61 (3) Å^3	0.20 × 0.15 × 0.10 mm
Z = 4

Data collection

Bruker SMART APEXII CCD area-detector diffractometer	3298 independent reflections
Radiation source: 30W microsource with MonoCap capillary	3201 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.020
ω scans	θmax = 66.4°, θmin = 4.4°
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)	h = −12→11
Tmin = 0.729, Tmax = 0.849	k = −14→15
22793 measured reflections	l = −16→17

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)] = 0.033	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.094	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	w = 1/[σ^2(Fo^2) + (0.0508P)^2 + 0.522P] where P = (Fo^2 + 2Fc^2)/3
3298 reflections	(Δ/σ)max < 0.001
246 parameters	Δρmax = 0.27 e Å^−3
8 restraints	Δρmin = −0.16 e Å^−3

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement on F² for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The observed criterion of F² > σ(F²) is used only for calculating -R-factor-obs etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
S1	0.45237 (4)	−0.07053 (3)	0.79115 (2)	0.0446 (1)
N1	0.65019 (11)	0.15984 (9)	0.58964 (8)	0.0402 (3)
N2	0.64466 (13)	0.07813 (10)	0.77878 (8)	0.0424 (4)
N3	0.43690 (11)	0.18777 (10)	0.53895 (8)	0.0427 (4)
N4	0.25039 (12)	0.26759 (9)	0.40282 (8)	0.0413 (4)
C1	0.75508 (13)	0.10578 (11)	0.63476 (10)	0.0378 (4)
C2	0.75906 (14)	0.07071 (10)	0.72642 (10)	0.0390 (4)
C3	0.53228 (13)	0.03049 (11)	0.73826 (9)	0.0374 (4)
C4	0.47610 (13)	0.05178 (11)	0.65303 (9)	0.0359 (4)
C5	0.52763 (13)	0.13579 (10)	0.59543 (9)	0.0359 (4)
C6	0.36849 (13)	−0.01695 (11)	0.62963 (10)	0.0384 (4)
C7	0.34205 (14)	−0.08577 (11)	0.69670 (10)	0.0419 (4)
C8	0.23938 (16)	−0.16921 (13)	0.69635 (13)	0.0554 (6)
C9	0.87637 (15)	0.03289 (12)	0.76707 (11)	0.0475 (5)
C10	0.98955 (15)	0.02677 (13)	0.71845 (12)	0.0527 (5)
C11	0.98592 (15)	0.05653 (13)	0.62757 (12)	0.0509 (5)
C12	0.87048 (14)	0.09684 (12)	0.58710 (11)	0.0450 (4)
C13	0.30222 (14)	0.21050 (12)	0.56269 (10)	0.0409 (4)
C14	0.21039 (14)	0.19900 (12)	0.47803 (11)	0.0454 (5)
C15	0.39011 (16)	0.24938 (13)	0.38412 (10)	0.0476 (5)
C16	0.48019 (14)	0.26012 (13)	0.46909 (10)	0.0473 (5)
C17	0.1655 (2)	0.24862 (15)	0.31893 (12)	0.0624 (6)
O1	0.17092 (13)	0.45622 (9)	0.41745 (9)	0.0610 (4)
O2	0.30001 (15)	0.49414 (12)	0.53834 (9)	0.0764 (5)
C18	0.21494 (16)	0.51836 (12)	0.48081 (10)	0.0470 (5)
C19	0.1540 (2)	0.62456 (15)	0.47671 (14)	0.0681 (7)
H2	0.6601 (17)	0.0574 (14)	0.8346 (13)	0.052 (5)*
H6	0.32090	−0.01450	0.57330	0.0460*
H8A	0.24510	−0.20530	0.75420	0.0830*	0.500
H8B	0.25370	−0.21740	0.64740	0.0830*	0.500
H8C	0.15350	−0.13850	0.68720	0.0830*	0.500
H8D	0.18980	−0.16880	0.63840	0.0830*	0.500
H8E	0.18110	−0.15680	0.74510	0.0830*	0.500
H8F	0.28140	−0.23560	0.70530	0.0830*	0.500
H9	0.87870	0.01130	0.82810	0.0570*
H10	1.06780	0.00270	0.74700	0.058 (5)*
H11	1.06050	0.04960	0.59350	0.058 (5)*
H12	0.86980	0.11870	0.52610	0.0540*
H13A	0.29720	0.28090	0.58630	0.0490*
H13B	0.27590	0.16300	0.61020	0.0490*
H14A	0.21100	0.12730	0.45740	0.0540*
H14B	0.12110	0.21620	0.49360	0.0540*
H15A	0.41670	0.29870	0.33820	0.0570*
H15B	0.39930	0.18000	0.35900	0.0570*
H16A	0.57030	0.24460	0.45450	0.0570*
H16B	0.47730	0.33090	0.49210	0.0570*
H17A	0.17510	0.17770	0.29970	0.0930*
H17B	0.19110	0.29430	0.27080	0.0930*
H17C	0.07510	0.26150	0.33180	0.0930*
H1	0.204 (2)	0.3982 (8)	0.4204 (17)	0.0910*
H19A	0.08920	0.62770	0.42640	0.1020*	0.63 (3)
H19B	0.22130	0.67560	0.46790	0.1020*	0.63 (3)
H19C	0.11250	0.63840	0.53330	0.1020*	0.63 (3)
H19D	0.19280	0.66680	0.52530	0.1020*	0.37 (3)
H19E	0.06070	0.61890	0.48380	0.1020*	0.37 (3)
H19F	0.16950	0.65600	0.41840	0.1020*	0.37 (3)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0512 (2)	0.0453 (2)	0.0377 (2)	0.0055 (2)	0.0075 (2)	0.0103 (1)
N1	0.0376 (6)	0.0391 (6)	0.0434 (6)	−0.0003 (5)	−0.0015 (5)	0.0065 (5)
N2	0.0483 (7)	0.0473 (7)	0.0311 (6)	0.0033 (5)	−0.0033 (5)	−0.0021 (5)
N3	0.0350 (6)	0.0503 (7)	0.0429 (6)	0.0034 (5)	0.0038 (5)	0.0170 (5)
N4	0.0456 (7)	0.0389 (7)	0.0387 (6)	0.0042 (5)	−0.0042 (5)	0.0038 (5)
C1	0.0371 (7)	0.0328 (7)	0.0430 (7)	−0.0014 (5)	−0.0036 (5)	−0.0022 (6)
C2	0.0418 (7)	0.0344 (7)	0.0400 (7)	0.0018 (5)	−0.0048 (6)	−0.0069 (5)
C3	0.0422 (7)	0.0358 (7)	0.0345 (7)	0.0069 (6)	0.0042 (5)	0.0007 (5)
C4	0.0365 (7)	0.0361 (7)	0.0350 (7)	0.0033 (5)	0.0015 (5)	0.0026 (5)
C5	0.0384 (7)	0.0353 (7)	0.0340 (6)	0.0017 (5)	0.0006 (5)	0.0013 (5)
C6	0.0378 (7)	0.0377 (7)	0.0396 (7)	0.0028 (5)	0.0008 (5)	0.0033 (6)
C7	0.0413 (7)	0.0369 (7)	0.0479 (8)	0.0046 (6)	0.0078 (6)	0.0044 (6)
C8	0.0530 (9)	0.0440 (9)	0.0700 (11)	−0.0039 (7)	0.0105 (8)	0.0105 (8)
C9	0.0522 (8)	0.0461 (8)	0.0428 (8)	0.0077 (7)	−0.0113 (6)	−0.0054 (6)
C10	0.0423 (8)	0.0504 (9)	0.0637 (10)	0.0087 (7)	−0.0136 (7)	−0.0093 (7)
C11	0.0366 (8)	0.0520 (9)	0.0638 (10)	−0.0007 (6)	0.0007 (7)	−0.0063 (7)
C12	0.0401 (7)	0.0468 (8)	0.0478 (8)	−0.0047 (6)	−0.0001 (6)	0.0002 (6)
C13	0.0396 (7)	0.0420 (8)	0.0417 (7)	0.0053 (6)	0.0069 (6)	0.0084 (6)
C14	0.0390 (7)	0.0432 (8)	0.0538 (9)	0.0010 (6)	0.0002 (6)	0.0099 (6)
C15	0.0537 (9)	0.0488 (9)	0.0409 (7)	0.0083 (7)	0.0085 (6)	0.0117 (6)
C16	0.0393 (7)	0.0527 (9)	0.0502 (8)	0.0001 (6)	0.0050 (6)	0.0196 (7)
C17	0.0750 (12)	0.0569 (10)	0.0528 (9)	0.0024 (9)	−0.0202 (8)	−0.0045 (8)
O1	0.0730 (8)	0.0457 (6)	0.0615 (7)	0.0094 (6)	−0.0226 (6)	−0.0098 (6)
O2	0.0933 (10)	0.0778 (9)	0.0550 (7)	0.0177 (8)	−0.0264 (7)	−0.0188 (6)
C18	0.0538 (9)	0.0491 (9)	0.0382 (8)	−0.0022 (7)	0.0028 (6)	−0.0020 (6)
C19	0.0845 (13)	0.0472 (10)	0.0725 (12)	0.0051 (9)	0.0036 (10)	−0.0066 (8)

Geometric parameters (Å, º)

S1—C3	1.7320 (14)	C6—H6	0.9300
S1—C7	1.7388 (15)	C8—H8B	0.9600
O1—C18	1.283 (2)	C8—H8E	0.9600
O2—C18	1.212 (2)	C8—H8F	0.9600
O1—H1	0.818 (13)	C8—H8D	0.9600
N1—C5	1.2884 (17)	C8—H8A	0.9600
N1—C1	1.4056 (18)	C8—H8C	0.9600
N2—C3	1.3981 (19)	C9—H9	0.9300
N2—C2	1.4238 (19)	C10—H10	0.9300
N3—C13	1.4562 (18)	C11—H11	0.9300
N3—C16	1.462 (2)	C12—H12	0.9300
N3—C5	1.3757 (18)	C13—H13B	0.9700
N4—C14	1.478 (2)	C13—H13A	0.9700
N4—C17	1.478 (2)	C14—H14B	0.9700
N4—C15	1.476 (2)	C14—H14A	0.9700
N2—H2	0.862 (19)	C15—H15B	0.9700
C1—C2	1.406 (2)	C15—H15A	0.9700
C1—C12	1.396 (2)	C16—H16A	0.9700
C2—C9	1.390 (2)	C16—H16B	0.9700
C3—C4	1.3659 (19)	C17—H17C	0.9600
C4—C5	1.4788 (19)	C17—H17B	0.9600
C4—C6	1.4322 (19)	C17—H17A	0.9600
C6—C7	1.354 (2)	C18—C19	1.499 (2)
C7—C8	1.495 (2)	C19—H19A	0.9600
C9—C10	1.381 (2)	C19—H19B	0.9600
C10—C11	1.375 (2)	C19—H19C	0.9600
C11—C12	1.385 (2)	C19—H19D	0.9600
C13—C14	1.513 (2)	C19—H19E	0.9600
C15—C16	1.506 (2)	C19—H19F	0.9600
C3—S1—C7	91.75 (7)	H8C—C8—H8E	56.00
C18—O1—H1	113.8 (16)	H8C—C8—H8F	141.00
C1—N1—C5	124.15 (12)	H8D—C8—H8E	109.00
C2—N2—C3	114.51 (11)	H8D—C8—H8F	109.00
C5—N3—C13	124.29 (12)	H8E—C8—H8F	109.00
C13—N3—C16	110.86 (11)	H8B—C8—H8D	56.00
C5—N3—C16	120.58 (11)	C10—C9—H9	119.00
C14—N4—C17	110.03 (12)	C2—C9—H9	119.00
C15—N4—C17	110.28 (12)	C9—C10—H10	120.00
C14—N4—C15	110.15 (11)	C11—C10—H10	120.00
C3—N2—H2	111.6 (12)	C10—C11—H11	120.00
C2—N2—H2	111.7 (12)	C12—C11—H11	120.00
N1—C1—C2	125.87 (12)	C11—C12—H12	119.00
N1—C1—C12	116.31 (13)	C1—C12—H12	119.00
C2—C1—C12	117.41 (13)	N3—C13—H13B	110.00
N2—C2—C1	120.07 (12)	C14—C13—H13A	110.00
N2—C2—C9	119.99 (13)	C14—C13—H13B	110.00
C1—C2—C9	119.89 (13)	H13A—C13—H13B	108.00
S1—C3—C4	111.74 (10)	N3—C13—H13A	110.00
S1—C3—N2	122.10 (10)	N4—C14—H14A	109.00
N2—C3—C4	126.07 (13)	N4—C14—H14B	109.00
C3—C4—C5	121.17 (12)	C13—C14—H14B	109.00
C3—C4—C6	111.72 (12)	H14A—C14—H14B	108.00
C5—C4—C6	127.10 (12)	C13—C14—H14A	109.00
N3—C5—C4	116.62 (11)	N4—C15—H15A	109.00
N1—C5—C4	125.64 (12)	C16—C15—H15A	109.00
N1—C5—N3	117.60 (12)	C16—C15—H15B	109.00
C4—C6—C7	114.11 (13)	N4—C15—H15B	109.00
S1—C7—C6	110.65 (11)	H15A—C15—H15B	108.00
S1—C7—C8	120.26 (11)	N3—C16—H16B	110.00
C6—C7—C8	129.04 (14)	C15—C16—H16A	110.00
C2—C9—C10	121.23 (15)	C15—C16—H16B	110.00
C9—C10—C11	119.62 (15)	H16A—C16—H16B	108.00
C10—C11—C12	119.58 (15)	N3—C16—H16A	110.00
C1—C12—C11	122.18 (15)	N4—C17—H17A	110.00
N3—C13—C14	109.50 (12)	N4—C17—H17B	109.00
N4—C14—C13	111.30 (12)	H17A—C17—H17B	109.00
N3—C16—C15	108.73 (12)	H17A—C17—H17C	109.00
C7—C6—H6	123.00	H17B—C17—H17C	109.00
C4—C6—H6	123.00	N4—C17—H17C	109.00
C7—C8—H8A	109.00	O1—C18—C19	114.26 (14)
C7—C8—H8B	109.00	O2—C18—C19	122.64 (15)
C7—C8—H8D	109.00	O1—C18—O2	123.09 (15)
C7—C8—H8E	109.00	C18—C19—H19A	110.00
C7—C8—H8C	109.00	C18—C19—H19B	109.00
H8A—C8—H8B	109.00	C18—C19—H19C	109.00
H8A—C8—H8C	110.00	C18—C19—H19D	109.00
H8A—C8—H8D	141.00	C18—C19—H19E	109.00
H8A—C8—H8E	56.00	C18—C19—H19F	109.00
H8A—C8—H8F	56.00	H19A—C19—H19B	109.00
H8B—C8—H8C	109.00	H19A—C19—H19C	109.00
C7—C8—H8F	109.00	H19B—C19—H19C	109.00
H8B—C8—H8E	141.00	H19D—C19—H19E	109.00
H8B—C8—H8F	56.00	H19D—C19—H19F	109.00
H8C—C8—H8D	56.00	H19E—C19—H19F	109.00
C3—S1—C7—C6	0.52 (12)	C12—C1—C2—C9	2.5 (2)
C3—S1—C7—C8	178.39 (13)	N1—C1—C12—C11	172.22 (14)
C7—S1—C3—N2	−176.25 (12)	C12—C1—C2—N2	179.75 (13)
C7—S1—C3—C4	0.57 (11)	N1—C1—C2—C9	−169.84 (13)
C5—N1—C1—C12	144.11 (14)	N1—C1—C2—N2	7.4 (2)
C1—N1—C5—N3	−172.39 (12)	C1—C2—C9—C10	−1.4 (2)
C5—N1—C1—C2	−43.5 (2)	N2—C2—C9—C10	−178.70 (14)
C1—N1—C5—C4	3.1 (2)	N2—C3—C4—C5	−3.8 (2)
C3—N2—C2—C9	−127.65 (14)	S1—C3—C4—C6	−1.47 (15)
C2—N2—C3—C4	−56.81 (19)	N2—C3—C4—C6	175.20 (13)
C2—N2—C3—S1	119.54 (12)	S1—C3—C4—C5	179.56 (10)
C3—N2—C2—C1	55.09 (17)	C6—C4—C5—N1	−141.58 (15)
C13—N3—C16—C15	−60.26 (16)	C6—C4—C5—N3	33.9 (2)
C16—N3—C13—C14	60.91 (15)	C3—C4—C5—N3	−147.26 (13)
C13—N3—C5—N1	−148.91 (13)	C3—C4—C6—C7	1.93 (18)
C16—N3—C5—C4	−170.14 (12)	C5—C4—C6—C7	−179.17 (13)
C5—N3—C16—C15	141.97 (13)	C3—C4—C5—N1	37.2 (2)
C5—N3—C13—C14	−142.31 (13)	C4—C6—C7—C8	−179.09 (14)
C16—N3—C5—N1	5.75 (19)	C4—C6—C7—S1	−1.47 (16)
C13—N3—C5—C4	35.20 (19)	C2—C9—C10—C11	−1.4 (2)
C15—N4—C14—C13	53.76 (15)	C9—C10—C11—C12	3.0 (2)
C14—N4—C15—C16	−54.25 (16)	C10—C11—C12—C1	−1.9 (2)
C17—N4—C15—C16	−175.88 (13)	N3—C13—C14—N4	−57.37 (16)
C17—N4—C14—C13	175.54 (13)	N4—C15—C16—N3	57.06 (17)
C2—C1—C12—C11	−0.8 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···N4	0.82 (1)	1.77 (1)	2.5679 (17)	166 (2)
N2—H2···O2^i	0.862 (19)	2.041 (19)	2.8998 (18)	174.4 (17)
C8—H8F···N2^i	0.96	2.52	3.468 (2)	171

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

(II) 2-Methyl-4-(4-methylpiperazin-1-yl)-10H-thieno[2,3-b][1,5]benzodiazepine propan-2-ol hemisolvate monohydrate

Crystal data

C17H20N4S·0.5C3H8O·H2O	F(000) = 1544
Mr = 360.51	Dx = 1.249 Mg m^−3
Monoclinic, C2/c	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: -C 2yc	Cell parameters from 9708 reflections
a = 24.5414 (4) Å	θ = 2.8–67.0°
b = 12.5088 (3) Å	µ = 1.63 mm^−1
c = 15.3096 (4) Å	T = 296 K
β = 125.314 (1)°	Prism, yellow
V = 3835.01 (16) Å^3	0.40 × 0.25 × 0.20 mm
Z = 8

Data collection

Bruker SMART APEXII CCD area-detector diffractometer	3385 independent reflections
Radiation source: 30W microsource with MonoCap capillary	3341 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.021
ω scans	θmax = 67.0°, θmin = 4.2°
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)	h = −29→29
Tmin = 0.63, Tmax = 0.74	k = −14→14
23622 measured reflections	l = −17→18

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)] = 0.035	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.100	w = 1/[σ^2(Fo^2) + (0.0574P)^2 + 1.6621P] where P = (Fo^2 + 2Fc^2)/3
S = 1.04	(Δ/σ)max < 0.001
3385 reflections	Δρmax = 0.19 e Å^−3
264 parameters	Δρmin = −0.18 e Å^−3
5 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^* = kFc[1+0.001Fc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.00175 (13)

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement on F² for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The observed criterion of F² > σ(F²) is used only for calculating -R-factor-obs etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
S1	0.29248 (2)	0.15475 (3)	0.24465 (3)	0.0562 (2)
N1	0.16736 (5)	0.37335 (9)	0.31448 (9)	0.0433 (3)
N2	0.18683 (6)	0.29524 (10)	0.15343 (10)	0.0498 (4)
N3	0.27114 (5)	0.41962 (8)	0.46204 (9)	0.0427 (3)
N4	0.35058 (6)	0.54962 (9)	0.64855 (9)	0.0516 (4)
C1	0.12178 (6)	0.30669 (10)	0.22787 (10)	0.0415 (4)
C2	0.12802 (6)	0.27120 (11)	0.14713 (10)	0.0449 (4)
C3	0.24439 (6)	0.25447 (11)	0.24650 (11)	0.0436 (4)
C4	0.26632 (6)	0.28005 (10)	0.34846 (10)	0.0408 (4)
C5	0.23144 (6)	0.36005 (9)	0.37018 (10)	0.0391 (4)
C6	0.32309 (6)	0.21755 (10)	0.42610 (11)	0.0456 (4)
C7	0.34344 (7)	0.14723 (11)	0.38342 (13)	0.0525 (4)
C8	0.39945 (9)	0.06788 (15)	0.43890 (17)	0.0761 (6)
C9	0.07649 (7)	0.21363 (13)	0.06055 (12)	0.0565 (5)
C10	0.01868 (7)	0.19057 (14)	0.05237 (13)	0.0648 (5)
C11	0.01205 (7)	0.22423 (13)	0.13151 (13)	0.0589 (5)
C12	0.06272 (6)	0.28217 (11)	0.21718 (12)	0.0493 (4)
C13	0.33583 (6)	0.46104 (11)	0.49335 (11)	0.0455 (4)
C14	0.38135 (7)	0.47709 (11)	0.61347 (12)	0.0531 (4)
C15	0.28651 (8)	0.50498 (12)	0.61717 (12)	0.0541 (5)
C16	0.23996 (7)	0.48954 (11)	0.49777 (11)	0.0467 (4)
C17	0.39478 (10)	0.56624 (17)	0.76489 (13)	0.0824 (7)
O1	0.09446 (11)	0.4207 (2)	−0.1806 (3)	0.0896 (10)	0.500
C18	0.02263 (12)	0.4235 (4)	−0.2581 (4)	0.0852 (18)	0.500
C19	0.0052 (4)	0.3084 (5)	−0.2976 (7)	0.186 (4)	0.500
C20	−0.0074 (7)	0.4381 (11)	−0.1952 (9)	0.252 (8)	0.500
O1W	0.17970 (6)	0.24588 (9)	−0.03978 (10)	0.0603 (4)
H2	0.1835 (8)	0.2743 (13)	0.0950 (15)	0.056 (4)*
H6	0.34410	0.22470	0.49940	0.0550*
H8A	0.40140	0.02920	0.38670	0.1140*	0.500
H8B	0.39190	0.01880	0.47910	0.1140*	0.500
H8C	0.44090	0.10480	0.48650	0.1140*	0.500
H8D	0.42140	0.07270	0.51480	0.1140*	0.500
H8E	0.43090	0.08310	0.42240	0.1140*	0.500
H8F	0.38190	−0.00290	0.41500	0.1140*	0.500
H9	0.08110	0.19030	0.00740	0.0680*
H10	−0.01560	0.15260	−0.00620	0.0780*
H11	−0.02640	0.20800	0.12720	0.0710*
H12	0.05730	0.30560	0.26940	0.0590*
H13A	0.32960	0.52860	0.45750	0.0550*
H13B	0.35620	0.41110	0.47170	0.0550*
H14A	0.39020	0.40870	0.64910	0.0640*
H14B	0.42360	0.50660	0.63320	0.0640*
H15A	0.26600	0.55270	0.64020	0.0650*
H15B	0.29400	0.43680	0.65260	0.0650*
H16A	0.19840	0.45810	0.47930	0.0560*
H16B	0.22990	0.55820	0.46210	0.0560*
H17A	0.37430	0.61550	0.78580	0.1240*
H17B	0.43670	0.59480	0.78410	0.1240*
H17C	0.40230	0.49920	0.80080	0.1240*
H1	0.11010	0.47990	−0.17670	0.1080*	0.500
H18	0.00730	0.47620	−0.31520	0.1280*	0.500
H19A	0.03970	0.27900	−0.30190	0.2800*	0.500
H19B	−0.03650	0.30690	−0.36710	0.2800*	0.500
H19C	0.00150	0.26680	−0.24850	0.2800*	0.500
H20A	0.00020	0.51000	−0.16860	0.3770*	0.500
H20B	0.01330	0.38900	−0.13610	0.3770*	0.500
H20C	−0.05450	0.42450	−0.24110	0.3770*	0.500
H2AW	0.22061 (16)	0.247 (5)	−0.004 (4)	0.1270*	0.500
H1W	0.1672 (11)	0.1840 (19)	−0.0775 (18)	0.085 (6)*
H2BW	0.156 (2)	0.291 (4)	−0.085 (4)	0.1270*	0.500

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0518 (2)	0.0613 (3)	0.0584 (3)	−0.0023 (2)	0.0336 (2)	−0.0165 (2)
N1	0.0373 (5)	0.0427 (6)	0.0443 (6)	−0.0011 (4)	0.0204 (5)	−0.0021 (4)
N2	0.0483 (6)	0.0599 (7)	0.0403 (6)	−0.0044 (5)	0.0251 (5)	−0.0001 (5)
N3	0.0395 (5)	0.0395 (5)	0.0472 (6)	−0.0054 (4)	0.0239 (5)	−0.0100 (4)
N4	0.0558 (7)	0.0399 (6)	0.0382 (6)	0.0039 (5)	0.0151 (5)	−0.0043 (4)
C1	0.0359 (6)	0.0382 (6)	0.0409 (7)	0.0012 (5)	0.0167 (5)	0.0038 (5)
C2	0.0403 (7)	0.0441 (7)	0.0401 (7)	0.0005 (5)	0.0173 (6)	0.0044 (5)
C3	0.0408 (7)	0.0446 (7)	0.0458 (7)	−0.0068 (5)	0.0252 (6)	−0.0057 (5)
C4	0.0364 (6)	0.0374 (6)	0.0431 (7)	−0.0058 (5)	0.0198 (5)	−0.0063 (5)
C5	0.0400 (6)	0.0345 (6)	0.0407 (7)	−0.0037 (5)	0.0221 (5)	−0.0015 (5)
C6	0.0392 (7)	0.0409 (7)	0.0460 (7)	−0.0043 (5)	0.0184 (6)	−0.0080 (5)
C7	0.0418 (7)	0.0462 (7)	0.0598 (9)	−0.0022 (5)	0.0238 (7)	−0.0098 (6)
C8	0.0578 (9)	0.0629 (10)	0.0878 (13)	0.0129 (8)	0.0307 (9)	−0.0127 (9)
C9	0.0477 (8)	0.0631 (9)	0.0417 (7)	−0.0007 (6)	0.0160 (6)	−0.0049 (6)
C10	0.0407 (8)	0.0707 (10)	0.0531 (9)	−0.0081 (7)	0.0099 (7)	−0.0101 (7)
C11	0.0344 (7)	0.0662 (9)	0.0610 (9)	−0.0041 (6)	0.0188 (7)	0.0007 (7)
C12	0.0372 (7)	0.0523 (8)	0.0504 (8)	0.0024 (5)	0.0208 (6)	0.0035 (6)
C13	0.0397 (7)	0.0412 (7)	0.0502 (7)	−0.0064 (5)	0.0229 (6)	−0.0088 (5)
C14	0.0443 (7)	0.0433 (7)	0.0509 (8)	0.0029 (6)	0.0156 (6)	−0.0045 (6)
C15	0.0697 (9)	0.0425 (7)	0.0532 (8)	0.0050 (6)	0.0374 (8)	−0.0019 (6)
C16	0.0476 (7)	0.0400 (7)	0.0531 (8)	0.0003 (5)	0.0295 (6)	−0.0056 (6)
C17	0.0872 (13)	0.0775 (12)	0.0414 (9)	0.0141 (10)	0.0135 (8)	−0.0089 (8)
O1	0.0529 (13)	0.0697 (16)	0.106 (2)	0.0034 (11)	0.0227 (14)	0.0286 (15)
C18	0.053 (2)	0.105 (4)	0.082 (3)	−0.007 (2)	0.030 (2)	0.009 (3)
C19	0.110 (5)	0.209 (8)	0.197 (9)	−0.050 (6)	0.064 (6)	−0.132 (8)
C20	0.227 (11)	0.274 (14)	0.269 (17)	0.075 (13)	0.151 (11)	−0.061 (13)
O1W	0.0735 (7)	0.0471 (6)	0.0731 (8)	−0.0033 (5)	0.0497 (7)	−0.0040 (5)

Geometric parameters (Å, º)

S1—C3	1.7286 (16)	C6—H6	0.9300
S1—C7	1.7363 (17)	C8—H8E	0.9600
O1—C18	1.449 (6)	C8—H8F	0.9600
O1—H1	0.8200	C8—H8B	0.9600
O1W—H2AW	0.82 (4)	C8—H8C	0.9600
O1W—H1W	0.91 (2)	C8—H8A	0.9600
O1W—H2BW	0.82 (5)	C8—H8D	0.9600
N1—C5	1.295 (2)	C9—H9	0.9300
N1—C1	1.4107 (17)	C10—H10	0.9300
N2—C2	1.422 (2)	C11—H11	0.9300
N2—C3	1.400 (2)	C12—H12	0.9300
N3—C16	1.461 (2)	C13—H13B	0.9700
N3—C13	1.463 (2)	C13—H13A	0.9700
N3—C5	1.3778 (16)	C14—H14B	0.9700
N4—C14	1.467 (2)	C14—H14A	0.9700
N4—C17	1.469 (2)	C15—H15B	0.9700
N4—C15	1.463 (3)	C15—H15A	0.9700
N2—H2	0.89 (2)	C16—H16A	0.9700
C1—C2	1.403 (2)	C16—H16B	0.9700
C1—C12	1.396 (2)	C17—H17C	0.9600
C2—C9	1.392 (2)	C17—H17A	0.9600
C3—C4	1.3629 (19)	C17—H17B	0.9600
C4—C6	1.432 (2)	C18—C19	1.524 (8)
C4—C5	1.474 (2)	C18—C20	1.525 (18)
C6—C7	1.352 (2)	C18—H18	0.9800
C7—C8	1.499 (3)	C19—H19C	0.9600
C9—C10	1.381 (3)	C19—H19A	0.9600
C10—C11	1.378 (3)	C19—H19B	0.9600
C11—C12	1.381 (2)	C20—H20A	0.9600
C13—C14	1.515 (2)	C20—H20B	0.9600
C15—C16	1.507 (2)	C20—H20C	0.9600
C3—S1—C7	91.99 (8)	H8D—C8—H8F	109.00
C18—O1—H1	110.00	H8A—C8—H8B	109.00
H2AW—O1W—H1W	106 (5)	H8B—C8—H8C	109.00
H2AW—O1W—H2BW	123 (6)	H8B—C8—H8D	56.00
H1W—O1W—H2BW	104 (4)	H8B—C8—H8E	141.00
C1—N1—C5	122.97 (13)	H8E—C8—H8F	110.00
C2—N2—C3	112.31 (13)	C2—C9—H9	119.00
C5—N3—C13	121.29 (13)	C10—C9—H9	120.00
C5—N3—C16	119.45 (13)	C11—C10—H10	120.00
C13—N3—C16	111.69 (11)	C9—C10—H10	120.00
C14—N4—C17	110.85 (15)	C10—C11—H11	120.00
C15—N4—C17	110.62 (15)	C12—C11—H11	120.00
C14—N4—C15	109.07 (12)	C1—C12—H12	119.00
C2—N2—H2	111.7 (14)	C11—C12—H12	119.00
C3—N2—H2	111.6 (13)	C14—C13—H13B	110.00
C2—C1—C12	117.53 (13)	C14—C13—H13A	110.00
N1—C1—C12	116.47 (13)	N3—C13—H13B	110.00
N1—C1—C2	125.75 (15)	H13A—C13—H13B	108.00
N2—C2—C9	120.13 (14)	N3—C13—H13A	110.00
N2—C2—C1	119.80 (12)	N4—C14—H14A	110.00
C1—C2—C9	120.07 (16)	H14A—C14—H14B	108.00
N2—C3—C4	125.34 (15)	C13—C14—H14A	110.00
S1—C3—C4	111.52 (11)	N4—C14—H14B	110.00
S1—C3—N2	122.90 (11)	C13—C14—H14B	110.00
C3—C4—C5	121.42 (13)	N4—C15—H15B	109.00
C5—C4—C6	126.62 (12)	C16—C15—H15A	109.00
C3—C4—C6	111.91 (13)	N4—C15—H15A	109.00
N1—C5—C4	125.52 (12)	H15A—C15—H15B	108.00
N1—C5—N3	118.40 (13)	C16—C15—H15B	109.00
N3—C5—C4	115.92 (13)	C15—C16—H16B	110.00
C4—C6—C7	114.08 (13)	C15—C16—H16A	110.00
C6—C7—C8	129.13 (16)	N3—C16—H16A	110.00
S1—C7—C8	120.35 (13)	H16A—C16—H16B	108.00
S1—C7—C6	110.49 (12)	N3—C16—H16B	110.00
C2—C9—C10	120.99 (16)	N4—C17—H17A	109.00
C9—C10—C11	119.59 (16)	N4—C17—H17B	109.00
C10—C11—C12	119.75 (18)	N4—C17—H17C	109.00
C1—C12—C11	122.06 (15)	H17A—C17—H17B	110.00
N3—C13—C14	110.11 (13)	H17A—C17—H17C	110.00
N4—C14—C13	110.61 (13)	H17B—C17—H17C	109.00
N4—C15—C16	111.38 (15)	O1—C18—C20	106.8 (6)
N3—C16—C15	109.71 (14)	C19—C18—C20	103.7 (7)
C7—C6—H6	123.00	O1—C18—C19	103.4 (5)
C4—C6—H6	123.00	C20—C18—H18	114.00
C7—C8—H8A	109.00	O1—C18—H18	114.00
C7—C8—H8C	109.00	C19—C18—H18	114.00
C7—C8—H8D	109.00	C18—C19—H19B	109.00
C7—C8—H8B	109.00	H19A—C19—H19C	109.00
H8A—C8—H8D	141.00	C18—C19—H19C	109.00
H8A—C8—H8E	56.00	H19A—C19—H19B	110.00
H8A—C8—H8C	110.00	C18—C19—H19A	109.00
C7—C8—H8E	109.00	H19B—C19—H19C	110.00
C7—C8—H8F	109.00	C18—C20—H20C	110.00
H8A—C8—H8F	56.00	H20A—C20—H20C	109.00
H8B—C8—H8F	56.00	H20B—C20—H20C	110.00
H8C—C8—H8D	56.00	H20A—C20—H20B	109.00
H8C—C8—H8E	56.00	C18—C20—H20A	110.00
H8C—C8—H8F	141.00	C18—C20—H20B	109.00
H8D—C8—H8E	109.00
C3—S1—C7—C6	0.43 (14)	C12—C1—C2—C9	−0.1 (2)
C3—S1—C7—C8	178.70 (16)	N1—C1—C12—C11	175.21 (13)
C7—S1—C3—N2	−174.88 (14)	C12—C1—C2—N2	179.18 (12)
C7—S1—C3—C4	−0.26 (13)	N1—C1—C2—C9	−174.08 (13)
C5—N1—C1—C12	141.77 (14)	N1—C1—C2—N2	5.2 (2)
C1—N1—C5—N3	−171.03 (12)	C1—C2—C9—C10	0.1 (2)
C5—N1—C1—C2	−44.2 (2)	N2—C2—C9—C10	−179.24 (14)
C1—N1—C5—C4	4.2 (2)	N2—C3—C4—C5	−3.0 (2)
C3—N2—C2—C9	−121.43 (15)	S1—C3—C4—C6	0.02 (18)
C2—N2—C3—C4	−59.87 (19)	N2—C3—C4—C6	174.48 (15)
C2—N2—C3—S1	114.00 (14)	S1—C3—C4—C5	−177.47 (11)
C3—N2—C2—C1	59.26 (17)	C6—C4—C5—N1	−139.74 (16)
C13—N3—C16—C15	−56.26 (15)	C6—C4—C5—N3	35.6 (2)
C16—N3—C13—C14	56.41 (14)	C3—C4—C5—N3	−147.36 (14)
C13—N3—C5—N1	−142.72 (13)	C3—C4—C6—C7	0.3 (2)
C16—N3—C5—C4	−171.25 (12)	C5—C4—C6—C7	177.65 (15)
C5—N3—C16—C15	153.70 (13)	C3—C4—C5—N1	37.4 (2)
C5—N3—C13—C14	−154.18 (12)	C4—C6—C7—C8	−178.57 (18)
C16—N3—C5—N1	4.39 (18)	C4—C6—C7—S1	−0.51 (19)
C13—N3—C5—C4	41.64 (16)	C2—C9—C10—C11	−0.6 (2)
C15—N4—C14—C13	58.48 (15)	C9—C10—C11—C12	1.1 (2)
C14—N4—C15—C16	−59.03 (15)	C10—C11—C12—C1	−1.2 (2)
C17—N4—C15—C16	178.80 (14)	N3—C13—C14—N4	−57.44 (15)
C17—N4—C14—C13	−179.49 (15)	N4—C15—C16—N3	57.77 (16)
C2—C1—C12—C11	0.7 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···N1^i	0.82	2.36	3.162 (3)	165
O1W—H2AW···O1W^ii	0.82 (4)	2.13 (4)	2.923 (2)	162 (4)
O1W—H1W···N4^iii	0.91 (2)	1.91 (2)	2.8145 (16)	175 (2)
N2—H2···O1W	0.89 (2)	2.04 (2)	2.926 (2)	172.5 (15)
O1W—H2BW···O1	0.82 (5)	2.12 (5)	2.931 (3)	170 (6)

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

(III) 2-Methyl-4-(4-methylpiperazin-1-yl)-10H-thieno[2,3-b][1,5]benzodiazepine propan-2-one hemisolvate monohydrate

Crystal data

C17H20N4S·0.5C3H6O·H2O	F(000) = 1536
Mr = 359.50	Dx = 1.258 Mg m^−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2yc	Cell parameters from 928 reflections
a = 24.5759 (14) Å	θ = 3.4–22.0°
b = 12.5608 (5) Å	µ = 0.19 mm^−1
c = 15.1607 (9) Å	T = 296 K
β = 125.790 (9)°	Needle, yellow
V = 3796.3 (6) Å^3	0.50 × 0.35 × 0.25 mm
Z = 8

Data collection

Kuma KM-4 CCD area-detector diffractometer	3339 independent reflections
Graphite monochromator	1727 reflections with I > 2σ(I)
Detector resolution: 8.2356 pixels mm^-1	Rint = 0.045
ω scans	θmax = 25.0°, θmin = 1.9°
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)	h = −29→29
Tmin = 0.91, Tmax = 0.96	k = −14→14
21646 measured reflections	l = −18→16

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) = 0.090	w = 1/[σ^2(Fo^2) + (0.0497P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 0.82	(Δ/σ)max = 0.001
3339 reflections	Δρmax = 0.32 e Å^−3
261 parameters	Δρmin = −0.23 e Å^−3
27 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^* = kFc[1+0.001Fc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0008 (2)

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement on F² for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The observed criterion of F² > σ(F²) is used only for calculating -R-factor-obs etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
S1	0.79174 (3)	0.85138 (5)	0.74769 (5)	0.0564 (2)
N1	0.66840 (9)	0.62822 (12)	0.81453 (14)	0.0413 (6)
N2	0.68726 (9)	0.70939 (14)	0.65339 (16)	0.0466 (7)
N3	0.77255 (8)	0.58236 (12)	0.96401 (13)	0.0410 (6)
N4	0.85188 (9)	0.44914 (13)	1.14918 (13)	0.0485 (7)
C1	0.62214 (10)	0.69377 (15)	0.72647 (16)	0.0390 (8)
C2	0.62767 (11)	0.73030 (16)	0.64520 (17)	0.0415 (8)
C3	0.74471 (11)	0.74987 (15)	0.74837 (18)	0.0410 (8)
C4	0.76667 (10)	0.72348 (15)	0.85075 (17)	0.0372 (8)
C5	0.73247 (11)	0.64219 (15)	0.87141 (16)	0.0378 (8)
C6	0.82307 (11)	0.78578 (16)	0.92993 (18)	0.0458 (8)
C7	0.84275 (11)	0.85744 (17)	0.88792 (18)	0.0504 (8)
C8	0.89860 (12)	0.9369 (2)	0.9459 (2)	0.0800 (11)
C9	0.57518 (12)	0.78484 (18)	0.55675 (18)	0.0568 (9)
C10	0.51739 (12)	0.8058 (2)	0.5481 (2)	0.0647 (10)
C11	0.51131 (12)	0.77185 (18)	0.6273 (2)	0.0587 (9)
C12	0.56270 (11)	0.71583 (17)	0.71474 (18)	0.0476 (8)
C13	0.83733 (10)	0.54160 (16)	0.99533 (16)	0.0456 (8)
C14	0.88249 (11)	0.52317 (17)	1.11582 (17)	0.0521 (8)
C15	0.78783 (11)	0.49350 (17)	1.11809 (17)	0.0516 (9)
C16	0.74133 (10)	0.51111 (16)	0.99766 (16)	0.0453 (8)
C17	0.89617 (13)	0.4294 (2)	1.26682 (18)	0.0778 (11)
O1	0.5214 (7)	0.7243 (5)	0.2988 (9)	0.361 (10)	0.500
C18	0.5020 (5)	0.6374 (4)	0.2577 (8)	0.186 (5)	0.500
C19	0.5379 (5)	0.5721 (10)	0.2213 (11)	0.220 (9)	0.500
C20	0.4321 (4)	0.5962 (7)	0.2136 (9)	0.153 (6)	0.500
O1W	0.68035 (12)	0.75683 (15)	0.45941 (18)	0.0784 (9)
H2	0.6832 (10)	0.7259 (14)	0.5923 (17)	0.045 (7)*
H6	0.84450	0.77760	1.00430	0.0550*
H8A	0.91920	0.93330	1.02260	0.1200*	0.500
H8B	0.94010	0.90070	0.99670	0.1200*	0.500
H8C	0.93140	0.92120	0.93240	0.1200*	0.500
H8D	0.90180	0.97450	0.89400	0.1200*	0.500
H8E	0.88100	1.00720	0.91980	0.1200*	0.500
H8F	0.88970	0.98660	0.98420	0.1200*	0.500
H9	0.57900	0.80770	0.50230	0.0680*
H10	0.48250	0.84310	0.48850	0.0780*
H11	0.47250	0.78650	0.62230	0.0700*
H12	0.55760	0.69200	0.76760	0.0570*
H13A	0.85790	0.59240	0.97500	0.0550*
H13B	0.83080	0.47530	0.95740	0.0550*
H14A	0.92500	0.49450	1.13590	0.0620*
H14B	0.89130	0.59040	1.15340	0.0620*
H15A	0.79570	0.56060	1.15550	0.0620*
H15B	0.76710	0.44510	1.14020	0.0620*
H16A	0.73130	0.44360	0.96000	0.0540*
H16B	0.69960	0.54180	0.97890	0.0540*
H17A	0.90500	0.49540	1.30510	0.1160*
H17B	0.93760	0.39930	1.28580	0.1160*
H17C	0.87480	0.38080	1.28650	0.1160*
H19A	0.54250	0.61390	0.17300	0.3300*	0.500
H19B	0.51230	0.50930	0.18430	0.3300*	0.500
H19C	0.58150	0.55210	0.28370	0.3300*	0.500
H20A	0.42690	0.59270	0.27150	0.2290*	0.500
H20B	0.42630	0.52640	0.18340	0.2290*	0.500
H20C	0.39900	0.64350	0.15800	0.2290*	0.500
H2AW	0.7207 (8)	0.750 (6)	0.489 (6)	0.1180*	0.500
H1W	0.6670 (15)	0.8128 (13)	0.425 (2)	0.1180*
H2BW	0.656 (3)	0.713 (4)	0.412 (4)	0.1180*	0.500

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0530 (4)	0.0645 (4)	0.0565 (4)	−0.0010 (3)	0.0347 (4)	0.0150 (3)
N1	0.0347 (11)	0.0482 (10)	0.0370 (11)	0.0027 (9)	0.0187 (10)	0.0052 (9)
N2	0.0475 (13)	0.0618 (12)	0.0356 (13)	0.0015 (10)	0.0271 (12)	0.0013 (10)
N3	0.0354 (11)	0.0453 (10)	0.0430 (11)	0.0065 (9)	0.0233 (10)	0.0131 (9)
N4	0.0515 (12)	0.0427 (11)	0.0359 (12)	0.0013 (9)	0.0169 (10)	0.0078 (9)
C1	0.0354 (14)	0.0413 (12)	0.0352 (14)	−0.0033 (10)	0.0178 (12)	−0.0030 (10)
C2	0.0372 (14)	0.0474 (13)	0.0338 (13)	−0.0013 (11)	0.0174 (12)	−0.0015 (10)
C3	0.0404 (14)	0.0435 (12)	0.0440 (15)	0.0058 (10)	0.0275 (13)	0.0046 (11)
C4	0.0336 (13)	0.0377 (12)	0.0372 (14)	0.0050 (10)	0.0190 (12)	0.0075 (10)
C5	0.0408 (14)	0.0385 (12)	0.0358 (13)	0.0035 (11)	0.0234 (12)	0.0019 (11)
C6	0.0425 (14)	0.0466 (13)	0.0420 (14)	0.0069 (11)	0.0211 (13)	0.0099 (11)
C7	0.0420 (14)	0.0467 (13)	0.0541 (15)	0.0000 (12)	0.0234 (13)	0.0083 (12)
C8	0.0642 (19)	0.0691 (17)	0.085 (2)	−0.0201 (15)	0.0314 (17)	0.0073 (15)
C9	0.0518 (16)	0.0713 (16)	0.0390 (15)	−0.0027 (14)	0.0219 (14)	0.0068 (13)
C10	0.0397 (17)	0.0845 (18)	0.0464 (17)	0.0090 (13)	0.0119 (14)	0.0162 (14)
C11	0.0349 (14)	0.0756 (17)	0.0554 (17)	0.0051 (13)	0.0206 (14)	0.0028 (14)
C12	0.0375 (14)	0.0616 (15)	0.0410 (14)	−0.0006 (12)	0.0214 (13)	0.0019 (11)
C13	0.0408 (14)	0.0463 (13)	0.0464 (15)	0.0073 (11)	0.0236 (12)	0.0086 (10)
C14	0.0420 (14)	0.0479 (14)	0.0511 (16)	0.0015 (11)	0.0187 (13)	0.0035 (11)
C15	0.0635 (17)	0.0485 (13)	0.0464 (16)	−0.0032 (13)	0.0341 (14)	0.0031 (12)
C16	0.0472 (14)	0.0462 (13)	0.0466 (15)	0.0024 (11)	0.0297 (13)	0.0080 (11)
C17	0.080 (2)	0.0792 (18)	0.0415 (17)	−0.0038 (16)	0.0172 (15)	0.0128 (14)
O1	0.432 (19)	0.422 (13)	0.387 (19)	−0.290 (15)	0.328 (17)	−0.286 (12)
C18	0.204 (10)	0.266 (11)	0.115 (7)	−0.202 (10)	0.109 (7)	−0.106 (9)
C19	0.225 (15)	0.255 (14)	0.282 (17)	−0.047 (12)	0.206 (14)	−0.153 (12)
C20	0.162 (9)	0.151 (8)	0.211 (12)	0.089 (8)	0.146 (10)	0.103 (9)
O1W	0.1297 (19)	0.0563 (11)	0.0840 (18)	0.0036 (14)	0.0820 (18)	0.0046 (10)

Geometric parameters (Å, º)

S1—C3	1.725 (3)	C6—H6	0.9300
S1—C7	1.726 (2)	C8—H8E	0.9600
O1—C18	1.208 (10)	C8—H8C	0.9600
O1W—H2BW	0.82 (5)	C8—H8D	0.9600
O1W—H2AW	0.82 (6)	C8—H8B	0.9600
O1W—H1W	0.821 (19)	C8—H8F	0.9600
N1—C5	1.291 (4)	C8—H8A	0.9600
N1—C1	1.406 (3)	C9—H9	0.9300
N2—C2	1.420 (4)	C10—H10	0.9300
N2—C3	1.396 (3)	C11—H11	0.9300
N3—C13	1.462 (3)	C12—H12	0.9300
N3—C16	1.452 (3)	C13—H13B	0.9700
N3—C5	1.374 (3)	C13—H13A	0.9700
N4—C14	1.460 (3)	C14—H14A	0.9700
N4—C15	1.464 (4)	C14—H14B	0.9700
N4—C17	1.469 (3)	C15—H15A	0.9700
N2—H2	0.90 (2)	C15—H15B	0.9700
C1—C12	1.392 (4)	C16—H16B	0.9700
C1—C2	1.394 (3)	C16—H16A	0.9700
C2—C9	1.381 (3)	C17—H17B	0.9600
C3—C4	1.353 (3)	C17—H17A	0.9600
C4—C5	1.468 (4)	C17—H17C	0.9600
C4—C6	1.424 (3)	C18—C19	1.525 (19)
C6—C7	1.345 (4)	C18—C20	1.524 (18)
C7—C8	1.497 (4)	C19—H19C	0.9600
C9—C10	1.373 (5)	C19—H19A	0.9600
C10—C11	1.362 (4)	C19—H19B	0.9600
C11—C12	1.375 (3)	C20—H20A	0.9600
C13—C14	1.500 (3)	C20—H20B	0.9600
C15—C16	1.499 (3)	C20—H20C	0.9600
C3—S1—C7	91.82 (12)	H8C—C8—H8F	141.00
H2AW—O1W—H1W	110 (6)	H8D—C8—H8E	56.00
H2AW—O1W—H2BW	116 (7)	H8D—C8—H8F	109.00
H1W—O1W—H2BW	102 (4)	H8E—C8—H8F	56.00
C1—N1—C5	123.2 (2)	H8A—C8—H8C	110.00
C2—N2—C3	113.1 (2)	H8A—C8—H8D	141.00
C13—N3—C16	111.64 (16)	H8A—C8—H8E	109.00
C5—N3—C16	119.1 (2)	C2—C9—H9	120.00
C5—N3—C13	121.1 (2)	C10—C9—H9	119.00
C14—N4—C15	108.72 (17)	C9—C10—H10	120.00
C14—N4—C17	111.2 (2)	C11—C10—H10	120.00
C15—N4—C17	110.4 (2)	C12—C11—H11	120.00
C3—N2—H2	114.6 (16)	C10—C11—H11	120.00
C2—N2—H2	112.4 (17)	C11—C12—H12	119.00
N1—C1—C2	126.1 (3)	C1—C12—H12	119.00
C2—C1—C12	117.3 (2)	N3—C13—H13A	110.00
N1—C1—C12	116.3 (2)	N3—C13—H13B	110.00
N2—C2—C9	120.4 (2)	C14—C13—H13A	110.00
N2—C2—C1	119.4 (2)	C14—C13—H13B	110.00
C1—C2—C9	120.2 (3)	H13A—C13—H13B	108.00
N2—C3—C4	125.4 (2)	N4—C14—H14B	110.00
S1—C3—N2	122.70 (17)	H14A—C14—H14B	108.00
S1—C3—C4	111.64 (18)	C13—C14—H14A	109.00
C5—C4—C6	126.8 (2)	C13—C14—H14B	109.00
C3—C4—C6	111.8 (2)	N4—C14—H14A	109.00
C3—C4—C5	121.4 (2)	C16—C15—H15B	109.00
N3—C5—C4	116.1 (2)	H15A—C15—H15B	108.00
N1—C5—C4	125.38 (19)	C16—C15—H15A	109.00
N1—C5—N3	118.3 (2)	N4—C15—H15A	109.00
C4—C6—C7	114.3 (2)	N4—C15—H15B	109.00
C6—C7—C8	128.9 (2)	N3—C16—H16A	110.00
S1—C7—C6	110.51 (18)	N3—C16—H16B	110.00
S1—C7—C8	120.57 (19)	C15—C16—H16A	110.00
C2—C9—C10	121.0 (3)	C15—C16—H16B	110.00
C9—C10—C11	119.8 (2)	H16A—C16—H16B	108.00
C10—C11—C12	119.9 (3)	N4—C17—H17C	109.00
C1—C12—C11	121.9 (2)	H17A—C17—H17C	109.00
N3—C13—C14	109.8 (2)	H17B—C17—H17C	110.00
N4—C14—C13	110.9 (2)	H17A—C17—H17B	109.00
N4—C15—C16	111.0 (2)	N4—C17—H17A	109.00
N3—C16—C15	109.6 (2)	N4—C17—H17B	109.00
C4—C6—H6	123.00	C19—C18—C20	113.6 (8)
C7—C6—H6	123.00	O1—C18—C19	122.4 (14)
C7—C8—H8D	109.00	O1—C18—C20	122.5 (13)
C7—C8—H8E	109.00	C18—C19—H19B	109.00
C7—C8—H8F	109.00	H19A—C19—H19C	109.00
H8A—C8—H8B	56.00	C18—C19—H19C	109.00
C7—C8—H8A	109.00	H19A—C19—H19B	109.00
C7—C8—H8B	110.00	C18—C19—H19A	109.00
C7—C8—H8C	109.00	H19B—C19—H19C	109.00
H8A—C8—H8F	56.00	C18—C20—H20C	109.00
H8B—C8—H8C	56.00	H20A—C20—H20C	109.00
H8B—C8—H8D	109.00	H20B—C20—H20C	109.00
H8B—C8—H8E	141.00	H20A—C20—H20B	109.00
H8B—C8—H8F	109.00	C18—C20—H20A	109.00
H8C—C8—H8D	56.00	C18—C20—H20B	110.00
H8C—C8—H8E	109.00
C3—S1—C7—C6	−0.6 (2)	C12—C1—C2—C9	−0.8 (3)
C3—S1—C7—C8	−179.1 (2)	N1—C1—C12—C11	−174.8 (2)
C7—S1—C3—N2	174.7 (2)	C12—C1—C2—N2	−179.77 (18)
C7—S1—C3—C4	0.8 (2)	N1—C1—C2—C9	173.0 (2)
C5—N1—C1—C12	−142.4 (2)	N1—C1—C2—N2	−6.0 (3)
C1—N1—C5—N3	171.70 (19)	C1—C2—C9—C10	1.2 (3)
C5—N1—C1—C2	43.7 (3)	N2—C2—C9—C10	−179.8 (2)
C1—N1—C5—C4	−3.0 (4)	N2—C3—C4—C5	3.6 (4)
C3—N2—C2—C9	122.8 (2)	S1—C3—C4—C6	−0.7 (3)
C2—N2—C3—C4	59.4 (3)	N2—C3—C4—C6	−174.5 (2)
C2—N2—C3—S1	−113.7 (2)	S1—C3—C4—C5	177.29 (19)
C3—N2—C2—C1	−58.3 (3)	C6—C4—C5—N1	139.5 (3)
C13—N3—C16—C15	56.7 (2)	C6—C4—C5—N3	−35.3 (4)
C16—N3—C13—C14	−56.6 (2)	C3—C4—C5—N3	147.1 (2)
C13—N3—C5—N1	142.2 (2)	C3—C4—C6—C7	0.3 (3)
C16—N3—C5—C4	171.43 (19)	C5—C4—C6—C7	−177.6 (2)
C5—N3—C16—C15	−154.33 (19)	C3—C4—C5—N1	−38.1 (4)
C5—N3—C13—C14	155.17 (18)	C4—C6—C7—C8	178.7 (3)
C16—N3—C5—N1	−3.8 (3)	C4—C6—C7—S1	0.3 (3)
C13—N3—C5—C4	−42.6 (3)	C2—C9—C10—C11	−0.5 (4)
C15—N4—C14—C13	−59.0 (2)	C9—C10—C11—C12	−0.7 (4)
C14—N4—C15—C16	59.4 (2)	C10—C11—C12—C1	1.2 (3)
C17—N4—C15—C16	−178.35 (19)	N3—C13—C14—N4	57.8 (2)
C17—N4—C14—C13	179.2 (2)	N4—C15—C16—N3	−58.3 (2)
C2—C1—C12—C11	−0.4 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1W—H2AW···O1W^i	0.82 (6)	2.08 (6)	2.887 (5)	171 (6)
O1W—H1W···N4^ii	0.82 (2)	1.95 (2)	2.765 (3)	172 (4)
N2—H2···O1W	0.90 (2)	2.01 (2)	2.907 (3)	176 (2)
C20—H20C···O1W^iii	0.96	2.22	3.180 (11)	174

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