N-(2,6-Dimeth­oxy­pyridin-3-yl)-9-methyl-9H-carbazole-3-sulfonamide

Shan, G.; Li, Z.; Hu, L.; Jiang, J.; Liu, Z.

doi:10.1107/S1600536813007460

organic compounds

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ISSN: 2056-9890

Volume 69| Part 4| April 2013| Page o584

doi:10.1107/S1600536813007460

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N-(2,6-Dimethoxypyridin-3-yl)-9-methyl-9H-carbazole-3-sulfonamide

Guangzhi Shan,^a Zhuorong Li,^a Laixing Hu,^a Jiandong Jiang ^a and Zongying Liu ^a ^*

^aInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tiantan Xili 1#, Beijing, People's Republic of China
^*Correspondence e-mail: zongyingliu@263.net

(Received 21 February 2013; accepted 18 March 2013; online 23 March 2013)

In the title compound, C₂₀H₁₉N₃O₄S, a novel tubulin ligand active against human cancer, the dihedral angle between the pyridine ring and the carbazole ring system is 42.87 (10)°. In the crystal, the molecules are held together by N—H⋯O and C—H⋯O hydrogen bonds into layers, which are assembled into a three-dimensional network via π–π stacking interactions between inversion-related pyridine rings, with centroid–centroid distances of 3.5101 (12) Å.

Related literature

For the synthesis and properties of the compound and its derivatives, see Hu et al. (2007 ). For tubulin as a target for anticancer activity, see Wang et al. (2008 ); Jackson et al. (2007 ); Jordan et al. (1991 ); Mollinedo & Gajate (2003 ); Wilson et al. (1999 ); Yvon et al. (1999 ). For the stability of the temperature controller used for the data collection, see Cosier & Glazer (1986 ).

Experimental

Crystal data

C₂₀H₁₉N₃O₄S
M_r = 397.45
Monoclinic, P 2₁ /c
a = 13.5078 (2) Å
b = 7.9272 (1) Å
c = 20.9276 (3) Å
β = 124.027 (1)°
V = 1857.20 (4) Å³
Z = 4
Cu Kα radiation
μ = 1.83 mm⁻¹
T = 120 K
0.45 × 0.36 × 0.32 mm

Data collection

Agilent Xcalibur (Atlas, Gemini ultra) diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011 ) T_min = 0.475, T_max = 0.556
11460 measured reflections
3280 independent reflections
3161 reflections with I > 2σ(I)
R_int = 0.027

Refinement

R[F² > 2σ(F²)] = 0.034
wR(F²) = 0.088
S = 1.06
3280 reflections
262 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.45 e Å⁻³
Δρ_min = −0.52 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O3ⁱ	0.81 (2)	2.56 (2)	3.3387 (18)	163 (2)
C18—H18A⋯O1ⁱⁱ	0.96	2.45	3.398 (2)	170
C10—H10⋯O2ⁱⁱⁱ	0.93	2.56	3.4887 (19)	177
Symmetry codes: (i) x, y+1, z; (ii) $[x, -y+{\script{1\over 2}}, z+{\script{1\over 2}}]$ ; (iii) $[x, -y+{\script{3\over 2}}, z+{\script{1\over 2}}]$ .

Data collection: CrysAlis PRO (Agilent, 2011); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; 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, PLATON (Spek, 2009 ) and publCIF (Westrip, 2010 ).

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536813007460/pk2469sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536813007460/pk2469Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536813007460/pk2469Isup3.cml

checkCIF report

Comment top

Tubulin is a target for anticancer drugs (Jordan et al., 1991; Yvon et al., 1999; Wilson et al., 1999). The representative with this mode of action are the Vinca alkaloids (such as vincristine) and Taxol analogues such as paclitaxel (Jackson et al., 2007; Mollinedo et al., 2003). In this research area, N-(2,6-dimethoxypyridine-3-yl)-9-methylcarbazole-3-sulfonamide (IG-105, IMB-105) showed a promising anti-proliferative activity in human cancer cell lines. The title compound inhibits micro-tubule assembly by binding at the colchicine pocket and shows a potent anticancer activity in vitro and in vivo and was safe in mice (Wang et al., 2008).

The title molecule is shown in Fig. 1. In the crystal structure, the carbazole CH₃ hydrogens are disordered. The distance is 5.0286 (12) Å between the respective centroids of pyridine ring and the 6-membered ring C1\C2\C3\C4\C5\C6, and the dihedral angle between their planes is 42.87 (10) °. The intermolecular interactions that are present in the structure are N—H···O and C—H···O hydrogen bonds (Table 1) and π-π stacking interactions between inversion-related pyridine rings, with centroid-centroid distance = 3.5101 (12) Å (symmetry codes x, y, z and 2-x, -y, 1-z).

Related literature top

For the synthesis and properties of the compound and its derivatives, see Hu et al. (2007). For tubulin as a target for anticancer activity, see Wang et al. (2008); Jackson et al. (2007); Jordan et al. (1991); Mollinedo & Gajate (2003); Wilson et al. (1999); Yvon et al. (1999). For the stability of the temperature controller used for the data collection, see Cosier & Glazer (1986).

Experimental top

To a solution of 3-amino-2,6-dimethoxypyridine (2.6 g, 16.8 mmol) in 45 ml dimethylfornamide at room temperature, prepared 9-methylcarbazole-3-sulfonyl chloride (5.0 g, 16.9 mmol) was added. After stirring for 5 min, triethylamine (3.6 ml, 25.6 mmol) was added, with continued stirring for 2 h. After adding ice water (50 ml), the precipitate was filtered, washed with water (20 ml) and dried, recrystallized with anhydrous ethanol, dried in vacuo to give N- (2,6-dimethoxypyridine-3-yl)-9-methylcarbazole-3-sulfonamide as a colourless crystalline solid (5.2 g, 78%; mp: 170–172 °C).

¹H NMR (DMSO δ): 3.40 (3H, s), 3.69 (3H, s), 3.89 (3H, s), 6.28(1H, d, J = 8.0 Hz), 7.26 (1H, t, J = 7.2 Hz), 7.44 (1H, d, J = 8.0 Hz), 7.52(1H, dd, J = 8.0, 7.2 Hz), 7.63 (1H, d, J = 8.0 Hz), 7.70 (1H, d, J = 8.8 Hz), 7.76 (1H, d, J = 8.8 Hz), 8.21 (1H, d, J = 8.0 Hz), 8.49 (1H, s), 9.32 (1H, s).

¹³C NMR (DMSO δ): 160.2, 156.7, 142.2, 141.3, 139.3, 130.4, 126.7, 124.3, 121.6, 121.1, 120.5, 119.9, 119.8, 112.2, 109.8, 109.1, 100.6, 53.4, 52.9, 29.2.

Single crystals suitable for X-ray analysis were obtained by slow evaporation of a mixed solvent of dichloromethane and cyclohexane (3:1 v/v).

Computing details top

Data collection: CrysAlis PRO (Agilent, 2011); cell refinement: CrysAlis PRO (Agilent, 2011); data reduction: CrysAlis PRO (Agilent, 2011); 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), PLATON (Spek, 2009) and publCIF (Westrip, 2010).

Figures top

	Fig. 1. The molecular structure of title compound, showing the atom-numbering scheme. The displacement parameters are shown at the 30% probability level.
	Fig. 2. Part of packing of the title compound, viewed down the b direction. Dashed lines indicate hydrogen bonds.

N-(2,6-Dimethoxypyridin-3-yl)-9-methyl-9H-carbazole-3-sulfonamide top

Crystal data top

C₂₀H₁₉N₃O₄S	F(000) = 832
M_r = 397.45	D_x = 1.421 Mg m⁻³
Monoclinic, P2₁/c	Melting point = 443–445 K
Hall symbol: -P 2ybc	Cu Kα radiation, λ = 1.54184 Å
a = 13.5078 (2) Å	Cell parameters from 7976 reflections
b = 7.9272 (1) Å	θ = 3.3–66.7°
c = 20.9276 (3) Å	µ = 1.83 mm⁻¹
β = 124.027 (1)°	T = 120 K
V = 1857.20 (4) Å³	Block, colourless
Z = 4	0.45 × 0.36 × 0.32 mm

Data collection top

Agilent Xcalibur (Atlas, Gemini ultra) diffractometer	3280 independent reflections
Radiation source: Enhance Ultra (Cu) X-ray Source	3161 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.027
Detector resolution: 10.4713 pixels mm^-1	θ_max = 66.8°, θ_min = 4.0°
ω scans	h = −16→13
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011)	k = −9→8
T_min = 0.475, T_max = 0.556	l = −24→24
11460 measured reflections

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)] = 0.034	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.088	w = 1/[σ²(F_o²) + (0.0468P)² + 1.1436P] where P = (F_o² + 2F_c²)/3
S = 1.06	(Δ/σ)_max < 0.001
3280 reflections	Δρ_max = 0.45 e Å⁻³
262 parameters	Δρ_min = −0.52 e Å⁻³
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0078 (4)

Crystal data top

C₂₀H₁₉N₃O₄S	V = 1857.20 (4) Å³
M_r = 397.45	Z = 4
Monoclinic, P2₁/c	Cu Kα radiation
a = 13.5078 (2) Å	µ = 1.83 mm⁻¹
b = 7.9272 (1) Å	T = 120 K
c = 20.9276 (3) Å	0.45 × 0.36 × 0.32 mm
β = 124.027 (1)°

Data collection top

Agilent Xcalibur (Atlas, Gemini ultra) diffractometer	3280 independent reflections
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011)	3161 reflections with I > 2σ(I)
T_min = 0.475, T_max = 0.556	R_int = 0.027
11460 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.034	0 restraints
wR(F²) = 0.088	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	Δρ_max = 0.45 e Å⁻³
3280 reflections	Δρ_min = −0.52 e Å⁻³
262 parameters

Special details top

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems open-flow nitrogen cryostat (Cosier & Glazer, 1986) with a nominal stability of 0.1 K.

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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	Occ. (<1)
S1	0.69096 (3)	0.28850 (4)	0.403260 (19)	0.01331 (14)
O1	0.62355 (9)	0.15207 (14)	0.35261 (6)	0.0178 (3)
O2	0.68743 (10)	0.45199 (14)	0.37286 (6)	0.0195 (3)
O3	0.95214 (10)	−0.42247 (14)	0.55767 (6)	0.0209 (3)
O4	0.93551 (10)	0.14336 (14)	0.60496 (6)	0.0208 (3)
N1	0.83268 (12)	0.22943 (17)	0.45142 (8)	0.0152 (3)
H1	0.8755 (17)	0.301 (3)	0.4817 (11)	0.019 (5)*
N2	0.94314 (11)	−0.14034 (16)	0.58206 (7)	0.0166 (3)
N3	0.59643 (11)	0.36785 (16)	0.64261 (7)	0.0167 (3)
C1	0.65608 (13)	0.30951 (19)	0.47199 (8)	0.0137 (3)
C2	0.61415 (13)	0.16778 (19)	0.48958 (9)	0.0161 (3)
H2	0.6013	0.0675	0.4629	0.019*
C3	0.59167 (13)	0.1756 (2)	0.54624 (9)	0.0169 (3)
H3	0.5632	0.0822	0.5581	0.020*
C4	0.61299 (13)	0.32797 (19)	0.58516 (8)	0.0148 (3)
C5	0.65942 (13)	0.46985 (18)	0.56913 (8)	0.0141 (3)
C6	0.67969 (13)	0.46111 (19)	0.51119 (8)	0.0143 (3)
H6	0.7082	0.5539	0.4990	0.017*
C7	0.67359 (13)	0.6016 (2)	0.62161 (8)	0.0158 (3)
C8	0.63249 (13)	0.5339 (2)	0.66488 (8)	0.0163 (3)
C9	0.63143 (14)	0.6286 (2)	0.72079 (9)	0.0203 (3)
H9	0.6032	0.5837	0.7488	0.024*
C10	0.67411 (15)	0.7918 (2)	0.73269 (9)	0.0224 (4)
H10	0.6743	0.8583	0.7694	0.027*
C11	0.71695 (15)	0.8595 (2)	0.69094 (9)	0.0219 (4)
H11	0.7462	0.9693	0.7009	0.026*
C12	0.71658 (14)	0.7660 (2)	0.63491 (9)	0.0188 (3)
H12	0.7444	0.8121	0.6069	0.023*
C13	0.91249 (13)	0.01614 (19)	0.55524 (9)	0.0150 (3)
C14	0.86006 (13)	0.05938 (19)	0.47790 (8)	0.0141 (3)
C15	0.83742 (13)	−0.0704 (2)	0.42735 (9)	0.0160 (3)
H15	0.8028	−0.0469	0.3754	0.019*
C16	0.86582 (13)	−0.2349 (2)	0.45332 (9)	0.0173 (3)
H16	0.8493	−0.3239	0.4198	0.021*
C17	0.92017 (13)	−0.26123 (19)	0.53180 (9)	0.0163 (3)
C18	0.54002 (16)	0.2605 (2)	0.66988 (10)	0.0239 (4)
H18A	0.5740	0.2834	0.7234	0.036*	0.61 (2)
H18B	0.5530	0.1443	0.6637	0.036*	0.61 (2)
H18C	0.4558	0.2831	0.6405	0.036*	0.61 (2)
H18D	0.4812	0.1905	0.6284	0.036*	0.39 (2)
H18E	0.5022	0.3296	0.6880	0.036*	0.39 (2)
H18F	0.5994	0.1908	0.7112	0.036*	0.39 (2)
C19	0.99079 (19)	0.0978 (2)	0.68440 (10)	0.0319 (4)
H19A	0.9996	0.1965	0.7137	0.048*
H19B	1.0680	0.0497	0.7041	0.048*
H19C	0.9418	0.0167	0.6885	0.048*
C20	1.01784 (18)	−0.4455 (2)	0.63937 (10)	0.0326 (4)
H20A	1.0864	−0.3728	0.6641	0.049*
H20B	1.0434	−0.5608	0.6518	0.049*
H20C	0.9678	−0.4185	0.6571	0.049*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0165 (2)	0.0117 (2)	0.0116 (2)	0.00097 (13)	0.00782 (16)	0.00084 (13)
O1	0.0184 (5)	0.0184 (6)	0.0143 (5)	0.0000 (4)	0.0077 (4)	−0.0026 (4)
O2	0.0266 (6)	0.0147 (6)	0.0192 (6)	0.0027 (4)	0.0141 (5)	0.0049 (4)
O3	0.0268 (6)	0.0119 (5)	0.0196 (6)	0.0000 (4)	0.0103 (5)	0.0013 (4)
O4	0.0320 (6)	0.0150 (6)	0.0142 (5)	−0.0026 (5)	0.0123 (5)	−0.0031 (4)
N1	0.0163 (7)	0.0117 (7)	0.0168 (7)	−0.0023 (5)	0.0088 (6)	−0.0022 (5)
N2	0.0185 (6)	0.0149 (7)	0.0160 (6)	−0.0023 (5)	0.0094 (5)	−0.0001 (5)
N3	0.0223 (7)	0.0151 (7)	0.0159 (6)	−0.0003 (5)	0.0128 (6)	0.0003 (5)
C1	0.0148 (7)	0.0133 (7)	0.0118 (7)	0.0011 (6)	0.0067 (6)	0.0000 (6)
C2	0.0188 (7)	0.0107 (7)	0.0180 (7)	−0.0013 (6)	0.0098 (6)	−0.0025 (6)
C3	0.0207 (8)	0.0121 (7)	0.0193 (8)	−0.0025 (6)	0.0121 (7)	0.0009 (6)
C4	0.0160 (7)	0.0144 (7)	0.0134 (7)	0.0018 (6)	0.0078 (6)	0.0018 (6)
C5	0.0152 (7)	0.0108 (7)	0.0134 (7)	0.0010 (6)	0.0062 (6)	−0.0003 (6)
C6	0.0152 (7)	0.0115 (7)	0.0155 (7)	−0.0001 (6)	0.0081 (6)	0.0014 (6)
C7	0.0161 (7)	0.0145 (7)	0.0134 (7)	0.0028 (6)	0.0062 (6)	−0.0006 (6)
C8	0.0172 (7)	0.0156 (8)	0.0123 (7)	0.0039 (6)	0.0060 (6)	0.0012 (6)
C9	0.0221 (8)	0.0232 (9)	0.0137 (7)	0.0056 (6)	0.0089 (7)	0.0001 (6)
C10	0.0248 (8)	0.0222 (9)	0.0141 (7)	0.0068 (7)	0.0071 (7)	−0.0038 (6)
C11	0.0232 (8)	0.0153 (8)	0.0187 (8)	0.0014 (6)	0.0064 (7)	−0.0045 (6)
C12	0.0209 (8)	0.0150 (8)	0.0172 (8)	0.0014 (6)	0.0086 (7)	0.0000 (6)
C13	0.0160 (7)	0.0138 (7)	0.0158 (7)	−0.0031 (6)	0.0093 (6)	−0.0033 (6)
C14	0.0137 (7)	0.0126 (7)	0.0158 (7)	−0.0004 (6)	0.0081 (6)	−0.0001 (6)
C15	0.0148 (7)	0.0181 (8)	0.0141 (7)	−0.0004 (6)	0.0075 (6)	−0.0011 (6)
C16	0.0186 (8)	0.0147 (8)	0.0179 (8)	−0.0025 (6)	0.0097 (6)	−0.0042 (6)
C17	0.0163 (7)	0.0121 (7)	0.0202 (8)	−0.0024 (6)	0.0101 (6)	−0.0002 (6)
C18	0.0367 (10)	0.0200 (8)	0.0252 (9)	0.0000 (7)	0.0235 (8)	0.0021 (7)
C19	0.0539 (12)	0.0235 (9)	0.0157 (8)	−0.0099 (8)	0.0179 (8)	−0.0045 (7)
C20	0.0452 (11)	0.0200 (9)	0.0190 (8)	0.0022 (8)	0.0096 (8)	0.0048 (7)

Geometric parameters (Å, º) top

S1—O1	1.4291 (11)	C8—C9	1.397 (2)
S1—O2	1.4327 (11)	C9—C10	1.381 (2)
S1—N1	1.6554 (13)	C9—H9	0.9300
S1—C1	1.7542 (15)	C10—C11	1.397 (3)
O3—C17	1.3608 (19)	C10—H10	0.9300
O3—C20	1.430 (2)	C11—C12	1.385 (2)
O4—C13	1.3543 (18)	C11—H11	0.9300
O4—C19	1.436 (2)	C12—H12	0.9300
N1—C14	1.425 (2)	C13—C14	1.399 (2)
N1—H1	0.80 (2)	C14—C15	1.382 (2)
N2—C17	1.325 (2)	C15—C16	1.382 (2)
N2—C13	1.329 (2)	C15—H15	0.9300
N3—C4	1.3770 (19)	C16—C17	1.390 (2)
N3—C8	1.390 (2)	C16—H16	0.9300
N3—C18	1.455 (2)	C18—H18A	0.9600
C1—C6	1.388 (2)	C18—H18B	0.9600
C1—C2	1.397 (2)	C18—H18C	0.9600
C2—C3	1.380 (2)	C18—H18D	0.9600
C2—H2	0.9300	C18—H18E	0.9600
C3—C4	1.394 (2)	C18—H18F	0.9600
C3—H3	0.9300	C19—H19A	0.9600
C4—C5	1.416 (2)	C19—H19B	0.9600
C5—C6	1.386 (2)	C19—H19C	0.9600
C5—C7	1.449 (2)	C20—H20A	0.9600
C6—H6	0.9300	C20—H20B	0.9600
C7—C12	1.390 (2)	C20—H20C	0.9600
C7—C8	1.407 (2)

O1—S1—O2	120.41 (6)	C7—C12—H12	120.8
O1—S1—N1	106.10 (7)	N2—C13—O4	119.17 (13)
O2—S1—N1	105.43 (7)	N2—C13—C14	123.64 (14)
O1—S1—C1	109.15 (7)	O4—C13—C14	117.16 (13)
O2—S1—C1	108.71 (7)	C15—C14—C13	117.10 (14)
N1—S1—C1	106.10 (7)	C15—C14—N1	120.55 (13)
C17—O3—C20	116.23 (13)	C13—C14—N1	122.34 (13)
C13—O4—C19	116.68 (12)	C14—C15—C16	120.50 (14)
C14—N1—S1	117.67 (10)	C14—C15—H15	119.7
C14—N1—H1	116.4 (14)	C16—C15—H15	119.7
S1—N1—H1	110.9 (13)	C15—C16—C17	116.98 (14)
C17—N2—C13	117.44 (13)	C15—C16—H16	121.5
C4—N3—C8	108.21 (13)	C17—C16—H16	121.5
C4—N3—C18	125.79 (13)	N2—C17—O3	118.84 (14)
C8—N3—C18	125.74 (13)	N2—C17—C16	124.31 (14)
C6—C1—C2	122.25 (14)	O3—C17—C16	116.85 (14)
C6—C1—S1	119.24 (11)	N3—C18—H18A	109.5
C2—C1—S1	118.31 (11)	N3—C18—H18B	109.5
C3—C2—C1	120.44 (14)	H18A—C18—H18B	109.5
C3—C2—H2	119.8	N3—C18—H18C	109.5
C1—C2—H2	119.8	H18A—C18—H18C	109.5
C2—C3—C4	117.92 (14)	H18B—C18—H18C	109.5
C2—C3—H3	121.0	N3—C18—H18D	109.5
C4—C3—H3	121.0	H18A—C18—H18D	141.1
N3—C4—C3	128.88 (14)	H18B—C18—H18D	56.3
N3—C4—C5	109.52 (13)	H18C—C18—H18D	56.3
C3—C4—C5	121.59 (14)	N3—C18—H18E	109.5
C6—C5—C4	119.85 (13)	H18A—C18—H18E	56.3
C6—C5—C7	133.80 (14)	H18B—C18—H18E	141.1
C4—C5—C7	106.34 (13)	H18C—C18—H18E	56.3
C5—C6—C1	117.89 (14)	H18D—C18—H18E	109.5
C5—C6—H6	121.1	N3—C18—H18F	109.5
C1—C6—H6	121.1	H18A—C18—H18F	56.3
C12—C7—C8	120.01 (14)	H18B—C18—H18F	56.3
C12—C7—C5	133.71 (15)	H18C—C18—H18F	141.1
C8—C7—C5	106.28 (13)	H18D—C18—H18F	109.5
N3—C8—C9	128.59 (15)	H18E—C18—H18F	109.5
N3—C8—C7	109.63 (13)	O4—C19—H19A	109.5
C9—C8—C7	121.78 (15)	O4—C19—H19B	109.5
C10—C9—C8	117.10 (15)	H19A—C19—H19B	109.5
C10—C9—H9	121.5	O4—C19—H19C	109.5
C8—C9—H9	121.5	H19A—C19—H19C	109.5
C9—C10—C11	121.62 (15)	H19B—C19—H19C	109.5
C9—C10—H10	119.2	O3—C20—H20A	109.5
C11—C10—H10	119.2	O3—C20—H20B	109.5
C12—C11—C10	121.16 (16)	H20A—C20—H20B	109.5
C12—C11—H11	119.4	O3—C20—H20C	109.5
C10—C11—H11	119.4	H20A—C20—H20C	109.5
C11—C12—C7	118.33 (15)	H20B—C20—H20C	109.5
C11—C12—H12	120.8

O1—S1—N1—C14	−41.52 (12)	C4—N3—C8—C7	−0.40 (16)
O2—S1—N1—C14	−170.29 (11)	C18—N3—C8—C7	−174.84 (14)
C1—S1—N1—C14	74.49 (12)	C12—C7—C8—N3	−178.80 (13)
O1—S1—C1—C6	−159.85 (11)	C5—C7—C8—N3	1.12 (16)
O2—S1—C1—C6	−26.75 (14)	C12—C7—C8—C9	1.1 (2)
N1—S1—C1—C6	86.21 (13)	C5—C7—C8—C9	−178.95 (13)
O1—S1—C1—C2	25.18 (14)	N3—C8—C9—C10	179.09 (15)
O2—S1—C1—C2	158.28 (11)	C7—C8—C9—C10	−0.8 (2)
N1—S1—C1—C2	−88.76 (13)	C8—C9—C10—C11	−0.2 (2)
C6—C1—C2—C3	1.7 (2)	C9—C10—C11—C12	1.0 (2)
S1—C1—C2—C3	176.48 (11)	C10—C11—C12—C7	−0.7 (2)
C1—C2—C3—C4	−0.5 (2)	C8—C7—C12—C11	−0.3 (2)
C8—N3—C4—C3	178.69 (15)	C5—C7—C12—C11	179.77 (16)
C18—N3—C4—C3	−6.9 (3)	C17—N2—C13—O4	−179.41 (13)
C8—N3—C4—C5	−0.51 (16)	C17—N2—C13—C14	−1.3 (2)
C18—N3—C4—C5	173.93 (14)	C19—O4—C13—N2	−1.0 (2)
C2—C3—C4—N3	179.15 (14)	C19—O4—C13—C14	−179.21 (15)
C2—C3—C4—C5	−1.7 (2)	N2—C13—C14—C15	1.4 (2)
N3—C4—C5—C6	−177.87 (13)	O4—C13—C14—C15	179.54 (13)
C3—C4—C5—C6	2.9 (2)	N2—C13—C14—N1	−177.34 (13)
N3—C4—C5—C7	1.19 (16)	O4—C13—C14—N1	0.8 (2)
C3—C4—C5—C7	−178.08 (13)	S1—N1—C14—C15	76.61 (16)
C4—C5—C6—C1	−1.7 (2)	S1—N1—C14—C13	−104.69 (15)
C7—C5—C6—C1	179.60 (15)	C13—C14—C15—C16	0.2 (2)
C2—C1—C6—C5	−0.5 (2)	N1—C14—C15—C16	178.92 (13)
S1—C1—C6—C5	−175.32 (11)	C14—C15—C16—C17	−1.6 (2)
C6—C5—C7—C12	−2.6 (3)	C13—N2—C17—O3	179.01 (13)
C4—C5—C7—C12	178.51 (16)	C13—N2—C17—C16	−0.4 (2)
C6—C5—C7—C8	177.48 (16)	C20—O3—C17—N2	−5.0 (2)
C4—C5—C7—C8	−1.39 (16)	C20—O3—C17—C16	174.38 (15)
C4—N3—C8—C9	179.67 (15)	C15—C16—C17—N2	1.8 (2)
C18—N3—C8—C9	5.2 (2)	C15—C16—C17—O3	−177.58 (13)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O3ⁱ	0.81 (2)	2.56 (2)	3.3387 (18)	163 (2)
C18—H18A···O1ⁱⁱ	0.96	2.45	3.398 (2)	170
C10—H10···O2ⁱⁱⁱ	0.93	2.56	3.4887 (19)	177

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

Experimental details

Crystal data
Chemical formula	C₂₀H₁₉N₃O₄S
M_r	397.45
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	120
a, b, c (Å)	13.5078 (2), 7.9272 (1), 20.9276 (3)
β (°)	124.027 (1)
V (Å³)	1857.20 (4)
Z	4
Radiation type	Cu Kα
µ (mm⁻¹)	1.83
Crystal size (mm)	0.45 × 0.36 × 0.32

Data collection
Diffractometer	Agilent Xcalibur (Atlas, Gemini ultra) diffractometer
Absorption correction	Multi-scan (CrysAlis PRO; Agilent, 2011)
T_min, T_max	0.475, 0.556
No. of measured, independent and observed [I > 2σ(I)] reflections	11460, 3280, 3161
R_int	0.027
(sin θ/λ)_max (Å⁻¹)	0.596

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.034, 0.088, 1.06
No. of reflections	3280
No. of parameters	262
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.45, −0.52

Computer programs: CrysAlis PRO (Agilent, 2011), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008), PLATON (Spek, 2009) and publCIF (Westrip, 2010).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O3ⁱ	0.81 (2)	2.56 (2)	3.3387 (18)	163 (2)
C18—H18A···O1ⁱⁱ	0.96	2.45	3.398 (2)	169.7
C10—H10···O2ⁱⁱⁱ	0.93	2.56	3.4887 (19)	176.5

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

Acknowledgements

This work was supported by the National Natural Science Foundation of China (30901840) and the New Teachers' Fund for Doctor Stations, Ministry of Education (20101106120032).

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