A new solvate of epalerstat, a drug for diabetic neuropathy

Putra, O.D.; Umeda, D.; Fukuzawa, K.; Gunji, M.; Yonemochi, E.

doi:10.1107/S2056989017010751

research communications

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 73| Part 8| August 2017| Pages 1264-1267

https://doi.org/10.1107/S2056989017010751

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A new solvate of epalerstat, a drug for diabetic neuropathy

Okky Dwichandra Putra,^a Daiki Umeda,^a Kaori Fukuzawa,^a Mihoko Gunji ^a and Etsuo Yonemochi ^a ^*

^aSchool of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41, Ebara, Shinagawa, Tokyo 145-8501, Japan
^*Correspondence e-mail: e-yonemochi@hoshi.ac.jp

Edited by H. Stoeckli-Evans, University of Neuchâtel, Switzerland (Received 20 July 2017; accepted 21 July 2017; online 28 July 2017)

Epalerstat {systematic name: (5Z)-5-[(2E)-2-methyl-3-phenylprop-2-en-1-ylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidine-3-acetic acid} crystallized as an acetone monosolvate, C₁₅H₁₃NO₃S₂·C₃H₆O. In the epalerstat molecule, the methylpropylenediene moiety is inclined to the phenyl ring and the five-membered rhodamine ring by 21.4 (4) and 4.7 (4)°, respectively. In addition, the acetic acid moiety is found to be almost normal to the rhodamine ring, making a dihedral angle of 85.1 (2)°. In the crystal, a pair of O—H⋯O hydrogen bonds between the carboxylic acid groups of epalerstat molecules form inversion dimers with an R₂²(8) loop. The dimers are linked by pairs of C—H⋯O hydrogen bonds, enclosing R₂²(20) loops, forming chains propagating along the [101] direction. In addition, the acetone molecules are linked to the chain by a C—H⋯O hydrogen bond. Epalerstat acetone monosolvate was found to be isotypic with epalerstat tertrahydrofuran solvate [Umeda et al. (2017 ). Acta Cryst. E73, 941–944].

Keywords: crystal structure; epalerstat; acetone; monosolvate; isotypic; hydrogen bonding.

CCDC reference: 1563705

1. Chemical context

Investigation of solid forms of pharmaceuticals has attracted a great deal of attention as different crystal forms may imply different physicochemical properties (Putra et al., 2016a ,b ). Moreover, pharmaceutical processing stages during manufacturing, such as crystallization, can lead to the unexpected occurrence of new crystalline phases (Putra et al., 2016c ). One of the important classes of pharmaceutical solids that can occur during crystallization is solvates. Solvates are defined as multi-component crystalline systems in which solvent molecules are included within the crystal structure in either a stoichiometric or non-stoichiometric manner (Griesser, 2006 ). It has been estimated statistically that around 33% of organic compounds have the ability to form solvates with organic solvents (Clarke et al., 2010 ).

Herein, we report on the crystal structure of a new solvate form of epalerstat, namely epalerstat acetone monosolvate. Epalerstat [systematic name: (5Z)-5-[(2E)-2-methyl-3-phenylprop-2-en-1-ylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidine-3-acetic acid), is an aldose reductase inhibitor and is used for the treatment of diabetic neuropathy, a complication symptom in diabetes mellitus (Miyamoto, 2002 ). Pharmacologically, epalerstat acts to inhibit the synthesis of sorbitol from glucose (Ramirez & Borja, 2008 ). The abundant occurrences of solvates in epalerstat itself is not surprising because of the imbalance between the hydrogen-bond donors and acceptors in its molecular structure. Previously, the crystal structures of the methanol mono- and disolvate (Igarashi et al., 2015 ; Nagase et al., 2016 ), the ethanol monosolvate (Ishida et al., 1989 , 1990 ), the dimethylformamide monosolvate (Putra et al., 2017 ), the dimethylsulfoxide disolvate (Putra et al., 2017) and the tetrahydrofuran monosolvate (Umeda et al., 2017) have been reported.

2. Structural commentary

The molecular structure of epalerstat acetone monosolvate is illustrated in Fig. 1. The values of the bond distances, bond angles and dihedral angles are normal according the Mogul geometry check within the CSD software (Bruno et al., 2004 ; Groom et al., 2016 ). The mean plane of the methylpropylenediene (C7–C10) moiety is inclined to the phenyl ring (C1–C6) and the five-membered rhodamine ring (S1/S2/O1/N1/C11–C13) by 21.4 (4) and 4.7 (4)°, respectively. The mean plane of the acetic acid moiety (O2/O3/C14/C15) is almost normal to the rhodamine ring, making a dihedral angle of 85.1 (2) °.

Figure 1
The molecular structure of epalerstat acetone monosolvate, with the atom labelling and displacement ellipsoids drawn at the 50% probability level.

3. Supramolecular features

In the crystal, the epalerstat molecule is connected to two adjacent epalerstat molecules and one solvent molecule via both conventional and non-conventional hydrogen bonds. The details of the hydrogen bonds and hydrogen bonding architecture are listed and presented in Table 1 and Fig. 2, respectively. A pair of O3—H3A⋯O2ⁱⁱ hydrogen bonds is observed between two carboxylic acid moieties forming an inversion dimer with an R₂²(8) loop. This dimer is linked to adjacent dimers by a pair of C6—H6⋯O1ⁱⁱ hydrogen bonds, which enclose R₂²(20) loops, and form chains along direction [101]. In addition, acetone molecules are linked to the chain by a C1—H1⋯O4ⁱⁱⁱ hydrogen bond (Table 1 and Fig. 2).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3A⋯O2ⁱ	0.91 (3)	1.75 (3)	2.645 (2)	171 (3)
C6—H6⋯O1ⁱⁱ	0.95	2.50	3.440 (3)	168
C1—H1⋯O4ⁱⁱⁱ	0.95	2.58	3.525 (3)	171
Symmetry codes: (i) -x, -y, -z; (ii) -x-1, -y, -z+1; (iii) -x, -y+1, -z+1.

Figure 2
A view along the b axis of the crystal packing of the title compound. Blue and orange dashed lines represent O—H⋯O and C—H⋯O hydrogen bonds, respectively. Only H atoms involved in these interactions have been included.

3.1. Discussion

Interestingly, the new solvate reported here is isotypic with epalerstat tetrahydrofuran monosolvate (Umeda et al., 2017). Both solvates crystallize in the triclinic system with the same space group, P $[\overline{1}]$ . As illustrated in Fig. 3, they have a similar molecular arrangement and the solvent molecules are located in similar pockets in the unit cell. The unit cell similarity index (Π) and the mean elongation (∊) values were calculated (Fábián & Kálmán, 1999 ) and found to be Π = 0.0016 and ∊ = 0.0005. As the Π and ∊ values are nearly zero, epalerstat acetone monosolvate and tetrahydrofuran monosolvate have isostructural crystals. The solvent-occupied spaces, in which the solvent molecules were deleted from the crystal structure, and the voids were calculated using the contact surface method with probe radius and approximate grid spacing set equal to 1.2 and 0.7 Å, respectively (Putra et al., 2016d ; Macrae et al., 2008 ). The solvent occupied spaces for the acetone and tetrahydrofuran solvates are 199.86 and 221.89 Å³, respectively. As expected, the larger occupied space in epalerstat tetrahydrofuran solvate corresponds to the larger solvent molecule. Interestingly, both solvents occupy nearly the same percentage of the total volume of the unit cell; the acetone and tetrahydrofuran molecules occupy 22.2 and 23.8%, respectively.

Figure 3
The packing view along the b axis of (a) epalerstat acetone monosolvate and (b) epalerstat tetrahydrofuran monosolvate shows the isostructurality between the two solvates. H atoms have been omitted for clarity, and the epalerstat molecules and the solvent molecules are drawn as capped sticks and spacefill models, respectively.

4. Database survey

A search of the Cambridge Structural Database (CSD, V5.38, last update July 2017; Groom et al., 2016) for epalerstat yielded 16 hits. They include the ethanol monosolvate (Ishida et al., 1989, 1990), the methanol monosolvate (Igarashi et al., 2015), the methanol disolvate (Nagase et al., 2016), the dimethylformamide monosolvate (Putra et al., 2017), the dimethylsulfoxide disolvate (Putra et al., 2017), the tetrahydrofuran monosolvate (Umeda et al., 2017), Form I: triclinic, P $[\overline{1}]$ (Igarashi et al., 2013 ; Swapna et al., 2016 ), Form II: monoclinic, C2/c (Swapna et al., 2016), Form III: monoclinic, P2₁/n (Swapna et al., 2016), the co-crystal with caffeine (Putra et al., 2017), a series of salt co-crystals with cytosine (Swapna & Nangia, 2017 ) and the Z,Z isomer (Swapna et al., 2016).

5. Synthesis and crystallization

Epalerstat Form I (700 mg) was dissolved in 10 ml acetone and the clear solution was then kept for three days at room temperature. Epalerstat acetone monosolvate appeared concomitantly with epalerstat Form I and they could be distinguished visually based on their crystal habit. In this case, the title compound, epalerstat acetone monosolvate, and Form I appeared as yellow blocks and orange needle-like crystals, respectively.

6. Refinement details

Crystal data, data collection and structure refinement details are summarized in Table 2. The hydrogen atom attached to an oxygen atom was located in a difference-Fourier map and freely refined. The C-bound H atoms were included in calculated positions and treated using riding model: C—H = 0.9–1.0 Å with U_iso(H) = 1.5U_iso(C-methyl) and 1.2U_iso(C) for other H atoms. Initially the site occupancy factor of the acetone molecule was refined and determined to be 1.005 (4). In the final cycles of refinement the occupancy of the acetone molecule was fixed at 1.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₅H₁₃NO₃S₂·C₃H₆O
M_r	377.46
Crystal system, space group	Triclinic, P $[\overline{1}]$
Temperature (K)	93
a, b, c (Å)	7.9623 (1), 8.1806 (2), 15.6919 (3)
α, β, γ (°)	97.852 (7), 99.837 (7), 113.206 (8)
V (Å³)	901.83 (6)
Z	2
Radiation type	Cu Kα
μ (mm⁻¹)	2.87
Crystal size (mm)	0.35 × 0.24 × 0.10

Data collection
Diffractometer	Rigaku R-AXIS RAPID II
Absorption correction	Multi-scan (ABSCOR; Higashi, 1995 )
T_min, T_max	0.378, 0.750
No. of measured, independent and observed [I > 2σ(I)] reflections	10593, 3235, 2790
R_int	0.045
(sin θ/λ)_max (Å⁻¹)	0.602

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.050, 0.137, 1.11
No. of reflections	3235
No. of parameters	233
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.73, −0.30
Computer programs: PROCESS-AUTO (Rigaku, 1998 ), SHELXS2014 (Sheldrick, 2008 ), Mercury (Macrae et al., 2008), SHELXL2016 (Sheldrick, 2015 ) and PLATON (Spek, 2009 ).

Supporting information

CCDC reference: 1563705

Crystal structure: contains datablocks I, Global. DOI: https://doi.org/10.1107/S2056989017010751/su5385sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989017010751/su5385Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989017010751/su5385Isup3.cml

checkCIF report

Computing details top

Data collection: PROCESS-AUTO (Rigaku, 1998); cell refinement: PROCESS-AUTO (Rigaku, 1998); data reduction: PROCESS-AUTO (Rigaku, 1998); program(s) used to solve structure: SHELXS2014 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2016 (Sheldrick, 2015); molecular graphics: Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL2016 (Sheldrick, 2015) and PLATON (Spek, 2009).

(5Z)-5-[(2E)-2-Methyl-3-phenylprop-2-en-1-ylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidine-3-acetic acid acetone monosolvate top

Crystal data top

C₁₅H₁₃NO₃S₂·C₃H₆O	Z = 2
M_r = 377.46	F(000) = 396
Triclinic, P1	D_x = 1.390 Mg m⁻³
a = 7.9623 (1) Å	Cu Kα radiation, λ = 1.54187 Å
b = 8.1806 (2) Å	Cell parameters from 10593 reflections
c = 15.6919 (3) Å	θ = 5.9–68.2°
α = 97.852 (7)°	µ = 2.87 mm⁻¹
β = 99.837 (7)°	T = 93 K
γ = 113.206 (8)°	Block, yellow
V = 901.83 (6) Å³	0.35 × 0.24 × 0.10 mm

Data collection top

Rigaku R-AXIS RAPID II diffractometer	3235 independent reflections
Radiation source: rotating anode X-ray, RIGAKU	2790 reflections with I > 2σ(I)
Detector resolution: 10.0 pixels mm^-1	R_int = 0.045
ω scan	θ_max = 68.2°, θ_min = 5.9°
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)	h = −9→9
T_min = 0.378, T_max = 0.750	k = −9→9
10593 measured reflections	l = −18→18

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.050	Hydrogen site location: mixed
wR(F²) = 0.137	H atoms treated by a mixture of independent and constrained refinement
S = 1.11	w = 1/[σ²(F_o²) + (0.0886P)²] where P = (F_o² + 2F_c²)/3
3235 reflections	(Δ/σ)_max < 0.001
233 parameters	Δρ_max = 0.73 e Å⁻³
0 restraints	Δρ_min = −0.30 e Å⁻³

Special details top

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 esds are taken into account in the estimation of distances, angles and torsion angles

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
S1	0.32326 (7)	0.22776 (7)	0.40775 (3)	0.0232 (2)
S2	0.53005 (7)	0.15013 (8)	0.27814 (4)	0.0290 (2)
O1	−0.15383 (19)	−0.1417 (2)	0.26694 (9)	0.0270 (5)
O2	0.0245 (2)	0.0465 (2)	0.10793 (9)	0.0257 (5)
O3	0.0821 (2)	−0.1687 (2)	0.02943 (10)	0.0304 (5)
N1	0.1578 (2)	−0.0247 (2)	0.26497 (11)	0.0214 (5)
C1	−0.2491 (3)	0.5295 (3)	0.76805 (14)	0.0256 (7)
C2	−0.0768 (3)	0.6025 (3)	0.74641 (14)	0.0252 (7)
C3	−0.0449 (3)	0.5163 (3)	0.67266 (13)	0.0232 (6)
C4	−0.1877 (3)	0.3532 (3)	0.61713 (14)	0.0214 (6)
O4	0.3463 (2)	0.3068 (2)	0.03521 (11)	0.0438 (6)
C5	−0.3632 (3)	0.2835 (3)	0.63920 (14)	0.0235 (6)
C6	−0.3931 (3)	0.3700 (3)	0.71326 (14)	0.0252 (7)
C7	−0.1685 (3)	0.2516 (3)	0.53833 (13)	0.0216 (6)
C8	−0.0128 (3)	0.2508 (3)	0.51367 (13)	0.0215 (6)
C9	0.1858 (3)	0.3596 (3)	0.56879 (14)	0.0242 (6)
C10	−0.0467 (3)	0.1284 (3)	0.43048 (13)	0.0218 (6)
C11	0.0769 (3)	0.1067 (3)	0.38588 (13)	0.0211 (6)
C12	0.0075 (3)	−0.0322 (3)	0.30199 (13)	0.0220 (7)
C13	0.3343 (3)	0.1078 (3)	0.30963 (14)	0.0226 (6)
C14	0.1251 (3)	−0.1486 (3)	0.18203 (13)	0.0234 (6)
C15	0.0718 (3)	−0.0778 (3)	0.10282 (14)	0.0230 (6)
C16	0.6721 (4)	0.3855 (4)	0.08636 (16)	0.0463 (9)
C17	0.4865 (3)	0.2987 (3)	0.01874 (15)	0.0306 (7)
C18	0.4837 (4)	0.2023 (4)	−0.07037 (16)	0.0397 (8)
H1	−0.26853	0.58768	0.81968	0.0310*
H2	0.02089	0.71326	0.78271	0.0300*
H3	0.07467	0.56789	0.65942	0.0280*
H3A	0.034 (4)	−0.130 (4)	−0.016 (2)	0.066 (10)*
H5	−0.46298	0.17474	0.60237	0.0280*
H6	−0.51254	0.32025	0.72678	0.0300*
H7	−0.28463	0.17230	0.49709	0.0260*
H9A	0.24324	0.47371	0.54951	0.0360*
H9B	0.25903	0.28868	0.56141	0.0360*
H9C	0.18490	0.38731	0.63143	0.0360*
H10	−0.17563	0.05124	0.40288	0.0260*
H14A	0.02271	−0.26889	0.17941	0.0280*
H14B	0.24067	−0.16584	0.17988	0.0280*
H16A	0.66246	0.45979	0.13819	0.0690*
H16B	0.76964	0.46315	0.06051	0.0690*
H16C	0.70570	0.29014	0.10460	0.0690*
H18A	0.35396	0.14160	−0.10715	0.0590*
H18B	0.53261	0.11105	−0.06269	0.0590*
H18C	0.56266	0.29111	−0.09945	0.0590*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0185 (3)	0.0257 (3)	0.0223 (3)	0.0072 (2)	0.0049 (2)	0.0033 (2)
S2	0.0207 (3)	0.0327 (4)	0.0313 (3)	0.0088 (3)	0.0094 (2)	0.0041 (3)
O1	0.0193 (8)	0.0290 (9)	0.0267 (8)	0.0060 (7)	0.0039 (6)	0.0033 (7)
O2	0.0287 (8)	0.0273 (9)	0.0227 (8)	0.0147 (7)	0.0057 (6)	0.0029 (6)
O3	0.0355 (9)	0.0386 (10)	0.0221 (8)	0.0233 (8)	0.0047 (7)	0.0020 (7)
N1	0.0205 (9)	0.0223 (10)	0.0204 (9)	0.0082 (8)	0.0056 (7)	0.0036 (7)
C1	0.0304 (12)	0.0290 (13)	0.0238 (11)	0.0168 (10)	0.0099 (9)	0.0091 (9)
C2	0.0251 (11)	0.0242 (12)	0.0267 (11)	0.0115 (9)	0.0049 (9)	0.0056 (9)
C3	0.0196 (10)	0.0233 (12)	0.0266 (11)	0.0081 (9)	0.0064 (9)	0.0074 (9)
C4	0.0221 (11)	0.0232 (11)	0.0232 (11)	0.0123 (9)	0.0066 (9)	0.0091 (9)
O4	0.0331 (10)	0.0508 (11)	0.0447 (11)	0.0144 (8)	0.0180 (8)	0.0027 (9)
C5	0.0192 (10)	0.0248 (12)	0.0268 (11)	0.0099 (9)	0.0038 (9)	0.0073 (9)
C6	0.0205 (11)	0.0300 (13)	0.0281 (11)	0.0119 (9)	0.0082 (9)	0.0096 (10)
C7	0.0208 (11)	0.0199 (11)	0.0238 (11)	0.0083 (9)	0.0037 (9)	0.0073 (9)
C8	0.0231 (11)	0.0223 (11)	0.0217 (10)	0.0106 (9)	0.0074 (9)	0.0079 (9)
C9	0.0213 (11)	0.0293 (12)	0.0227 (10)	0.0122 (9)	0.0054 (9)	0.0040 (9)
C10	0.0205 (10)	0.0220 (11)	0.0232 (11)	0.0085 (9)	0.0052 (9)	0.0081 (9)
C11	0.0211 (11)	0.0212 (11)	0.0212 (10)	0.0085 (9)	0.0051 (8)	0.0077 (9)
C12	0.0216 (11)	0.0236 (12)	0.0226 (11)	0.0101 (9)	0.0056 (9)	0.0091 (9)
C13	0.0197 (11)	0.0227 (11)	0.0260 (11)	0.0089 (9)	0.0051 (9)	0.0082 (9)
C14	0.0251 (11)	0.0215 (11)	0.0230 (11)	0.0095 (9)	0.0084 (9)	0.0012 (9)
C15	0.0146 (10)	0.0261 (12)	0.0234 (11)	0.0058 (9)	0.0040 (8)	0.0000 (9)
C16	0.0394 (15)	0.0540 (18)	0.0356 (14)	0.0151 (13)	0.0027 (12)	0.0022 (13)
C17	0.0282 (13)	0.0318 (13)	0.0308 (12)	0.0100 (10)	0.0100 (10)	0.0089 (10)
C18	0.0330 (13)	0.0541 (17)	0.0317 (13)	0.0211 (12)	0.0078 (11)	0.0016 (12)

Geometric parameters (Å, º) top

S1—C11	1.759 (3)	C11—C12	1.476 (3)
S1—C13	1.744 (2)	C14—C15	1.507 (3)
S2—C13	1.636 (3)	C1—H1	0.9500
O1—C12	1.213 (3)	C2—H2	0.9500
O2—C15	1.213 (3)	C3—H3	0.9500
O3—C15	1.316 (3)	C5—H5	0.9500
N1—C12	1.401 (3)	C6—H6	0.9500
N1—C13	1.377 (3)	C7—H7	0.9500
N1—C14	1.451 (3)	C9—H9B	0.9800
O3—H3A	0.91 (3)	C9—H9C	0.9800
C1—C6	1.391 (3)	C9—H9A	0.9800
C1—C2	1.387 (4)	C10—H10	0.9500
C2—C3	1.386 (3)	C14—H14A	0.9900
C3—C4	1.407 (3)	C14—H14B	0.9900
C4—C5	1.410 (4)	C16—C17	1.499 (4)
C4—C7	1.459 (3)	C17—C18	1.501 (3)
O4—C17	1.212 (3)	C16—H16A	0.9800
C5—C6	1.382 (3)	C16—H16B	0.9800
C7—C8	1.363 (4)	C16—H16C	0.9800
C8—C10	1.445 (3)	C18—H18A	0.9800
C8—C9	1.501 (3)	C18—H18B	0.9800
C10—C11	1.352 (3)	C18—H18C	0.9800

C11—S1—C13	93.02 (11)	C4—C3—H3	120.00
C12—N1—C13	116.89 (18)	C4—C5—H5	119.00
C12—N1—C14	120.69 (18)	C6—C5—H5	119.00
C13—N1—C14	122.41 (19)	C1—C6—H6	120.00
C15—O3—H3A	107 (2)	C5—C6—H6	120.00
C2—C1—C6	119.2 (2)	C4—C7—H7	114.00
C1—C2—C3	121.0 (2)	C8—C7—H7	114.00
C2—C3—C4	120.7 (2)	C8—C9—H9A	109.00
C3—C4—C5	117.4 (2)	C8—C9—H9B	109.00
C5—C4—C7	117.6 (2)	C8—C9—H9C	109.00
C3—C4—C7	125.1 (2)	H9A—C9—H9B	109.00
C4—C5—C6	121.4 (2)	H9A—C9—H9C	109.00
C1—C6—C5	120.3 (2)	H9B—C9—H9C	109.00
C4—C7—C8	131.1 (2)	C8—C10—H10	115.00
C7—C8—C9	124.49 (19)	C11—C10—H10	115.00
C7—C8—C10	116.2 (2)	N1—C14—H14A	109.00
C9—C8—C10	119.2 (2)	N1—C14—H14B	109.00
C8—C10—C11	129.9 (2)	C15—C14—H14A	109.00
S1—C11—C12	109.41 (17)	C15—C14—H14B	109.00
C10—C11—C12	119.9 (2)	H14A—C14—H14B	108.00
S1—C11—C10	130.59 (17)	O4—C17—C16	121.6 (2)
O1—C12—C11	127.7 (2)	O4—C17—C18	121.9 (2)
N1—C12—C11	110.3 (2)	C16—C17—C18	116.5 (2)
O1—C12—N1	122.00 (19)	C17—C16—H16A	110.00
S1—C13—N1	110.27 (17)	C17—C16—H16B	109.00
S2—C13—N1	126.30 (17)	C17—C16—H16C	109.00
S1—C13—S2	123.43 (14)	H16A—C16—H16B	109.00
N1—C14—C15	111.81 (19)	H16A—C16—H16C	109.00
O2—C15—C14	123.1 (2)	H16B—C16—H16C	109.00
O3—C15—C14	111.3 (2)	C17—C18—H18A	109.00
O2—C15—O3	125.6 (2)	C17—C18—H18B	109.00
C2—C1—H1	120.00	C17—C18—H18C	110.00
C6—C1—H1	120.00	H18A—C18—H18B	109.00
C1—C2—H2	120.00	H18A—C18—H18C	109.00
C3—C2—H2	119.00	H18B—C18—H18C	109.00
C2—C3—H3	120.00

C13—S1—C11—C10	−175.1 (2)	C2—C3—C4—C7	−179.8 (2)
C13—S1—C11—C12	1.91 (17)	C7—C4—C5—C6	179.3 (2)
C11—S1—C13—S2	177.60 (16)	C5—C4—C7—C8	−159.0 (2)
C11—S1—C13—N1	−2.90 (17)	C3—C4—C5—C6	−1.1 (3)
C14—N1—C13—S2	1.0 (3)	C3—C4—C7—C8	21.4 (4)
C14—N1—C12—C11	179.93 (18)	C4—C5—C6—C1	0.1 (4)
C12—N1—C13—S1	3.3 (2)	C4—C7—C8—C9	2.0 (4)
C13—N1—C12—O1	178.6 (2)	C4—C7—C8—C10	178.8 (2)
C14—N1—C12—O1	0.4 (3)	C9—C8—C10—C11	−8.4 (4)
C13—N1—C12—C11	−1.8 (3)	C7—C8—C10—C11	174.7 (2)
C13—N1—C14—C15	−93.1 (3)	C8—C10—C11—C12	178.6 (2)
C14—N1—C13—S1	−178.51 (15)	C8—C10—C11—S1	−4.7 (4)
C12—N1—C13—S2	−177.26 (17)	C10—C11—C12—O1	−3.6 (4)
C12—N1—C14—C15	85.1 (2)	C10—C11—C12—N1	176.9 (2)
C2—C1—C6—C5	1.3 (3)	S1—C11—C12—N1	−0.5 (2)
C6—C1—C2—C3	−1.8 (4)	S1—C11—C12—O1	179.0 (2)
C1—C2—C3—C4	0.8 (4)	N1—C14—C15—O2	−14.2 (3)
C2—C3—C4—C5	0.7 (3)	N1—C14—C15—O3	166.38 (19)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3A···O2ⁱ	0.91 (3)	1.75 (3)	2.645 (2)	171 (3)
C6—H6···O1ⁱⁱ	0.95	2.50	3.440 (3)	168
C1—H1···O4ⁱⁱⁱ	0.95	2.58	3.525 (3)	171

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

Acknowledgements

We wish to thank for Professor Hiromasa Nagase (Hoshi University) for technical support during the single-crystal X-ray measurements.

References

Bruno, I. J., Cole, J. C., Kessler, M., Luo, J., Motherwell, W. D. S., Purkis, L. H., Smith, B. R., Taylor, R., Cooper, R. I., Harris, S. E. & Orpen, A. G. (2004). J. Chem. Inf. Comput. Sci. 44, 2133–2144. Web of Science CSD CrossRef PubMed CAS Google Scholar
Clarke, H. D., Arora, K. K., Bass, H., Kavuru, P., Ong, T. T., Pujari, T., Wojtas, L. & Zaworotko, M. J. (2010). Cryst. Growth Des. 10, 2152–2167. Web of Science CSD CrossRef CAS Google Scholar
Fábián, L. & Kálmán, A. (1999). Acta Cryst. B55, 1099–1108. Web of Science CrossRef IUCr Journals Google Scholar
Griesser, U. J. (2006). Polymorphism: In the Pharmaceutical Industry, edited by R. Hilfiker, pp. 211–233. Weinheim: Wiley-Vch Verlag GmbH & Co. KGaA. Google Scholar
Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. Web of Science CSD CrossRef IUCr Journals Google Scholar
Higashi, T. (1995). ABSCOR. Rigaku Corporation, Tokyo, Japan. Google Scholar
Igarashi, R., Nagase, H., Furuishi, T., Endo, T., Tomono, K. & Ueda, H. (2013). X-ray Struct. Anal. Online, 29, 23–24. CSD CrossRef Google Scholar
Igarashi, R., Nagase, H., Furuishi, T., Tomono, K., Endo, T. & Ueda, H. (2015). X-ray Struct. Anal. Online, 31, 1–2. CSD CrossRef Google Scholar
Ishida, T., In, Y., Inoue, M., Tanaka, C. & Hamanaka, N. (1990). J. Chem. Soc. Perkin Trans. 2, pp. 1085–1091. CSD CrossRef Web of Science Google Scholar
Ishida, T., In, Y., Inoue, M., Ueno, Y., Tanaka, C. & Hamanaka, N. (1989). Tetrahedron Lett. 30, 959–962. CSD CrossRef CAS Web of Science Google Scholar
Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466–470. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Miyamoto, S. (2002). Chem. Bio. Info. J, 2, 74–85. Google Scholar
Nagase, H., Kobayashi, M., Ueda, H., Furuishi, T., Gunji, M., Endo, T. & Yonemochi, E. (2016). X-ray Struct. Anal. Online, 32, 7–9. CSD CrossRef CAS Google Scholar
Putra, O. D., Yonemochi, E. & Uekusa, H. (2016d). Cryst. Growth Des. 16, 6568–6573. Google Scholar
Putra, O. D., Furuishi, T., Yonemochi, E., Terada, K. & Uekusa, H. (2016a). Cryst. Growth Des. 16, 3577–3581. CrossRef CAS Google Scholar
Putra, O. D., Umeda, D., Nugraha, Y. P., Furuishi, T., Nagase, H., Fukuzawa, K., Uekusa, H. & Yonemochi, E. (2017). CrystEngComm, 19, 2614–2622. Web of Science CSD CrossRef CAS Google Scholar
Putra, O. D., Yoshida, T., Umeda, D., Gunji, M., Uekusa, H. & Yonemochi, E. (2016c). Cryst. Growth Des. 16, 6714–6718. CrossRef CAS Google Scholar
Putra, O. D., Yoshida, T., Umeda, D., Higashi, K., Uekusa, H. & Yonemochi, E. (2016b). Cryst. Growth Des. 16, 5223–5229. Web of Science CSD CrossRef CAS Google Scholar
Ramirez, M. A. & Borja, N. L. (2008). Pharmacotherapy, 28, 646–655. Web of Science CrossRef PubMed CAS Google Scholar
Rigaku (1998). PROCESS-AUTO. Rigaku Corporation, Tokyo, Japan. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2015). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Spek, A. L. (2009). Acta Cryst. D65, 148–155. Web of Science CrossRef CAS IUCr Journals Google Scholar
Swapna, B. & Nangia, A. (2017). Cryst. Growth Des. 17, 3350–3360. CrossRef CAS Google Scholar
Swapna, B., Suresh, K. & Nangia, A. (2016). Chem. Commun. 52, 4037–4040. Web of Science CSD CrossRef CAS Google Scholar
Umeda, D., Putra, O. D., Gunji, M., Fukuzawa, K. & Yonemochi, E. (2017). Acta Cryst. E73, 941–944. CrossRef IUCr Journals Google Scholar