Lurasidone hydro­chloride

Zhang, H.; Wang, H.; Zhu, X.; Yuan, Z.; Jiang, H.

doi:10.1107/S1600536812012883

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 68| Part 5| May 2012| Page o1357

doi:10.1107/S1600536812012883

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access

Lurasidone hydrochloride

Hua Zhang,^a Hubo Wang,^a Xueyan Zhu,^a Zhedong Yuan ^a ^* and Huijuan Jiang ^a

^aShanghai Institute of Pharmaceutical Industry, No. 1111, North ZhongShan No.1 Road, HongKou District, Shanghai 200437, People's Republic of China
^*Correspondence e-mail: gongyierzu@126.com

(Received 29 February 2012; accepted 24 March 2012; online 13 April 2012)

In the crystal structure of the title compound, C₂₈H₃₇N₄O₂S⁺·Cl⁻ [systematic name: 4-(1,2-benzothiazol-3-yl)-1-({2-[(3,5-dioxo-4-azatricyclo[5.2.1.0^2,6]decan-4-yl)methyl]cyclohexyl}methyl)piperazin-1-ium chloride], the anions and cations are linked by N—H⋯Cl hydrogen bonds. The crystal structure is further stabilized by C—H⋯π and C—H⋯O interactions.

Related literature

For the background to the biological activity of the title compound, an antipsychotic drug, see: Ishibashi et al. (2002 ); Ishiyama et al. (2003 ); Ohno et al. (1997 ).

Experimental

Crystal data

C₂₈H₃₇N₄O₂S⁺·Cl⁻
M_r = 529.13
Orthorhombic, P 2₁ 2₁ 2₁
a = 11.2039 (10) Å
b = 12.2665 (11) Å
c = 19.9774 (18) Å
V = 2745.5 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.25 mm⁻¹
T = 293 K
0.22 × 0.12 × 0.10 mm

Data collection

Bruker SMART CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2000 ) T_min = 0.452, T_max = 1.000
15020 measured reflections
5384 independent reflections
4649 reflections with I > 2σ(I)
R_int = 0.028

Refinement

R[F² > 2σ(F²)] = 0.047
wR(F²) = 0.108
S = 1.10
5384 reflections
329 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.14 e Å⁻³
Absolute structure: Flack (1983 ), 2338 Friedel pairs
Flack parameter: 0.03 (6)

Table 1
Hydrogen-bond geometry (Å, °)

Cg is the centroid of the S1/ N4/C22/C23/C28 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2A⋯Cl1	0.80 (2)	2.15 (2)	2.9426 (19)	168 (2)
C21—H21A⋯O1ⁱ	0.97	2.38	3.289 (3)	156
C5—H5A⋯Cgⁱⁱ	0.97	2.89	3.802 (4)	157
Symmetry codes: (i) $[x+{\script{1\over 2}}, -y+{\script{3\over 2}}, -z+1]$ ; (ii) $[-x+{\script{1\over 2}}, -y+1, z-{\script{1\over 2}}]$ .

Data collection: SMART (Bruker, 2000); cell refinement: SAINT (Bruker, 2000); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536812012883/bt5835sup1.cif

Supporting information file. DOI: 10.1107/S1600536812012883/bt5835Isup2.cml

Structure factors: contains datablock I. DOI: 10.1107/S1600536812012883/bt5835Isup3.hkl

checkCIF report

Comment top

Lurasidone hydrochloride is a benzisothiazole derivative and an atypical antipsychotic drug. This drug has high affinities for dopamine D₂ (K_i =1.68nM), serotonin 5-HT_{2 A} (K_i =2.03nM), 5-HT_{1 A} (K_i =6.75nM), 5-HT₇ receptors (K_i =0.495nM), and α_2c adrenoceptor (K_i =10.8nM), but only weak or negligible interactions with serotonin 5-HT_2c, histamine H₁, acetylcholine M₁ receptors, and α ₁ adrenoceptor (Ishibashi et al., 2002; Ishiyama et al., 2003). Interestingly, despite its potent D₂-blocking actions in vivo, Lurasidone has little propensity to induce extrapyramidal symptoms (Ohno et al., 1997).

The United States Food and Drug Administration (US FDA) approved Lurasidone hydrochloride (brand name: Latuda) in 2010 as an immediate release oral tablet for the treatment of schizophrenia. Lurasidone hydrochloride was developed by Dainippon Sumitomo Pharma in collaboration with Merck Research Laboratories during the initial IND stages. No data about crystal structure of Lurasidone hydrochloride has been reported yet.

Lurasidone hydrochloride consists of six chiral centres, e. g. C1, C2, C11, C12, C15 and C16. Currently, the clinically used form is a single isomer. The crystal structure of the title compound is built up of discrete lurasidium anions and chloride cations (Fig. 1).

There are two systems of hydrogen-bond interactions, viz. N2—H2A···Cl1 and C21—H21A···O1Aⁱ [symmetry code: (i) x + 1/2, -y + 3/2, -z + 1] (Table 1 and Fig. 2).

The crystal structure is further stabilized by weak C—H···π interactions [symmetry code: 1/2 - x, 1 - y, -1/2 + z] between the cyclohexyl (C5—H5A) and the isothiazole ring.

Related literature top

For the background to the biological activity of the title compound, an antipsychotic drug, see: Ishibashi et al. (2002); Ishiyama et al. (2003); Ohno et al. (1997).

Experimental top

Lurasidone hydrochloride (10 g, 18.9 mmole) was dissolved in a hot solution in a 3:1 mixture of acetone and water. After cooling to ambient temperature, the solvent was allowed to evaporate slowly. Colourless crystals of (1) appeared after 5 days.

Computing details top

Data collection: SMART (Bruker, 2000); cell refinement: SAINT (Bruker, 2000); data reduction: SAINT (Bruker, 2000); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top

	Fig. 1. The molecular structure of lurasidone hydrochloride, showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 2. Part of the crystal packing of the title compound, showing the N—H···Cl and C—H···O hydrogen bonds. Hydrogen bonds are shown as dashed lines and H atoms not involved in hydrogen bonding have been omitted for clarity. Only atoms involved in hydrogen bonding have been labelled.

4-(1,2-benzothiazol-3-yl)-1-({2-[(3,5-dioxo-4-azatricyclo[5.2.1.0^2,6]decan- 4-yl)methyl]cyclohexyl}methyl)piperazin-1-ium chloride top

Crystal data top

C₂₈H₃₇N₄O₂S⁺·Cl⁻	F(000) = 1128
M_r = 529.13	D_x = 1.280 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 3969 reflections
a = 11.2039 (10) Å	θ = 4.9–45.2°
b = 12.2665 (11) Å	µ = 0.25 mm⁻¹
c = 19.9774 (18) Å	T = 293 K
V = 2745.5 (4) Å³	Prismatic, colourless
Z = 4	0.22 × 0.12 × 0.10 mm

Data collection top

Bruker SMART CCD area-detector diffractometer	5384 independent reflections
Radiation source: fine-focus sealed tube	4649 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.028
phi and ω scans	θ_max = 26.0°, θ_min = 2.0°
Absorption correction: multi-scan (SADABS; Bruker, 2000)	h = −13→13
T_min = 0.452, T_max = 1.000	k = −15→15
15020 measured reflections	l = −24→13

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.047	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.108	w = 1/[σ²(F_o²) + (0.0569P)² + 0.004P] where P = (F_o² + 2F_c²)/3
S = 1.10	(Δ/σ)_max = 0.001
5384 reflections	Δρ_max = 0.24 e Å⁻³
329 parameters	Δρ_min = −0.14 e Å⁻³
1 restraint	Absolute structure: Flack (1983), 2338 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.03 (6)

Crystal data top

C₂₈H₃₇N₄O₂S⁺·Cl⁻	V = 2745.5 (4) Å³
M_r = 529.13	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 11.2039 (10) Å	µ = 0.25 mm⁻¹
b = 12.2665 (11) Å	T = 293 K
c = 19.9774 (18) Å	0.22 × 0.12 × 0.10 mm

Data collection top

Bruker SMART CCD area-detector diffractometer	5384 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2000)	4649 reflections with I > 2σ(I)
T_min = 0.452, T_max = 1.000	R_int = 0.028
15020 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.047	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.108	Δρ_max = 0.24 e Å⁻³
S = 1.10	Δρ_min = −0.14 e Å⁻³
5384 reflections	Absolute structure: Flack (1983), 2338 Friedel pairs
329 parameters	Absolute structure parameter: 0.03 (6)
1 restraint

Special details top

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 (Å²) top

	x	y	z	U_iso*/U_eq
S1	0.68064 (7)	0.23143 (5)	0.79887 (4)	0.0593 (2)
Cl1	0.24826 (6)	0.28761 (6)	0.52740 (4)	0.0704 (2)
N1	0.43096 (19)	0.85877 (16)	0.44646 (11)	0.0484 (5)
N2	0.44531 (15)	0.44620 (14)	0.52716 (10)	0.0353 (4)
N3	0.54606 (16)	0.38440 (15)	0.65254 (10)	0.0406 (5)
N4	0.60954 (19)	0.24766 (16)	0.72566 (11)	0.0499 (5)
O1	0.25234 (18)	0.94287 (16)	0.46631 (10)	0.0662 (5)
O2	0.62622 (17)	0.81973 (17)	0.42244 (12)	0.0748 (6)
C1	0.3506 (2)	0.67528 (19)	0.41447 (13)	0.0455 (6)
H1	0.4094	0.6737	0.3782	0.055*
C2	0.3346 (2)	0.55930 (19)	0.44089 (12)	0.0438 (6)
H2	0.2824	0.5628	0.4802	0.053*
C3	0.2738 (3)	0.4859 (2)	0.38862 (17)	0.0687 (9)
H3A	0.3267	0.4770	0.3506	0.082*
H3B	0.2603	0.4144	0.4080	0.082*
C4	0.1544 (3)	0.5325 (3)	0.36440 (19)	0.0818 (10)
H4A	0.1199	0.4846	0.3310	0.098*
H4B	0.0992	0.5376	0.4017	0.098*
C5	0.1745 (3)	0.6445 (3)	0.33458 (17)	0.0754 (9)
H5A	0.0987	0.6750	0.3204	0.090*
H5B	0.2256	0.6385	0.2956	0.090*
C6	0.2325 (2)	0.7196 (2)	0.38630 (15)	0.0636 (8)
H6A	0.1771	0.7307	0.4230	0.076*
H6B	0.2473	0.7900	0.3658	0.076*
C7	0.3973 (2)	0.75009 (19)	0.46978 (14)	0.0516 (6)
H7A	0.3362	0.7574	0.5039	0.062*
H7B	0.4663	0.7161	0.4904	0.062*
C8	0.4524 (2)	0.50733 (18)	0.46260 (13)	0.0429 (6)
H8A	0.4788	0.4578	0.4278	0.052*
H8B	0.5121	0.5641	0.4669	0.052*
C9	0.3553 (2)	0.9473 (2)	0.44790 (14)	0.0510 (6)
C10	0.5450 (2)	0.8844 (2)	0.42461 (14)	0.0543 (7)
C11	0.5473 (2)	1.0026 (2)	0.40424 (16)	0.0586 (7)
H11	0.6089	1.0429	0.4288	0.070*
C12	0.5566 (3)	1.0230 (3)	0.32838 (18)	0.0724 (9)
H12	0.6171	0.9793	0.3053	0.087*
C13	0.5667 (3)	1.1452 (3)	0.3173 (2)	0.0956 (13)
H13A	0.5866	1.1616	0.2711	0.115*
H13B	0.6269	1.1768	0.3463	0.115*
C14	0.4411 (3)	1.1879 (3)	0.3352 (2)	0.0903 (11)
H14A	0.4442	1.2381	0.3727	0.108*
H14B	0.4043	1.2241	0.2972	0.108*
C15	0.3741 (3)	1.0839 (2)	0.35359 (16)	0.0643 (8)
H15	0.2870	1.0896	0.3507	0.077*
C16	0.4211 (2)	1.0450 (2)	0.42160 (14)	0.0555 (7)
H16	0.4237	1.1043	0.4544	0.067*
C17	0.4291 (3)	1.0019 (3)	0.30617 (16)	0.0728 (9)
H17A	0.4158	1.0201	0.2595	0.087*
H17B	0.4033	0.9279	0.3151	0.087*
C18	0.4400 (2)	0.51847 (18)	0.58658 (12)	0.0404 (5)
H18A	0.3685	0.5629	0.5843	0.049*
H18B	0.5085	0.5668	0.5865	0.049*
C19	0.4391 (2)	0.4532 (2)	0.65033 (12)	0.0446 (6)
H19A	0.4380	0.5018	0.6886	0.054*
H19B	0.3681	0.4079	0.6521	0.054*
C20	0.5448 (2)	0.30604 (19)	0.59814 (12)	0.0417 (5)
H20A	0.4737	0.2611	0.6010	0.050*
H20B	0.6141	0.2589	0.6012	0.050*
C21	0.54609 (19)	0.36631 (17)	0.53267 (12)	0.0387 (5)
H21A	0.6213	0.4049	0.5282	0.046*
H21B	0.5407	0.3142	0.4963	0.046*
C22	0.5904 (2)	0.35074 (19)	0.71390 (12)	0.0396 (5)
C23	0.63088 (19)	0.42610 (19)	0.76474 (12)	0.0395 (5)
C24	0.6322 (2)	0.5409 (2)	0.76601 (13)	0.0473 (6)
H24	0.6003	0.5809	0.7307	0.057*
C25	0.6813 (2)	0.5925 (2)	0.82006 (15)	0.0597 (7)
H25	0.6816	0.6682	0.8215	0.072*
C26	0.7306 (3)	0.5342 (3)	0.87282 (15)	0.0638 (8)
H26	0.7618	0.5716	0.9093	0.077*
C27	0.7342 (3)	0.4226 (3)	0.87204 (14)	0.0601 (7)
H27	0.7692	0.3837	0.9068	0.072*
C28	0.6836 (2)	0.3692 (2)	0.81747 (12)	0.0467 (6)
H2A	0.3847 (16)	0.4111 (16)	0.5276 (12)	0.037 (6)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0766 (5)	0.0453 (3)	0.0561 (4)	−0.0030 (3)	−0.0137 (4)	0.0137 (3)
Cl1	0.0561 (4)	0.0614 (4)	0.0938 (6)	−0.0249 (3)	−0.0178 (4)	0.0066 (4)
N1	0.0479 (11)	0.0405 (11)	0.0569 (13)	0.0061 (9)	−0.0117 (10)	−0.0027 (10)
N2	0.0285 (9)	0.0358 (10)	0.0417 (11)	−0.0027 (8)	0.0012 (8)	−0.0007 (9)
N3	0.0380 (10)	0.0405 (11)	0.0432 (12)	0.0105 (8)	−0.0033 (9)	−0.0032 (8)
N4	0.0570 (12)	0.0400 (11)	0.0526 (13)	−0.0056 (9)	−0.0067 (10)	0.0059 (9)
O1	0.0633 (12)	0.0681 (12)	0.0673 (13)	0.0200 (10)	0.0118 (11)	0.0036 (10)
O2	0.0536 (11)	0.0732 (14)	0.0975 (17)	0.0233 (10)	−0.0105 (11)	0.0050 (12)
C1	0.0471 (13)	0.0446 (13)	0.0449 (14)	0.0025 (11)	−0.0076 (11)	0.0008 (11)
C2	0.0406 (12)	0.0459 (13)	0.0450 (14)	−0.0031 (11)	−0.0008 (11)	0.0026 (11)
C3	0.076 (2)	0.0525 (16)	0.077 (2)	−0.0086 (14)	−0.0293 (17)	0.0018 (14)
C4	0.073 (2)	0.082 (2)	0.091 (2)	−0.0179 (18)	−0.0384 (18)	0.0016 (19)
C5	0.0680 (19)	0.081 (2)	0.077 (2)	−0.0042 (17)	−0.0353 (17)	0.0109 (18)
C6	0.0590 (16)	0.0590 (17)	0.073 (2)	0.0048 (14)	−0.0211 (15)	0.0119 (15)
C7	0.0556 (14)	0.0452 (14)	0.0540 (16)	0.0078 (11)	−0.0112 (13)	0.0038 (12)
C8	0.0435 (13)	0.0404 (13)	0.0449 (15)	−0.0001 (10)	0.0051 (11)	0.0032 (11)
C9	0.0523 (15)	0.0498 (15)	0.0510 (16)	0.0121 (12)	−0.0094 (12)	−0.0058 (12)
C10	0.0453 (14)	0.0578 (17)	0.0598 (18)	0.0073 (13)	−0.0163 (13)	−0.0028 (13)
C11	0.0479 (14)	0.0548 (17)	0.073 (2)	−0.0038 (12)	−0.0193 (14)	0.0060 (14)
C12	0.0573 (17)	0.081 (2)	0.079 (2)	0.0114 (16)	0.0023 (16)	0.0167 (18)
C13	0.075 (2)	0.103 (3)	0.109 (3)	−0.016 (2)	−0.015 (2)	0.045 (2)
C14	0.104 (3)	0.073 (2)	0.094 (3)	0.009 (2)	−0.015 (2)	0.029 (2)
C15	0.0517 (15)	0.0691 (18)	0.072 (2)	0.0122 (15)	−0.0086 (15)	0.0186 (16)
C16	0.0628 (16)	0.0418 (14)	0.0618 (18)	0.0080 (12)	−0.0131 (14)	−0.0058 (13)
C17	0.071 (2)	0.090 (2)	0.058 (2)	−0.0015 (17)	−0.0110 (16)	0.0081 (17)
C18	0.0399 (12)	0.0355 (12)	0.0459 (14)	0.0080 (10)	−0.0045 (11)	−0.0074 (10)
C19	0.0405 (12)	0.0501 (14)	0.0433 (14)	0.0078 (11)	0.0016 (11)	−0.0080 (11)
C20	0.0405 (12)	0.0369 (12)	0.0477 (14)	0.0077 (10)	−0.0036 (11)	−0.0036 (10)
C21	0.0340 (11)	0.0353 (11)	0.0467 (14)	0.0041 (9)	−0.0013 (10)	−0.0067 (11)
C22	0.0360 (11)	0.0403 (12)	0.0425 (14)	−0.0020 (10)	0.0006 (10)	0.0016 (11)
C23	0.0355 (11)	0.0440 (13)	0.0389 (13)	0.0004 (10)	0.0052 (10)	0.0013 (10)
C24	0.0447 (13)	0.0444 (13)	0.0526 (16)	0.0072 (11)	−0.0003 (12)	−0.0017 (12)
C25	0.0617 (16)	0.0456 (14)	0.072 (2)	0.0017 (13)	0.0015 (15)	−0.0155 (13)
C26	0.0681 (19)	0.071 (2)	0.0529 (18)	0.0024 (16)	−0.0095 (15)	−0.0162 (15)
C27	0.0636 (17)	0.0725 (19)	0.0441 (16)	0.0036 (15)	−0.0081 (13)	0.0008 (14)
C28	0.0467 (13)	0.0503 (14)	0.0431 (14)	−0.0043 (11)	0.0011 (12)	0.0052 (11)

Geometric parameters (Å, º) top

S1—N4	1.677 (2)	C11—C12	1.539 (5)
S1—C28	1.731 (3)	C11—C16	1.546 (4)
Cl1—H2A	2.152 (16)	C11—H11	0.9800
N1—C9	1.378 (3)	C12—C17	1.518 (4)
N1—C10	1.386 (3)	C12—C13	1.519 (4)
N1—C7	1.462 (3)	C12—H12	0.9800
N2—C18	1.483 (3)	C13—C14	1.543 (5)
N2—C8	1.494 (3)	C13—H13A	0.9700
N2—C21	1.499 (3)	C13—H13B	0.9700
N2—H2A	0.804 (15)	C14—C15	1.526 (4)
N3—C22	1.386 (3)	C14—H14A	0.9700
N3—C20	1.451 (3)	C14—H14B	0.9700
N3—C19	1.466 (3)	C15—C17	1.512 (4)
N4—C22	1.304 (3)	C15—C16	1.533 (4)
O1—C9	1.212 (3)	C15—H15	0.9800
O2—C10	1.208 (3)	C16—H16	0.9800
C1—C2	1.528 (3)	C17—H17A	0.9700
C1—C7	1.529 (3)	C17—H17B	0.9700
C1—C6	1.537 (3)	C18—C19	1.505 (4)
C1—H1	0.9800	C18—H18A	0.9700
C2—C8	1.528 (3)	C18—H18B	0.9700
C2—C3	1.538 (4)	C19—H19A	0.9700
C2—H2	0.9800	C19—H19B	0.9700
C3—C4	1.533 (4)	C20—C21	1.502 (3)
C3—H3A	0.9700	C20—H20A	0.9700
C3—H3B	0.9700	C20—H20B	0.9700
C4—C5	1.513 (4)	C21—H21A	0.9700
C4—H4A	0.9700	C21—H21B	0.9700
C4—H4B	0.9700	C22—C23	1.446 (3)
C5—C6	1.530 (4)	C23—C28	1.395 (3)
C5—H5A	0.9700	C23—C24	1.409 (3)
C5—H5B	0.9700	C24—C25	1.367 (4)
C6—H6A	0.9700	C24—H24	0.9300
C6—H6B	0.9700	C25—C26	1.389 (4)
C7—H7A	0.9700	C25—H25	0.9300
C7—H7B	0.9700	C26—C27	1.369 (4)
C8—H8A	0.9700	C26—H26	0.9300
C8—H8B	0.9700	C27—C28	1.392 (4)
C9—C16	1.501 (4)	C27—H27	0.9300
C10—C11	1.507 (4)

N4—S1—C28	94.62 (11)	C13—C12—H12	114.9
C9—N1—C10	113.2 (2)	C11—C12—H12	114.9
C9—N1—C7	123.6 (2)	C12—C13—C14	103.5 (3)
C10—N1—C7	123.0 (2)	C12—C13—H13A	111.1
C18—N2—C8	113.15 (17)	C14—C13—H13A	111.1
C18—N2—C21	111.25 (17)	C12—C13—H13B	111.1
C8—N2—C21	110.59 (17)	C14—C13—H13B	111.1
C18—N2—H2A	106.1 (17)	H13A—C13—H13B	109.0
C8—N2—H2A	108.8 (17)	C15—C14—C13	102.7 (3)
C21—N2—H2A	106.6 (16)	C15—C14—H14A	111.2
C22—N3—C20	117.95 (18)	C13—C14—H14A	111.2
C22—N3—C19	119.43 (19)	C15—C14—H14B	111.2
C20—N3—C19	110.51 (18)	C13—C14—H14B	111.2
C22—N4—S1	110.51 (17)	H14A—C14—H14B	109.1
C2—C1—C7	110.4 (2)	C17—C15—C14	101.8 (3)
C2—C1—C6	110.8 (2)	C17—C15—C16	102.0 (2)
C7—C1—C6	110.3 (2)	C14—C15—C16	107.8 (3)
C2—C1—H1	108.4	C17—C15—H15	114.6
C7—C1—H1	108.4	C14—C15—H15	114.6
C6—C1—H1	108.4	C16—C15—H15	114.6
C1—C2—C8	112.67 (19)	C9—C16—C15	113.0 (2)
C1—C2—C3	111.3 (2)	C9—C16—C11	105.0 (2)
C8—C2—C3	109.3 (2)	C15—C16—C11	102.7 (2)
C1—C2—H2	107.8	C9—C16—H16	111.9
C8—C2—H2	107.8	C15—C16—H16	111.9
C3—C2—H2	107.8	C11—C16—H16	111.9
C4—C3—C2	112.5 (3)	C15—C17—C12	95.0 (3)
C4—C3—H3A	109.1	C15—C17—H17A	112.7
C2—C3—H3A	109.1	C12—C17—H17A	112.7
C4—C3—H3B	109.1	C15—C17—H17B	112.7
C2—C3—H3B	109.1	C12—C17—H17B	112.7
H3A—C3—H3B	107.8	H17A—C17—H17B	110.2
C5—C4—C3	109.5 (3)	N2—C18—C19	111.08 (18)
C5—C4—H4A	109.8	N2—C18—H18A	109.4
C3—C4—H4A	109.8	C19—C18—H18A	109.4
C5—C4—H4B	109.8	N2—C18—H18B	109.4
C3—C4—H4B	109.8	C19—C18—H18B	109.4
H4A—C4—H4B	108.2	H18A—C18—H18B	108.0
C4—C5—C6	110.1 (3)	N3—C19—C18	109.03 (19)
C4—C5—H5A	109.6	N3—C19—H19A	109.9
C6—C5—H5A	109.6	C18—C19—H19A	109.9
C4—C5—H5B	109.6	N3—C19—H19B	109.9
C6—C5—H5B	109.6	C18—C19—H19B	109.9
H5A—C5—H5B	108.1	H19A—C19—H19B	108.3
C5—C6—C1	113.6 (2)	N3—C20—C21	109.03 (18)
C5—C6—H6A	108.9	N3—C20—H20A	109.9
C1—C6—H6A	108.9	C21—C20—H20A	109.9
C5—C6—H6B	108.9	N3—C20—H20B	109.9
C1—C6—H6B	108.9	C21—C20—H20B	109.9
H6A—C6—H6B	107.7	H20A—C20—H20B	108.3
N1—C7—C1	113.9 (2)	N2—C21—C20	112.22 (18)
N1—C7—H7A	108.8	N2—C21—H21A	109.2
C1—C7—H7A	108.8	C20—C21—H21A	109.2
N1—C7—H7B	108.8	N2—C21—H21B	109.2
C1—C7—H7B	108.8	C20—C21—H21B	109.2
H7A—C7—H7B	107.7	H21A—C21—H21B	107.9
N2—C8—C2	114.13 (19)	N4—C22—N3	120.5 (2)
N2—C8—H8A	108.7	N4—C22—C23	116.2 (2)
C2—C8—H8A	108.7	N3—C22—C23	122.9 (2)
N2—C8—H8B	108.7	C28—C23—C24	118.8 (2)
C2—C8—H8B	108.7	C28—C23—C22	110.1 (2)
H8A—C8—H8B	107.6	C24—C23—C22	130.9 (2)
O1—C9—N1	123.8 (3)	C25—C24—C23	118.8 (2)
O1—C9—C16	127.5 (2)	C25—C24—H24	120.6
N1—C9—C16	108.7 (2)	C23—C24—H24	120.6
O2—C10—N1	123.8 (3)	C24—C25—C26	121.4 (2)
O2—C10—C11	127.6 (3)	C24—C25—H25	119.3
N1—C10—C11	108.6 (2)	C26—C25—H25	119.3
C10—C11—C12	115.1 (3)	C27—C26—C25	121.2 (3)
C10—C11—C16	104.3 (2)	C27—C26—H26	119.4
C12—C11—C16	103.2 (2)	C25—C26—H26	119.4
C10—C11—H11	111.2	C26—C27—C28	117.9 (3)
C12—C11—H11	111.2	C26—C27—H27	121.1
C16—C11—H11	111.2	C28—C27—H27	121.1
C17—C12—C13	101.3 (3)	C27—C28—C23	121.9 (2)
C17—C12—C11	101.3 (2)	C27—C28—S1	129.4 (2)
C13—C12—C11	108.0 (3)	C23—C28—S1	108.56 (18)
C17—C12—H12	114.9

C28—S1—N4—C22	1.39 (19)	C17—C15—C16—C9	−77.6 (3)
C7—C1—C2—C8	−63.5 (3)	C14—C15—C16—C9	175.6 (3)
C6—C1—C2—C8	173.9 (2)	C17—C15—C16—C11	34.9 (3)
C7—C1—C2—C3	173.3 (2)	C14—C15—C16—C11	−71.8 (3)
C6—C1—C2—C3	50.7 (3)	C10—C11—C16—C9	−2.1 (3)
C1—C2—C3—C4	−55.1 (3)	C12—C11—C16—C9	118.5 (2)
C8—C2—C3—C4	179.9 (3)	C10—C11—C16—C15	−120.4 (2)
C2—C3—C4—C5	58.4 (4)	C12—C11—C16—C15	0.2 (3)
C3—C4—C5—C6	−57.7 (4)	C14—C15—C17—C12	55.5 (3)
C4—C5—C6—C1	56.5 (4)	C16—C15—C17—C12	−55.8 (3)
C2—C1—C6—C5	−52.7 (3)	C13—C12—C17—C15	−55.7 (3)
C7—C1—C6—C5	−175.3 (2)	C11—C12—C17—C15	55.5 (3)
C9—N1—C7—C1	94.0 (3)	C8—N2—C18—C19	−177.22 (19)
C10—N1—C7—C1	−90.2 (3)	C21—N2—C18—C19	−52.0 (2)
C2—C1—C7—N1	171.9 (2)	C22—N3—C19—C18	154.8 (2)
C6—C1—C7—N1	−65.3 (3)	C20—N3—C19—C18	−63.5 (3)
C18—N2—C8—C2	−75.0 (2)	N2—C18—C19—N3	57.8 (2)
C21—N2—C8—C2	159.46 (19)	C22—N3—C20—C21	−155.6 (2)
C1—C2—C8—N2	136.8 (2)	C19—N3—C20—C21	62.0 (2)
C3—C2—C8—N2	−98.9 (3)	C18—N2—C21—C20	51.2 (2)
C10—N1—C9—O1	−179.0 (3)	C8—N2—C21—C20	177.88 (18)
C7—N1—C9—O1	−2.8 (4)	N3—C20—C21—N2	−55.6 (2)
C10—N1—C9—C16	2.6 (3)	S1—N4—C22—N3	172.05 (17)
C7—N1—C9—C16	178.8 (2)	S1—N4—C22—C23	−1.0 (3)
C9—N1—C10—O2	176.6 (3)	C20—N3—C22—N4	−12.3 (3)
C7—N1—C10—O2	0.4 (4)	C19—N3—C22—N4	126.7 (2)
C9—N1—C10—C11	−4.1 (3)	C20—N3—C22—C23	160.2 (2)
C7—N1—C10—C11	179.8 (2)	C19—N3—C22—C23	−60.7 (3)
O2—C10—C11—C12	70.7 (4)	N4—C22—C23—C28	0.0 (3)
N1—C10—C11—C12	−108.6 (3)	N3—C22—C23—C28	−172.9 (2)
O2—C10—C11—C16	−177.0 (3)	N4—C22—C23—C24	174.9 (2)
N1—C10—C11—C16	3.7 (3)	N3—C22—C23—C24	2.1 (4)
C10—C11—C12—C17	78.0 (3)	C28—C23—C24—C25	−2.4 (4)
C16—C11—C12—C17	−35.0 (3)	C22—C23—C24—C25	−177.0 (2)
C10—C11—C12—C13	−176.0 (2)	C23—C24—C25—C26	0.8 (4)
C16—C11—C12—C13	71.0 (3)	C24—C25—C26—C27	1.3 (4)
C17—C12—C13—C14	35.3 (4)	C25—C26—C27—C28	−1.8 (4)
C11—C12—C13—C14	−70.7 (3)	C26—C27—C28—C23	0.1 (4)
C12—C13—C14—C15	−0.6 (4)	C26—C27—C28—S1	175.9 (2)
C13—C14—C15—C17	−34.5 (3)	C24—C23—C28—C27	1.9 (4)
C13—C14—C15—C16	72.4 (3)	C22—C23—C28—C27	177.6 (2)
O1—C9—C16—C15	−67.3 (4)	C24—C23—C28—S1	−174.64 (18)
N1—C9—C16—C15	111.0 (3)	C22—C23—C28—S1	1.0 (2)
O1—C9—C16—C11	−178.5 (3)	N4—S1—C28—C27	−177.6 (2)
N1—C9—C16—C11	−0.1 (3)	N4—S1—C28—C23	−1.39 (19)

Hydrogen-bond geometry (Å, º) top

Cg is the centroid of the S1/ N4/C22/C23/C28 ring.

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···Cl1	0.80 (2)	2.15 (2)	2.9426 (19)	168 (2)
C21—H21A···O1ⁱ	0.97	2.38	3.289 (3)	156
C5—H5A···Cgⁱⁱ	0.97	2.89	3.802 (4)	157

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

Experimental details

Crystal data
Chemical formula	C₂₈H₃₇N₄O₂S⁺·Cl⁻
M_r	529.13
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	293
a, b, c (Å)	11.2039 (10), 12.2665 (11), 19.9774 (18)
V (Å³)	2745.5 (4)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.25
Crystal size (mm)	0.22 × 0.12 × 0.10

Data collection
Diffractometer	Bruker SMART CCD area-detector diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2000)
T_min, T_max	0.452, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	15020, 5384, 4649
R_int	0.028
(sin θ/λ)_max (Å⁻¹)	0.617

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.047, 0.108, 1.10
No. of reflections	5384
No. of parameters	329
No. of restraints	1
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.24, −0.14
Absolute structure	Flack (1983), 2338 Friedel pairs
Absolute structure parameter	0.03 (6)

Computer programs: SMART (Bruker, 2000), SAINT (Bruker, 2000), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

Cg is the centroid of the S1/ N4/C22/C23/C28 ring.

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···Cl1	0.804 (15)	2.152 (16)	2.9426 (19)	168 (2)
C21—H21A···O1ⁱ	0.97	2.38	3.289 (3)	156
C5—H5A···Cgⁱⁱ	0.97	2.89	3.802 (4)	157

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

Acknowledgements

The authors thank the Shanghai Institute of Organic Chemistry for providing the infrastructure.

References

Bruker (2000). SADABS, SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Flack, H. D. (1983). Acta Cryst. A39, 876–881. CrossRef CAS Web of Science IUCr Journals Google Scholar
Ishibashi, T., Horisawa, T., Yabuuchi, K., Tagashira, R. & Ohno, Y. (2002). Soc. Neurosci. Abstr. 894, 7. Google Scholar
Ishiyama, T., Matsumoto, Y., Tokuda, K., Horisawa, T., Tagashira, R., Toma, S. & Ohno, Y. (2003). Soc. Neurosci. Abstr. 835, 22. Google Scholar
Ohno, Y., Ishida, K., Ishibashi, T., Tojima, R., Yasui, J. & Nakamura, M. (1997). Int. Acad. Biomed. Drug Res. 11, 287–287. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar

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Volume 68| Part 5| May 2012| Page o1357

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