(5RS)-6H-Spiro­[pyrazolo­[1,5-c]quinazoline-5,4'-thio­chroman]: efficient synthesis under mild conditions, mol­ecular structure and supra­molecular assembly

Pyrazolo­[1,5-c]quinazolines are fused-quinazoline derivatives which have been reported as potential agents against neurological disorders. The normal synthesis routes to these compounds require harsh reaction conditions, long reaction times or multistep sequences. The title compound, C₁₈H₁₅N₃S, has been prepared under very mild conditions by condensation of thio­chroman-4-one with 5-(2-amino­phenyl)-1H-pyrazole, which had itself been prepared by the reaction of hydrazine hydrate with 4-hy­droxy­quinoline mediated by a brief period of microwave heating. Within the mol­ecule in the crystal structure, the reduced pyrimidine ring adopts an envelope conformation, whereas the thiane ring adopts a half-chair conformation. Mol­ecules are linked into sheets by a combination of one N-H...S hydrogen bond and two independent C-H...[pi](arene) hydrogen bonds, which utilize the same aryl ring as the acceptor, with one C-H bond donating to each face of the ring. Comparisons are made with some related compounds.

S1. Introduction

\ Pyrazolo­[1,5-c]quinazolines are fused-quinazoline derivatives which have been reported as potential agents against neurological disorders such as Alzheimer's, Parkinson's and Huntington's diseases (Varano et al., 2005; Asproni et al., 2011; Catarzi et al., 2013). The preparation of pyrazolo­[1,5-c]quinazoline derivatives has usually involved cyclo­condensation reactions between carbonyl compounds and 5-(2-amino­phenyl)-1H-pyrazoles. A number of different methods have been reported to build the amino­pyrazole from 4-hy­droxy­quinolines (Destevens & Blatter, 1962; Gerecke et al., 1994), o-nitro­chalcones (Colotta et al., 1996; Insuasty et al., 2003; Varano et al., 2005) or ethyl 4-(2-nitro­aryl)-2,4-dioxo­butano­ate (Varano et al., 2002, 2005), but all of these routes require harsh reaction conditions, long reaction times or multistep sequences. In the present work, we have developed an efficient two-step methodology using readily available starting materials which proceeds under mild conditions. In this procedure, 5-(2-amino­phenyl)-1H-pyrazole was obtained from the reaction between 4-hy­droxy­quinoline and hydrazine hydrate, mediated by a brief period of microwave irradiation. The desired spiro­pyrazolo­[1,5-c]quinazoline derivative was subsequently produced in almost qu­anti­tative yield at room temperature by reaction of the amino­pyrazole with thio­chroman-4-one to form the title compound, (5RS)-6H-spiro­[pyrazolo­[1,5-c]quinazoline-5,4'-\ thio­chroman, (I) (Fig. 1).

The conversion of 4-hy­droxy­quinoline to 5-(2-amino­phenyl)­pyrazole can most simply be envisaged as being initiated by a Michael-type addition of hydrazine to the 4-quinolone tautomer (A) (see Scheme 1) of 4-hy­droxy­quinoline to give the adduct (B), which undergoes ring-opening to form (C), from which the (amino­phenyl)­pyrazole (D) is formed by an intra­molecular dehydration reaction. Simple condensation at ambient temperature with thio­chroman-4-one (E) then produces the title compound, (I).

S2. Experimental

S2.1. Synthesis and crystallization

For the synthesis of the inter­mediate 5-(2-amino­phenyl)-1H-pyrazole, a mixture of 4-hy­droxy­quinoline (1 mmol) and an excess of hydrazine hydrate (7 mmol) was subjected to microwave irradiation at 450 K over a period of 20 min and a maximum power of 300 W. The mixture was then poured into cold water, and the resulting yellow solid product was collected by filtration, washed with water and used without further purification (yield 74%, m.p. 393–394 K). MS (EI, 70 eV) m/z (%) 159 (M⁺, 100), 130.

For the synthesis of the title compound, a mixture of 5-(2-amino­phenyl)-1H-pyrazole (0.25 mmol) and thio­chroman-4-one (0.25 mmol) in glacial acetic acid (1 ml) was stirred overnight at room temperature. After completion of the reaction, water (1 ml) was added to the reaction mixture and the product was extracted exhaustively with ethyl acetate. The combined organic fractions were dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to obtain the title compound, (I) (yield 98%, m.p. 467–469 K). MS (EI, 70 eV) m/z (%) 305 (M⁺, 46), 276 (100), 244 (38). Yellow crystals of (I) suitable for single-crystal X-ray diffraction were grown by slow evaporation, at ambient temperature and in the presence of air, of a solution in di­methyl sulfoxide.

S2.2. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1. All H atoms were located in difference maps. H atoms bonded to C atoms were then treated as riding in geometrically idealized positions, with C—H = 0.95 (aromatic and heteroaromatic) or 0.99 Å (CH₂) and with U_iso(H) = 1.2U_eq(C). For the H atom bonded to atom N6, the atomic coordinates were refined with U_iso(H) = 1.2U_eq(N), giving an N—H distance of 0.85 (2) Å. Four weak but badly outlying reflections (-12,6,9, -12,6,10, -13,5,10 and -13,5,12) were omitted from the final refinements.

S3. Comment

The molecule of (I) contains a stereogenic centre at atom C5 (Fig. 1) and the reference molecule was selected to be one having the R configuration at C5. However, the centrosymmetric space group confirms that (I) has crystallized as a racemic mixture.

For the ring containing atoms N4 and N6, the ring-puckering parameters (Cremer & Pople, 1975) indicate a ring conformation close to the envelope form (Table 2), while those for the ring containing atom S13 indicate a conformation close to the half-chair form. For the first of these rings, the five ring atoms other than C5 have a maximum deviation from their mean plane of only 0.0683 (10) Å for atom C10b, with an r.m.s. deviation of 0.052 Å, but atom C5 is displaced from this plane by 0.535 (2) Å. Thus, this ring is folded across the N4···N6 line into an envelope conformation. For the second ring, atoms C5, C19, C14 and S13 have a maximum deviation from their mean plane of only 0.0066 (10) Å for atom C19, but atoms C11 and C12 are displaced from this plane, one to either side of it, by 0.364 (3) and 0.460 (2) Å, respectively, confirming the presence of an almost ideal half-chair conformation.

The inter-atomic distances and inter-bond angles in (I) (Table 3) present a number of inter­esting features. Within the pyrazole ring, the C1—C2 and C1—C10b bond lengths differ by less than 0.02 Å, even though these bonds are formally single and double bonds, respectively. Similarly, the N4—C10b and C2—N3 bond lengths differ by only a little over 0.02 Å, even though, again, these are formally single and double bonds, respectively. These observations thus point to a significant degree of aromatic-type electron delocalization within this ring. A noteworthy feature of the C14–C19 ring is the wide difference between the pair of exocyclic S—C—C angles at atom C14, which differ by ca 10°. This behaviour is comparable with that observed in meth­oxy­arenes, in which the methyl C atom is effectively coplanar with the arene ring (Seip et al., 1973; Ferguson et al., 1996).

The geometry at amidic atom N6 is markedly pyramidal, with the sum of the inter-bond angles at N6 being ca 348° (Table 3), associated with a displacement of atom N6 from the C5/N6/C6a plane of 0.49 (2) Å. However, the degree of pyramidalization here is much less than that in simple acyclic amines, where the sum of the inter­bond angles is typically in the range 320–325°. Consistent with this, the N6—C6a bond length (Table 3) lies mid-way between the typical values for such bonds in those acyclic compounds of type ArNHR containing planar N atoms [mean value (Allen et al., 1987) 1.353 Å, upper quartile value 1.359 Å] and those containing pyramidal N atoms (mean value 1.419 Å, lower-quartile value 1.412 Å). The two C—S distances show the expected difference (Allen et al., 1987).

The molecules of (I) are linked into complex sheets by a combination of one N—H···S hydrogen bond and two independent but co-operative C—H···π(arene) hydrogen bonds (Table 4). The formation of the sheets is readily analysed in terms of two simple substructures (Ferguson et al., 1998a,b; Gregson et al., 2000). In the simpler of the two substructures, inversion-related pairs of molecules are linked by inversion-related N—H···S hydrogen bonds to form cyclic dimers characterized by an R₂²(12) (Bernstein et al., 1995) motif (Fig. 2), with the reference dimer centred across (0, 1/2, 1/2).

While two-coordinate S atoms of the type present in (I) have generally been regarded as rather weak acceptors of hydrogen bonds (Allen et al., 1997; Desiraju & Steiner, 1999), the N—H···S hydrogen bond observed in (I) is nearly linear, with an N···S distances somewhat less than the mean value for such contacts. It is also noteworthy that the N—H bond engages with the S atom, rather than with one of the pyrazole N atoms, as found in compounds (II)–(IV) (see Scheme 2) discussed below, or with one of the aryl rings as found in compound (V), also discussed below.

The more complex of the two substructures depends upon the co-operative actions of two independent C—H···π(arene) hydrogen bonds, both involving the same C6a/C7–C10/C10a aryl ring; one of these inter­actions has a rather short H···Cg distance associated with a nearly linear C—H···Cg arrangement, while the other is evidently somewhat weaker (Table 4). The combined action of these two hydrogen bonds generates a ribbon of edge-fused rings running parallel to the [010] direction (Fig. 3). The two C—H bonds acting as the hydrogen-bond donors approach the aryl ring on opposite faces, with the angle H12A···Cg1ⁱ···H9ⁱⁱ = 169.6° [symmetry codes: (i) x, y + 1, z; ii) -x + 1/2, y + 3/2, -z + 1/2]. This chain motif leads to the direct linkage of the R₂²(12) dimer (Fig. 2) centred at (0, 1/2, 1/2) to the four symmetry-related dimers centred at (1/2, 0, 0), (1/2, 1, 0), (-1/2, 0, 1) and (-1/2, 1, 1), so forming a complex sheet lying parallel to (101) (Fig. 4).

The structures of the reduced analogues, compounds (II)–(V) (see Scheme 2), whose structures were reported a few years ago (Low et al., 2002), provide some inter­esting contrasts with the structure of (I) reported here. Firstly, each of (II)–(V), where (II) and (III) are isostructural, contains two stereogenic centres at atoms C5 and C10b, and although it was not specifically noted in the original report, each compound crystallizes as a racemic mixture with the (5RS,10bRS) configuration. Secondly, the reduced pyrimidine ring in each of (II)–(V) adopts a half-chair conformation in which atoms N4, C10b, C10a and C6a are approximately coplanar, while atoms C5 and N6 are markedly displaced from this plane, one to either side of it; this is in contrast with the envelope conformation found for this ring in (I). In addition, in each of (II)–(V), the reduced pyrazole ring is folded across the C1···N4 line into an envelope conformation, as opposed to the planar pyrazole ring in (I). Thirdly, in each of (II)–(IV), but not (V), the primary motif in the supra­molecular assembly is a centrosymmetric R₂²(10) motif built from inversion-related N—H···N hydrogen bonds having atom N3 as the acceptor, while in (V), the molecules are linked into chains by an N—H···π(arene) hydrogen bond in which the acceptor is the brominated aryl ring.

Computing details

Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015), PLATON (Spek, 2009) and publCIF (Westrip, 2010).

Figures

	Fig. 1. The molecular structure of the R enantiomer of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. Part of the crystal structure of (I), showing the formation of a cyclic centrosymmetric R2^2(12) dimer built from N—H···S hydrogen bonds (dashed lines). For the sake of clarity, the unit-cell outline and H atoms bonded to C atoms have all been omitted. Atoms marked with an asterisk (*) are at the symmetry position (-x, -y + 1, -z + 1).
	Fig. 3. Part of the crystal structure of (I), showing the formation of a ribbon of edge-fused rings built from two independent C—H···π(arene) hydrogen bonds (dashed lines). For the sake of clarity, H atoms not involved in the motifs shown have been omitted. The S atoms marked with an asterisk (*), a hash (#) or a dollar sign ($) are at the symmetry positions (x, y + 1, z), (x, y - 1, z) and (-x + 1/2, y + 1/2, -z + 1/2), respectively.
	Fig. 4. A stereoview of part of the crystal structure of (I), showing the formation of a hydrogen-bonded sheet lying parallel to (101). Hydrogen bonds are shown as dashed lines. For the sake of clarity, H atoms not involved in the motifs shown have been omitted.

6H-Spiro[pyrazolo[1,5-c]quinazoline-5,4'-thiochroman]

Crystal data

C18H15N3S	F(000) = 640
Mr = 305.39	Dx = 1.419 Mg m^−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
a = 12.5223 (8) Å	Cell parameters from 4324 reflections
b = 7.6646 (4) Å	θ = 2.3–30.5°
c = 15.1729 (13) Å	µ = 0.23 mm^−1
β = 101.044 (4)°	T = 100 K
V = 1429.30 (17) Å^3	Block, yellow
Z = 4	0.14 × 0.12 × 0.12 mm

Data collection

Bruker D8 Venture diffractometer	3983 independent reflections
Radiation source: high brilliance microfocus sealed tube	3203 reflections with I > 2σ(I)
Multilayer monochromator	Rint = 0.042
φ and ω scans	θmax = 29.5°, θmin = 2.3°
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)	h = −17→15
Tmin = 0.904, Tmax = 0.973	k = −9→10
7190 measured reflections	l = −20→21

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)] = 0.045	Hydrogen site location: mixed
wR(F^2) = 0.121	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	w = 1/[σ^2(Fo^2) + (0.0358P)^2 + 0.850P] where P = (Fo^2 + 2Fc^2)/3
3983 reflections	(Δ/σ)max < 0.001
202 parameters	Δρmax = 0.61 e Å^−3
0 restraints	Δρmin = −0.41 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.

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

	x	y	z	Uiso*/Ueq
C1	0.46715 (13)	0.2261 (2)	0.51170 (11)	0.0128 (3)
H1	0.5226	0.1682	0.4880	0.015*
C2	0.48019 (13)	0.3409 (2)	0.58512 (11)	0.0144 (3)
H2	0.5489	0.3730	0.6197	0.017*
N3	0.38490 (11)	0.40023 (18)	0.60093 (9)	0.0120 (3)
N4	0.30980 (10)	0.31942 (17)	0.53709 (9)	0.0101 (3)
C5	0.19281 (12)	0.3672 (2)	0.51979 (11)	0.0102 (3)
N6	0.13605 (11)	0.20981 (18)	0.48111 (10)	0.0120 (3)
H6	0.0674 (18)	0.220 (3)	0.4775 (14)	0.014*
C6a	0.17187 (12)	0.1227 (2)	0.41148 (11)	0.0108 (3)
C7	0.10099 (13)	0.0252 (2)	0.34716 (11)	0.0139 (3)
H7	0.0250	0.0273	0.3465	0.017*
C8	0.14136 (14)	−0.0742 (2)	0.28445 (11)	0.0160 (3)
H8	0.0927	−0.1408	0.2416	0.019*
C9	0.25285 (14)	−0.0777 (2)	0.28345 (11)	0.0140 (3)
H9	0.2800	−0.1466	0.2406	0.017*
C10	0.32345 (13)	0.0212 (2)	0.34616 (11)	0.0127 (3)
H10	0.3991	0.0212	0.3452	0.015*
C10a	0.28460 (12)	0.1204 (2)	0.41048 (10)	0.0103 (3)
C10b	0.35548 (12)	0.2156 (2)	0.48139 (11)	0.0100 (3)
C11	0.17443 (13)	0.5187 (2)	0.45225 (11)	0.0137 (3)
H11A	0.2068	0.4882	0.3997	0.016*
H11B	0.0953	0.5352	0.4310	0.016*
C12	0.22383 (14)	0.6881 (2)	0.49234 (12)	0.0150 (3)
H12A	0.2221	0.7757	0.4441	0.018*
H12B	0.3007	0.6686	0.5212	0.018*
S13	0.14908 (3)	0.76938 (5)	0.57466 (3)	0.01409 (12)
C14	0.13964 (12)	0.5772 (2)	0.63733 (11)	0.0124 (3)
C15	0.11157 (13)	0.6033 (2)	0.72171 (12)	0.0162 (3)
H15	0.0982	0.7181	0.7407	0.019*
C16	0.10324 (14)	0.4629 (3)	0.77739 (12)	0.0181 (4)
H16	0.0847	0.4820	0.8345	0.022*
C17	0.12188 (13)	0.2932 (2)	0.75024 (12)	0.0166 (3)
H17	0.1160	0.1968	0.7883	0.020*
C18	0.14920 (13)	0.2678 (2)	0.66657 (11)	0.0139 (3)
H18	0.1619	0.1526	0.6480	0.017*
C19	0.15854 (12)	0.4072 (2)	0.60902 (11)	0.0114 (3)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0088 (7)	0.0124 (7)	0.0174 (8)	−0.0002 (6)	0.0032 (6)	−0.0013 (6)
C2	0.0100 (7)	0.0142 (7)	0.0183 (8)	−0.0019 (6)	0.0009 (6)	−0.0014 (6)
N3	0.0100 (6)	0.0112 (6)	0.0139 (6)	−0.0014 (5)	0.0001 (5)	−0.0007 (5)
N4	0.0077 (6)	0.0092 (6)	0.0132 (6)	−0.0006 (5)	0.0016 (5)	−0.0016 (5)
C5	0.0084 (6)	0.0091 (7)	0.0129 (7)	0.0013 (5)	0.0014 (5)	−0.0013 (6)
N6	0.0060 (6)	0.0117 (6)	0.0181 (7)	−0.0005 (5)	0.0022 (5)	−0.0048 (5)
C6a	0.0114 (7)	0.0069 (6)	0.0131 (7)	0.0007 (5)	0.0002 (5)	−0.0002 (6)
C7	0.0111 (7)	0.0120 (7)	0.0171 (8)	0.0005 (6)	−0.0006 (6)	−0.0013 (6)
C8	0.0186 (8)	0.0135 (7)	0.0139 (8)	−0.0005 (6)	−0.0020 (6)	−0.0012 (6)
C9	0.0179 (8)	0.0123 (7)	0.0121 (7)	0.0014 (6)	0.0037 (6)	−0.0023 (6)
C10	0.0139 (7)	0.0112 (7)	0.0136 (7)	0.0011 (6)	0.0041 (6)	0.0006 (6)
C10a	0.0101 (7)	0.0079 (6)	0.0128 (7)	0.0000 (5)	0.0019 (5)	0.0015 (6)
C10b	0.0098 (7)	0.0076 (6)	0.0133 (7)	0.0003 (5)	0.0040 (5)	−0.0008 (6)
C11	0.0151 (7)	0.0115 (7)	0.0141 (7)	0.0031 (6)	0.0021 (6)	0.0015 (6)
C12	0.0163 (8)	0.0105 (7)	0.0186 (8)	0.0004 (6)	0.0045 (6)	0.0029 (6)
S13	0.01358 (19)	0.00879 (18)	0.0192 (2)	0.00161 (14)	0.00152 (14)	−0.00145 (15)
C14	0.0082 (7)	0.0119 (7)	0.0163 (8)	−0.0001 (6)	0.0003 (6)	−0.0011 (6)
C15	0.0118 (7)	0.0180 (8)	0.0186 (8)	0.0025 (6)	0.0025 (6)	−0.0047 (7)
C16	0.0122 (7)	0.0287 (9)	0.0139 (8)	0.0002 (7)	0.0040 (6)	−0.0021 (7)
C17	0.0109 (7)	0.0216 (8)	0.0171 (8)	−0.0029 (6)	0.0024 (6)	0.0034 (7)
C18	0.0118 (7)	0.0130 (7)	0.0167 (8)	−0.0020 (6)	0.0021 (6)	0.0018 (6)
C19	0.0087 (7)	0.0123 (7)	0.0130 (7)	0.0013 (5)	0.0014 (5)	−0.0015 (6)

Geometric parameters (Å, º)

C1—C2	1.405 (2)	C10a—C6a	1.415 (2)
C1—H1	0.9500	C10—H10	0.9500
C2—N3	1.341 (2)	C10a—C10b	1.453 (2)
C2—H2	0.9500	C11—C12	1.515 (2)
N3—N4	1.3628 (18)	C11—H11A	0.9900
N4—C10b	1.3637 (19)	C11—H11B	0.9900
C10b—C1	1.388 (2)	C12—S13	1.8088 (17)
N4—C5	1.4840 (19)	C12—H12A	0.9900
C5—N6	1.465 (2)	C12—H12B	0.9900
C5—C19	1.528 (2)	S13—C14	1.7694 (17)
C5—C11	1.536 (2)	C14—C15	1.406 (2)
N6—C6a	1.395 (2)	C14—C19	1.406 (2)
N6—H6	0.85 (2)	C15—C16	1.385 (3)
C6a—C7	1.402 (2)	C15—H15	0.9500
C7—C8	1.388 (2)	C16—C17	1.397 (3)
C7—H7	0.9500	C16—H16	0.9500
C8—C9	1.399 (2)	C17—C18	1.390 (2)
C8—H8	0.9500	C17—H17	0.9500
C9—C10	1.393 (2)	C18—C19	1.399 (2)
C9—H9	0.9500	C18—H18	0.9500
C10—C10a	1.396 (2)
C10b—C1—C2	104.81 (14)	C6a—C10a—C10b	117.07 (14)
C10b—C1—H1	127.6	N4—C10b—C1	106.06 (14)
C2—C1—H1	127.6	N4—C10b—C10a	118.85 (13)
N3—C2—C1	112.47 (14)	C1—C10b—C10a	135.06 (14)
N3—C2—H2	123.8	C12—C11—C5	112.49 (14)
C1—C2—H2	123.8	C12—C11—H11A	109.1
C2—N3—N4	103.61 (13)	C5—C11—H11A	109.1
N3—N4—C10b	113.04 (13)	C12—C11—H11B	109.1
N3—N4—C5	122.47 (12)	C5—C11—H11B	109.1
C10b—N4—C5	123.47 (13)	H11A—C11—H11B	107.8
N6—C5—N4	104.73 (12)	C11—C12—S13	110.30 (11)
N6—C5—C19	108.86 (13)	C11—C12—H12A	109.6
N4—C5—C19	109.16 (12)	S13—C12—H12A	109.6
N6—C5—C11	110.85 (13)	C11—C12—H12B	109.6
N4—C5—C11	108.74 (12)	S13—C12—H12B	109.6
C19—C5—C11	114.08 (13)	H12A—C12—H12B	108.1
C6a—N6—C5	119.75 (13)	C12—S13—C14	100.44 (8)
C6a—N6—H6	117.3 (14)	C15—C14—C19	119.77 (16)
C5—N6—H6	111.0 (14)	S13—C14—C15	115.15 (13)
N6—C6a—C7	121.99 (14)	S13—C14—C19	125.08 (13)
N6—C6a—C10a	118.70 (14)	C16—C15—C14	120.40 (16)
C7—C6a—C10a	119.08 (14)	C16—C15—H15	119.8
C8—C7—C6a	120.30 (15)	C14—C15—H15	119.8
C8—C7—H7	119.8	C15—C16—C17	120.49 (16)
C6a—C7—H7	119.8	C15—C16—H16	119.8
C7—C8—C9	120.87 (15)	C17—C16—H16	119.8
C7—C8—H8	119.6	C18—C17—C16	118.93 (16)
C9—C8—H8	119.6	C18—C17—H17	120.5
C10—C9—C8	119.10 (15)	C16—C17—H17	120.5
C10—C9—H9	120.5	C17—C18—C19	121.85 (16)
C8—C9—H9	120.5	C17—C18—H18	119.1
C9—C10—C10a	120.90 (15)	C19—C18—H18	119.1
C9—C10—H10	119.6	C18—C19—C14	118.55 (15)
C10a—C10—H10	119.6	C18—C19—C5	118.11 (14)
C10—C10a—C6a	119.74 (14)	C14—C19—C5	123.30 (14)
C10—C10a—C10b	123.08 (14)
C10b—C1—C2—N3	−0.11 (19)	C2—C1—C10b—N4	−0.70 (17)
C1—C2—N3—N4	0.87 (18)	C2—C1—C10b—C10a	−178.50 (17)
C2—N3—N4—C10b	−1.35 (17)	C10—C10a—C10b—N4	175.16 (14)
C2—N3—N4—C5	−170.21 (14)	C6a—C10a—C10b—N4	−8.6 (2)
N3—N4—C5—N6	−154.82 (13)	C10—C10a—C10b—C1	−7.3 (3)
C10b—N4—C5—N6	37.49 (19)	C6a—C10a—C10b—C1	169.03 (18)
N3—N4—C5—C19	−38.39 (19)	N6—C5—C11—C12	175.12 (13)
C10b—N4—C5—C19	153.92 (14)	N4—C5—C11—C12	−70.26 (16)
N3—N4—C5—C11	86.64 (17)	C19—C5—C11—C12	51.82 (18)
C10b—N4—C5—C11	−81.05 (17)	C5—C11—C12—S13	−69.61 (15)
N4—C5—N6—C6a	−48.14 (18)	C11—C12—S13—C14	47.35 (13)
C19—C5—N6—C6a	−164.78 (13)	C12—S13—C14—C15	163.58 (13)
C11—C5—N6—C6a	68.96 (18)	C12—S13—C14—C19	−15.97 (16)
C5—N6—C6a—C7	−151.73 (15)	C19—C14—C15—C16	0.5 (2)
C5—N6—C6a—C10a	33.8 (2)	S13—C14—C15—C16	−179.08 (13)
N6—C6a—C7—C8	−173.34 (15)	C14—C15—C16—C17	−0.4 (3)
C10a—C6a—C7—C8	1.1 (2)	C15—C16—C17—C18	0.2 (3)
C6a—C7—C8—C9	−0.7 (3)	C16—C17—C18—C19	0.0 (2)
C7—C8—C9—C10	−0.4 (3)	C17—C18—C19—C14	0.0 (2)
C8—C9—C10—C10a	1.2 (2)	C17—C18—C19—C5	177.90 (14)
C9—C10—C10a—C6a	−0.8 (2)	C15—C14—C19—C18	−0.3 (2)
C9—C10—C10a—C10b	175.36 (15)	S13—C14—C19—C18	179.24 (12)
N6—C6a—C10a—C10	174.30 (14)	C15—C14—C19—C5	−178.04 (14)
C7—C6a—C10a—C10	−0.3 (2)	S13—C14—C19—C5	1.5 (2)
N6—C6a—C10a—C10b	−2.1 (2)	N6—C5—C19—C18	41.66 (18)
C7—C6a—C10a—C10b	−176.72 (14)	N4—C5—C19—C18	−72.12 (17)
N3—N4—C10b—C1	1.32 (18)	C11—C5—C19—C18	166.03 (14)
C5—N4—C10b—C1	170.05 (14)	N6—C5—C19—C14	−140.59 (15)
N3—N4—C10b—C10a	179.55 (13)	N4—C5—C19—C14	105.64 (17)
C5—N4—C10b—C10a	−11.7 (2)	C11—C5—C19—C14	−16.2 (2)

Hydrogen-bond geometry (Å, º)

Cg1 represents the centroid of the ring C6a/C7–C10/C10a.

D—H···A	D—H	H···A	D···A	D—H···A
N6—H6···S13^i	0.85 (2)	2.68 (2)	3.5117 (15)	166.3 (19)
C9—H9···Cg1^ii	0.95	2.87	3.7171 (17)	149
C12—H12A···Cg1^iii	0.99	2.39	3.3670 (18)	170

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