Bosentan monohydrate

Kaur, M.; Jasinski, J.P.; Keeley, A.C.; Yathirajan, H.S.; Betz, R.; Gerber, T.; Butcher, R.J.

doi:10.1107/S1600536812048969

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 69| Part 1| January 2013| Pages o12-o13

https://doi.org/10.1107/S1600536812048969

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Bosentan monohydrate

Manpreet Kaur,^a Jerry P. Jasinski,^b ^* Amanda C. Keeley,^b H. S. Yathirajan,^a Richard Betz,^c Thomas Gerber ^c and Ray J. Butcher ^d

^aDepartment of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, India, ^bDepartment of Chemistry, Keene State College, 229 Main Street, Keene, NH 03435-2001, USA, ^cNelson Mandela Metropolitan University, Summerstrand Campus, Department of Chemistry, University Way, Summerstrand, PP Box 77000, Port Elizabeth 6031, South Africa, and ^dDepartment of Chemistry, Howard University, 525 College Street NW, Washington, DC 20059, USA
^*Correspondence e-mail: jjasinski@keene.edu

(Received 28 November 2012; accepted 29 November 2012; online 5 December 2012)

In the title compound, C₂₇H₂₉N₅O₆S·H₂O {systematic name: 4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]benzene-1-sulfonamide monohydrate], the dihedral angle between the mean planes of the pyrimidine rings is 27.0 (1)°. The dihedral angle between the mean planes of the benzene rings is 47.7 (8)°, forming a U-shaped channel around the chain of twisted pyrimidine rings. The crystal packing is stabilized by O—H⋯O, O—H⋯N and N—H⋯O hydrogen bonds with a single water molecule, and weak O—H⋯N intermolecular interactions between the hydroxy group and one of the pyrimidine rings producing an two-dimensional supramolecular array in the bc plane. The title compound studied was a merohedral twin with the major component being approximately 57%.

Related literature

For reviews of bosentan in the management of pulmonary arterial hypertension and systemic sclerosis, see: Gabbay et al. (2007 ); Kumar et al. (2011 ); Oldfield & Lyseng-Williamson (2006 ). For related structures, see: Singh et al. (1985 ); El-Ghamry et al. (2008 ); Kant et al. (2012 ).

Experimental

Crystal data

C₂₇H₂₉N₅O₆S·H₂O
M_r = 569.63
Monoclinic, P 2₁ /c
a = 12.3393 (4) Å
b = 15.1238 (6) Å
c = 14.6988 (4) Å
β = 95.037 (3)°
V = 2732.46 (16) Å³
Z = 4
Cu Kα radiation
μ = 1.52 mm⁻¹
T = 123 K
0.79 × 0.43 × 0.22 mm

Data collection

Agilent Xcalibur (Ruby, Gemini) diffractometer
Absorption correction: analytical (CrysAlis RED; Agilent, 2012 ) T_min = 0.535, T_max = 0.766
9563 measured reflections
9563 independent reflections
7477 reflections with I > 2σ(I)

Refinement

R[F² > 2σ(F²)] = 0.055
wR(F²) = 0.163
S = 1.03
9563 reflections
373 parameters
3 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.44 e Å⁻³
Δρ_min = −0.77 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O6—H6⋯N3ⁱ	0.84	2.51	3.317 (2)	162
O6—H6⋯N4ⁱ	0.84	2.60	3.141 (2)	124
O1W—H1W⋯O4	0.80 (2)	2.30 (2)	3.013 (2)	150 (3)
O1W—H2W⋯N4ⁱⁱ	0.81 (2)	2.07 (2)	2.873 (2)	174 (3)
N1—H1A⋯O1W	0.88	1.87	2.721 (2)	163
Symmetry codes: (i) -x+2, -y+1, -z+1; (ii) $[x, -y+{\script{1\over 2}}, z+{\script{1\over 2}}]$ .

Data collection: CrysAlis PRO (Agilent, 2012); cell refinement: CrysAlis PRO; data reduction: CrysAlis RED (Agilent, 2012); 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 global, I. DOI: https://doi.org/10.1107/S1600536812048969/tk5176sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536812048969/tk5176Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S1600536812048969/tk5176Isup3.cml

checkCIF report

Comment top

Bosentan (chemically, 4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy) -2-(pyrimidin-2-yl)pyrimidin-4-yl]benzene-1-sulfonamide) is a dual endothelin receptor antagonist used in the treatment of pulmonary artery hypertension (PAH). Bosentan is used to treat pulmonary hypertension by blocking the action of endothelin molecules that would otherwise promote narrowing of the blood vessels and lead to high blood pressure. A review of bosentan in the management of pulmonary arterial hypertension is published (Gabbay et al., 2007). Another review on the use of bosentan in pulmonary arterial hypertension and systemic sclerosis is also published (Oldfield & Lyseng-Williamson, 2006). A spectrophotometric method for the determination of bosentan monohydrate in bulk and pharmaceutical dosage forms is reported (Kumar et al., 2011). The crystal structures of some related compounds, viz., N1-(2,6-dimethyl-4-pyrimidinyl)sulphanilamide (Singh et al., 1985), 4-[(3-formyl-4-hydroxyphenyl)diazenyl]-N-(pyrimidin-2-yl)benzenesulfonamide (El-Ghamry et al., 2008) and N-(2-{[5-bromo-2-(morpholin-4-yl)pyrimidin-4-yl]sulfanyl}-4-methoxyphenyl)- 4-methyl benzenesulfonamide (Kant et al., 2012), have been reported. In view of the importance of the title compound, (I), the paper reports its crystal structure.

In (I), the dihedral angle between the mean planes of the two pyrimidine rings is 27.0 (1)° (Fig. 1). The dihedral angle between the mean planes of the two benzene rings is 47.7 (8)° forming a U-shaped channel around the chain of twisted pyrimidine rings. Crystal packing is stabilized by O—H···O, O—H···N and N—H···O hydrogen bonds with a single water molecule and weak O—H···N intermolecular interactions between the hydroxy group and one of the nearby pyrimidine rings (Fig. 2).

Related literature top

For reviews of bosentan in the management of pulmonary arterial hypertension and systemic sclerosis, see: Gabbay et al. (2007); Kumar et al. (2011); Oldfield & Lyseng-Williamson (2006). For related structures, see: Singh et al. (1985); El-Ghamry et al. (2008); Kant et al. (2012).

Experimental top

The title compound was obtained as a gift sample from R. L. Fine Chem, Bengaluru, India. X-ray quality crystals were obtained by slow evaporation of ethanol solution (m.p.: 383–385 K).

Structure description top

For reviews of bosentan in the management of pulmonary arterial hypertension and systemic sclerosis, see: Gabbay et al. (2007); Kumar et al. (2011); Oldfield & Lyseng-Williamson (2006). For related structures, see: Singh et al. (1985); El-Ghamry et al. (2008); Kant et al. (2012).

Computing details top

Data collection: CrysAlis PRO (Agilent, 2012); cell refinement: CrysAlis PRO (Agilent, 2012); data reduction: CrysAlis RED (Agilent, 2012); 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. Molecular structure of the title compound showing the atom labeling scheme and 30% probability displacement ellipsoids. The dashed indicates N1—H1···O1W hydrogen bonding within the asymmetric unit.
	Fig. 2. Packing diagram of the title compound viewed along the a axis. Dashed lines indicate O—H···O, O—H···N and N—H···O hydrogen bonds with a single water molecule and weak O—H···N intermolecular interactions between the hydroxy group and one of the nearby pyrimidine rings. The remaining H atoms have been removed for clarity.

4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)- 2-(pyrimidin-2-yl)pyrimidin-4-yl]benzene-1-sulfonamide monohydrate top

Crystal data top

C₂₇H₂₉N₅O₆S·H₂O	F(000) = 1200
M_r = 569.63	D_x = 1.385 Mg m⁻³
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.54184 Å
Hall symbol: -P 2ybc	Cell parameters from 3219 reflections
a = 12.3393 (4) Å	θ = 2.9–75.5°
b = 15.1238 (6) Å	µ = 1.52 mm⁻¹
c = 14.6988 (4) Å	T = 123 K
β = 95.037 (3)°	Prism, colourless
V = 2732.46 (16) Å³	0.79 × 0.43 × 0.22 mm
Z = 4

Data collection top

Agilent Xcalibur (Ruby, Gemini) diffractometer	9563 independent reflections
Radiation source: Enhance (Cu) X-ray Source	7477 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.000
Detector resolution: 10.5081 pixels mm^-1	θ_max = 76.1°, θ_min = 3.6°
ω scans	h = −15→14
Absorption correction: analytical (CrysAlis PRO; Agilent, 2012)	k = −18→18
T_min = 0.535, T_max = 0.766	l = −18→18
9563 measured reflections

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)] = 0.055	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.163	H atoms treated by a mixture of independent and constrained refinement
S = 1.03	w = 1/[σ²(F_o²) + (0.1185P)²] where P = (F_o² + 2F_c²)/3
9563 reflections	(Δ/σ)_max < 0.001
373 parameters	Δρ_max = 0.44 e Å⁻³
3 restraints	Δρ_min = −0.77 e Å⁻³

Crystal data top

C₂₇H₂₉N₅O₆S·H₂O	V = 2732.46 (16) Å³
M_r = 569.63	Z = 4
Monoclinic, P2₁/c	Cu Kα radiation
a = 12.3393 (4) Å	µ = 1.52 mm⁻¹
b = 15.1238 (6) Å	T = 123 K
c = 14.6988 (4) Å	0.79 × 0.43 × 0.22 mm
β = 95.037 (3)°

Data collection top

Agilent Xcalibur (Ruby, Gemini) diffractometer	9563 independent reflections
Absorption correction: analytical (CrysAlis PRO; Agilent, 2012)	7477 reflections with I > 2σ(I)
T_min = 0.535, T_max = 0.766	R_int = 0.000
9563 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.055	3 restraints
wR(F²) = 0.163	H atoms treated by a mixture of independent and constrained refinement
S = 1.03	Δρ_max = 0.44 e Å⁻³
9563 reflections	Δρ_min = −0.77 e Å⁻³
373 parameters

Special details top

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
S1	0.61088 (3)	0.25246 (3)	0.77145 (3)	0.02158 (12)
O1	0.52137 (11)	0.26956 (9)	0.70499 (10)	0.0278 (3)
O2	0.60422 (11)	0.17933 (9)	0.83307 (9)	0.0286 (3)
O3	0.90811 (10)	0.17574 (9)	0.64520 (9)	0.0223 (3)
O4	1.00833 (11)	0.03046 (9)	0.69883 (10)	0.0319 (3)
O5	0.96944 (10)	0.26749 (8)	0.49814 (9)	0.0211 (3)
O6	1.06737 (13)	0.43628 (11)	0.54935 (14)	0.0466 (5)
H6	1.0995	0.4851	0.5474	0.056*
O1W	0.80006 (14)	0.07096 (12)	0.78315 (12)	0.0431 (4)
H1W	0.8518 (18)	0.0432 (19)	0.772 (2)	0.065*
H2W	0.774 (2)	0.050 (2)	0.8265 (16)	0.065*
N1	0.72198 (13)	0.23031 (11)	0.72150 (11)	0.0240 (3)
H1A	0.7601	0.1839	0.7413	0.029*
N2	0.70609 (12)	0.35062 (10)	0.62171 (10)	0.0201 (3)
N3	0.83084 (11)	0.37054 (10)	0.50764 (10)	0.0193 (3)
N4	0.69029 (12)	0.49778 (11)	0.43244 (10)	0.0228 (3)
N5	0.63133 (12)	0.51751 (10)	0.58109 (11)	0.0216 (3)
C1	0.63930 (15)	0.34843 (13)	0.83661 (13)	0.0234 (4)
C2	0.61384 (14)	0.43168 (13)	0.80149 (12)	0.0229 (4)
H2A	0.5839	0.4383	0.7401	0.027*
C3	0.63269 (15)	0.50540 (13)	0.85735 (13)	0.0254 (4)
H3A	0.6144	0.5624	0.8337	0.031*
C4	0.67792 (16)	0.49731 (14)	0.94734 (13)	0.0274 (4)
C5	0.7032 (2)	0.41272 (16)	0.97988 (15)	0.0376 (5)
H5A	0.7348	0.4058	1.0407	0.045*
C6	0.68348 (19)	0.33858 (15)	0.92605 (15)	0.0354 (5)
H6A	0.7001	0.2814	0.9501	0.042*
C7	0.70065 (18)	0.57723 (14)	1.01064 (14)	0.0315 (4)
C8	0.6619 (3)	0.66378 (17)	0.96631 (19)	0.0588 (8)
H8A	0.5833	0.6609	0.9501	0.088*
H8B	0.6993	0.6736	0.9110	0.088*
H8C	0.6783	0.7126	1.0092	0.088*
C9	0.8239 (2)	0.5843 (2)	1.03558 (19)	0.0508 (7)
H9A	0.8390	0.6337	1.0779	0.076*
H9B	0.8607	0.5944	0.9801	0.076*
H9C	0.8507	0.5292	1.0647	0.076*
C10	0.6441 (2)	0.56343 (18)	1.09732 (16)	0.0451 (6)
H10A	0.5657	0.5565	1.0816	0.068*
H10B	0.6571	0.6148	1.1375	0.068*
H10C	0.6729	0.5102	1.1288	0.068*
C11	0.76040 (14)	0.27812 (12)	0.65145 (12)	0.0193 (4)
C12	0.85494 (14)	0.25075 (12)	0.61345 (12)	0.0194 (3)
C13	0.88431 (14)	0.29866 (12)	0.53861 (12)	0.0193 (3)
C14	0.74497 (13)	0.39270 (12)	0.55183 (12)	0.0189 (4)
C15	0.68504 (13)	0.47494 (12)	0.51997 (12)	0.0192 (3)
C16	0.63172 (15)	0.56851 (13)	0.40389 (13)	0.0251 (4)
H16A	0.6321	0.5865	0.3420	0.030*
C17	0.57088 (15)	0.61632 (12)	0.46094 (14)	0.0249 (4)
H17A	0.5281	0.6655	0.4395	0.030*
C18	0.57539 (14)	0.58898 (12)	0.55099 (14)	0.0244 (4)
H18A	0.5374	0.6222	0.5929	0.029*
C19	1.01482 (14)	0.18540 (13)	0.68486 (12)	0.0221 (4)
C20	1.06708 (15)	0.10674 (13)	0.71295 (13)	0.0252 (4)
C21	1.17366 (16)	0.11063 (15)	0.75333 (13)	0.0301 (4)
H21A	1.2102	0.0578	0.7729	0.036*
C22	1.22647 (16)	0.19136 (16)	0.76497 (13)	0.0328 (5)
H22A	1.2990	0.1936	0.7925	0.039*
C23	1.17412 (16)	0.26824 (15)	0.73685 (14)	0.0300 (4)
H23A	1.2105	0.3234	0.7451	0.036*
C24	1.06718 (15)	0.26529 (13)	0.69604 (12)	0.0245 (4)
H24A	1.0311	0.3183	0.6762	0.029*
C25	1.06856 (19)	−0.05017 (16)	0.7061 (2)	0.0476 (7)
H25A	1.0213	−0.0994	0.6847	0.071*
H25B	1.0954	−0.0601	0.7701	0.071*
H25C	1.1303	−0.0464	0.6687	0.071*
C26	1.02013 (15)	0.32487 (12)	0.43522 (12)	0.0233 (4)
H26A	0.9652	0.3658	0.4056	0.028*
H26B	1.0502	0.2890	0.3870	0.028*
C27	1.10957 (16)	0.37666 (15)	0.48616 (15)	0.0323 (5)
H27A	1.1613	0.3355	0.5195	0.039*
H27B	1.1498	0.4104	0.4422	0.039*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0224 (2)	0.0212 (2)	0.0225 (2)	−0.00108 (16)	0.00979 (17)	0.00304 (17)
O1	0.0249 (6)	0.0310 (7)	0.0278 (7)	−0.0014 (6)	0.0043 (5)	0.0023 (6)
O2	0.0328 (7)	0.0243 (7)	0.0309 (7)	−0.0008 (5)	0.0143 (6)	0.0062 (6)
O3	0.0210 (6)	0.0199 (6)	0.0267 (6)	0.0018 (5)	0.0055 (5)	0.0054 (5)
O4	0.0299 (7)	0.0247 (7)	0.0424 (8)	0.0056 (6)	0.0109 (6)	0.0106 (6)
O5	0.0216 (6)	0.0202 (6)	0.0228 (6)	0.0026 (5)	0.0095 (5)	0.0023 (5)
O6	0.0369 (8)	0.0366 (9)	0.0694 (12)	−0.0127 (7)	0.0228 (8)	−0.0265 (9)
O1W	0.0474 (9)	0.0412 (10)	0.0453 (10)	0.0189 (7)	0.0300 (8)	0.0228 (8)
N1	0.0266 (8)	0.0201 (8)	0.0271 (8)	0.0047 (6)	0.0125 (6)	0.0057 (6)
N2	0.0211 (7)	0.0189 (7)	0.0209 (7)	0.0013 (6)	0.0060 (6)	0.0008 (6)
N3	0.0213 (7)	0.0196 (7)	0.0174 (7)	0.0011 (6)	0.0050 (6)	0.0005 (6)
N4	0.0250 (7)	0.0230 (8)	0.0211 (7)	0.0019 (6)	0.0056 (6)	0.0018 (6)
N5	0.0216 (7)	0.0201 (7)	0.0238 (7)	0.0004 (6)	0.0055 (6)	−0.0004 (6)
C1	0.0250 (8)	0.0220 (9)	0.0244 (9)	0.0010 (7)	0.0082 (7)	0.0005 (7)
C2	0.0248 (8)	0.0247 (9)	0.0200 (8)	0.0008 (7)	0.0070 (7)	0.0040 (7)
C3	0.0276 (9)	0.0258 (9)	0.0238 (9)	0.0020 (7)	0.0075 (7)	0.0051 (8)
C4	0.0318 (10)	0.0272 (10)	0.0238 (9)	0.0008 (8)	0.0053 (8)	−0.0014 (8)
C5	0.0529 (13)	0.0321 (11)	0.0262 (10)	0.0074 (10)	−0.0055 (9)	0.0013 (9)
C6	0.0473 (12)	0.0284 (11)	0.0295 (11)	0.0073 (9)	−0.0014 (9)	0.0056 (9)
C7	0.0409 (11)	0.0285 (11)	0.0255 (10)	0.0000 (9)	0.0046 (8)	−0.0042 (9)
C8	0.105 (2)	0.0305 (13)	0.0398 (14)	0.0115 (14)	−0.0028 (15)	−0.0075 (11)
C9	0.0438 (13)	0.0553 (16)	0.0545 (16)	−0.0129 (12)	0.0121 (12)	−0.0205 (14)
C10	0.0534 (14)	0.0508 (15)	0.0335 (12)	−0.0131 (12)	0.0168 (11)	−0.0133 (11)
C11	0.0226 (8)	0.0179 (8)	0.0183 (8)	−0.0028 (6)	0.0061 (7)	−0.0018 (7)
C12	0.0210 (8)	0.0168 (8)	0.0207 (9)	0.0009 (6)	0.0040 (7)	0.0011 (7)
C13	0.0208 (8)	0.0193 (8)	0.0184 (8)	−0.0015 (6)	0.0053 (6)	−0.0020 (7)
C14	0.0206 (8)	0.0191 (9)	0.0173 (8)	−0.0012 (6)	0.0042 (6)	−0.0010 (7)
C15	0.0184 (7)	0.0183 (8)	0.0213 (8)	−0.0014 (6)	0.0045 (6)	−0.0004 (7)
C16	0.0273 (9)	0.0232 (9)	0.0247 (9)	0.0001 (7)	0.0026 (7)	0.0051 (8)
C17	0.0222 (8)	0.0183 (9)	0.0342 (10)	0.0006 (7)	0.0017 (7)	0.0025 (8)
C18	0.0226 (8)	0.0187 (8)	0.0326 (10)	0.0020 (7)	0.0062 (7)	−0.0028 (8)
C19	0.0212 (8)	0.0287 (10)	0.0175 (8)	0.0046 (7)	0.0071 (7)	0.0034 (7)
C20	0.0258 (9)	0.0285 (10)	0.0230 (9)	0.0068 (7)	0.0110 (7)	0.0074 (8)
C21	0.0293 (9)	0.0401 (12)	0.0220 (9)	0.0123 (8)	0.0078 (8)	0.0075 (8)
C22	0.0267 (10)	0.0491 (13)	0.0226 (9)	0.0051 (9)	0.0027 (8)	0.0023 (9)
C23	0.0277 (9)	0.0385 (12)	0.0239 (10)	−0.0031 (8)	0.0033 (7)	−0.0014 (9)
C24	0.0260 (9)	0.0296 (10)	0.0182 (9)	0.0025 (7)	0.0046 (7)	0.0007 (7)
C25	0.0388 (12)	0.0261 (11)	0.0796 (19)	0.0088 (9)	0.0140 (12)	0.0183 (12)
C26	0.0282 (9)	0.0229 (9)	0.0206 (9)	0.0027 (7)	0.0132 (7)	0.0016 (7)
C27	0.0274 (9)	0.0297 (11)	0.0422 (12)	−0.0023 (8)	0.0163 (9)	−0.0050 (9)

Geometric parameters (Å, º) top

S1—O1	1.4324 (14)	C7—C9	1.537 (3)
S1—O2	1.4365 (14)	C8—H8A	0.9800
S1—N1	1.6455 (15)	C8—H8B	0.9800
S1—C1	1.757 (2)	C8—H8C	0.9800
O3—C12	1.372 (2)	C9—H9A	0.9800
O3—C19	1.400 (2)	C9—H9B	0.9800
O4—C20	1.369 (2)	C9—H9C	0.9800
O4—C25	1.427 (2)	C10—H10A	0.9800
O5—C13	1.338 (2)	C10—H10B	0.9800
O5—C26	1.450 (2)	C10—H10C	0.9800
O6—C27	1.425 (2)	C11—C12	1.400 (2)
O6—H6	0.8400	C12—C13	1.392 (2)
O1W—H1W	0.795 (16)	C14—C15	1.501 (2)
O1W—H2W	0.805 (16)	C16—C17	1.378 (3)
N1—C11	1.376 (2)	C16—H16A	0.9500
N1—H1A	0.8800	C17—C18	1.383 (3)
N2—C14	1.333 (2)	C17—H17A	0.9500
N2—C11	1.338 (2)	C18—H18A	0.9500
N3—C13	1.331 (2)	C19—C24	1.373 (3)
N3—C14	1.333 (2)	C19—C20	1.398 (3)
N4—C16	1.338 (2)	C20—C21	1.396 (3)
N4—C15	1.339 (2)	C21—C22	1.387 (3)
N5—C15	1.329 (2)	C21—H21A	0.9500
N5—C18	1.337 (2)	C22—C23	1.376 (3)
C1—C6	1.386 (3)	C22—H22A	0.9500
C1—C2	1.386 (3)	C23—C24	1.401 (3)
C2—C3	1.392 (3)	C23—H23A	0.9500
C2—H2A	0.9500	C24—H24A	0.9500
C3—C4	1.395 (3)	C25—H25A	0.9800
C3—H3A	0.9500	C25—H25B	0.9800
C4—C5	1.391 (3)	C25—H25C	0.9800
C4—C7	1.536 (3)	C26—C27	1.499 (3)
C5—C6	1.381 (3)	C26—H26A	0.9900
C5—H5A	0.9500	C26—H26B	0.9900
C6—H6A	0.9500	C27—H27A	0.9900
C7—C10	1.520 (3)	C27—H27B	0.9900
C7—C8	1.520 (3)

O1—S1—O2	119.06 (9)	N2—C11—N1	118.65 (15)
O1—S1—N1	110.81 (8)	N2—C11—C12	121.54 (16)
O2—S1—N1	102.75 (8)	N1—C11—C12	119.81 (17)
O1—S1—C1	109.13 (9)	O3—C12—C13	123.34 (16)
O2—S1—C1	108.18 (9)	O3—C12—C11	119.96 (16)
N1—S1—C1	106.09 (9)	C13—C12—C11	116.46 (16)
C12—O3—C19	117.36 (14)	N3—C13—O5	121.38 (15)
C20—O4—C25	116.32 (16)	N3—C13—C12	122.68 (16)
C13—O5—C26	118.20 (14)	O5—C13—C12	115.93 (16)
C27—O6—H6	109.5	N2—C14—N3	127.63 (17)
H1W—O1W—H2W	110 (2)	N2—C14—C15	115.81 (15)
C11—N1—S1	125.60 (13)	N3—C14—C15	116.56 (15)
C11—N1—H1A	117.2	N5—C15—N4	126.42 (17)
S1—N1—H1A	117.2	N5—C15—C14	116.86 (16)
C14—N2—C11	116.05 (15)	N4—C15—C14	116.71 (15)
C13—N3—C14	115.46 (15)	N4—C16—C17	122.46 (18)
C16—N4—C15	115.93 (16)	N4—C16—H16A	118.8
C15—N5—C18	116.21 (16)	C17—C16—H16A	118.8
C6—C1—C2	120.54 (18)	C16—C17—C18	116.55 (17)
C6—C1—S1	118.11 (15)	C16—C17—H17A	121.7
C2—C1—S1	121.29 (15)	C18—C17—H17A	121.7
C1—C2—C3	119.15 (17)	N5—C18—C17	122.32 (17)
C1—C2—H2A	120.4	N5—C18—H18A	118.8
C3—C2—H2A	120.4	C17—C18—H18A	118.8
C2—C3—C4	121.41 (18)	C24—C19—C20	120.89 (18)
C2—C3—H3A	119.3	C24—C19—O3	123.86 (17)
C4—C3—H3A	119.3	C20—C19—O3	115.26 (17)
C5—C4—C3	117.74 (19)	O4—C20—C21	124.53 (18)
C5—C4—C7	119.46 (18)	O4—C20—C19	116.62 (17)
C3—C4—C7	122.81 (19)	C21—C20—C19	118.85 (19)
C6—C5—C4	121.77 (19)	C22—C21—C20	120.29 (19)
C6—C5—H5A	119.1	C22—C21—H21A	119.9
C4—C5—H5A	119.1	C20—C21—H21A	119.9
C5—C6—C1	119.39 (19)	C23—C22—C21	120.24 (19)
C5—C6—H6A	120.3	C23—C22—H22A	119.9
C1—C6—H6A	120.3	C21—C22—H22A	119.9
C10—C7—C8	109.1 (2)	C22—C23—C24	120.1 (2)
C10—C7—C4	109.08 (18)	C22—C23—H23A	120.0
C8—C7—C4	112.58 (18)	C24—C23—H23A	120.0
C10—C7—C9	109.1 (2)	C19—C24—C23	119.65 (19)
C8—C7—C9	108.1 (2)	C19—C24—H24A	120.2
C4—C7—C9	108.85 (18)	C23—C24—H24A	120.2
C7—C8—H8A	109.5	O4—C25—H25A	109.5
C7—C8—H8B	109.5	O4—C25—H25B	109.5
H8A—C8—H8B	109.5	H25A—C25—H25B	109.5
C7—C8—H8C	109.5	O4—C25—H25C	109.5
H8A—C8—H8C	109.5	H25A—C25—H25C	109.5
H8B—C8—H8C	109.5	H25B—C25—H25C	109.5
C7—C9—H9A	109.5	O5—C26—C27	109.51 (15)
C7—C9—H9B	109.5	O5—C26—H26A	109.8
H9A—C9—H9B	109.5	C27—C26—H26A	109.8
C7—C9—H9C	109.5	O5—C26—H26B	109.8
H9A—C9—H9C	109.5	C27—C26—H26B	109.8
H9B—C9—H9C	109.5	H26A—C26—H26B	108.2
C7—C10—H10A	109.5	O6—C27—C26	111.16 (16)
C7—C10—H10B	109.5	O6—C27—H27A	109.4
H10A—C10—H10B	109.5	C26—C27—H27A	109.4
C7—C10—H10C	109.5	O6—C27—H27B	109.4
H10A—C10—H10C	109.5	C26—C27—H27B	109.4
H10B—C10—H10C	109.5	H27A—C27—H27B	108.0

O1—S1—N1—C11	47.22 (18)	C26—O5—C13—C12	−165.22 (15)
O2—S1—N1—C11	175.43 (16)	O3—C12—C13—N3	178.87 (16)
C1—S1—N1—C11	−71.10 (18)	C11—C12—C13—N3	4.5 (3)
O1—S1—C1—C6	150.77 (16)	O3—C12—C13—O5	−0.3 (3)
O2—S1—C1—C6	19.86 (18)	C11—C12—C13—O5	−174.61 (16)
N1—S1—C1—C6	−89.80 (17)	C11—N2—C14—N3	0.7 (3)
O1—S1—C1—C2	−26.27 (17)	C11—N2—C14—C15	−178.84 (15)
O2—S1—C1—C2	−157.18 (15)	C13—N3—C14—N2	−1.2 (3)
N1—S1—C1—C2	93.16 (16)	C13—N3—C14—C15	178.36 (15)
C6—C1—C2—C3	−0.3 (3)	C18—N5—C15—N4	1.6 (3)
S1—C1—C2—C3	176.65 (13)	C18—N5—C15—C14	−177.86 (15)
C1—C2—C3—C4	0.9 (3)	C16—N4—C15—N5	−2.9 (3)
C2—C3—C4—C5	−0.4 (3)	C16—N4—C15—C14	176.55 (15)
C2—C3—C4—C7	179.51 (17)	N2—C14—C15—N5	26.1 (2)
C3—C4—C5—C6	−0.7 (3)	N3—C14—C15—N5	−153.49 (16)
C7—C4—C5—C6	179.4 (2)	N2—C14—C15—N4	−153.35 (16)
C4—C5—C6—C1	1.2 (4)	N3—C14—C15—N4	27.0 (2)
C2—C1—C6—C5	−0.7 (3)	C15—N4—C16—C17	1.1 (3)
S1—C1—C6—C5	−177.78 (18)	N4—C16—C17—C18	1.7 (3)
C5—C4—C7—C10	−55.2 (3)	C15—N5—C18—C17	1.6 (3)
C3—C4—C7—C10	124.9 (2)	C16—C17—C18—N5	−3.1 (3)
C5—C4—C7—C8	−176.5 (2)	C12—O3—C19—C24	2.1 (2)
C3—C4—C7—C8	3.7 (3)	C12—O3—C19—C20	−177.61 (15)
C5—C4—C7—C9	63.8 (3)	C25—O4—C20—C21	−15.3 (3)
C3—C4—C7—C9	−116.1 (2)	C25—O4—C20—C19	165.06 (19)
C14—N2—C11—N1	−177.91 (16)	C24—C19—C20—O4	−179.91 (16)
C14—N2—C11—C12	2.5 (3)	O3—C19—C20—O4	−0.2 (2)
S1—N1—C11—N2	2.0 (3)	C24—C19—C20—C21	0.4 (3)
S1—N1—C11—C12	−178.44 (14)	O3—C19—C20—C21	−179.89 (15)
C19—O3—C12—C13	68.0 (2)	O4—C20—C21—C22	−179.81 (18)
C19—O3—C12—C11	−117.88 (18)	C19—C20—C21—C22	−0.2 (3)
N2—C11—C12—O3	−179.54 (16)	C20—C21—C22—C23	0.1 (3)
N1—C11—C12—O3	0.9 (3)	C21—C22—C23—C24	−0.2 (3)
N2—C11—C12—C13	−5.0 (3)	C20—C19—C24—C23	−0.5 (3)
N1—C11—C12—C13	175.48 (16)	O3—C19—C24—C23	179.80 (16)
C14—N3—C13—O5	177.48 (16)	C22—C23—C24—C19	0.4 (3)
C14—N3—C13—C12	−1.6 (3)	C13—O5—C26—C27	90.58 (19)
C26—O5—C13—N3	15.6 (2)	O5—C26—C27—O6	−65.8 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O6—H6···N3ⁱ	0.84	2.51	3.317 (2)	162
O6—H6···N4ⁱ	0.84	2.60	3.141 (2)	124
O1W—H1W···O4	0.80 (2)	2.30 (2)	3.013 (2)	150 (3)
O1W—H2W···N4ⁱⁱ	0.81 (2)	2.07 (2)	2.873 (2)	174 (3)
N1—H1A···O1W	0.88	1.87	2.721 (2)	163

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

Experimental details

Crystal data
Chemical formula	C₂₇H₂₉N₅O₆S·H₂O
M_r	569.63
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	123
a, b, c (Å)	12.3393 (4), 15.1238 (6), 14.6988 (4)
β (°)	95.037 (3)
V (Å³)	2732.46 (16)
Z	4
Radiation type	Cu Kα
µ (mm⁻¹)	1.52
Crystal size (mm)	0.79 × 0.43 × 0.22

Data collection
Diffractometer	Agilent Xcalibur (Ruby, Gemini)
Absorption correction	Analytical (CrysAlis PRO; Agilent, 2012)
T_min, T_max	0.535, 0.766
No. of measured, independent and observed [I > 2σ(I)] reflections	9563, 9563, 7477
R_int	0.000
(sin θ/λ)_max (Å⁻¹)	0.630

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.055, 0.163, 1.03
No. of reflections	9563
No. of parameters	373
No. of restraints	3
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.44, −0.77

Computer programs: CrysAlis PRO (Agilent, 2012), CrysAlis RED (Agilent, 2012), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O6—H6···N3ⁱ	0.84	2.51	3.317 (2)	162
O6—H6···N4ⁱ	0.84	2.60	3.141 (2)	124
O1W—H1W···O4	0.795 (16)	2.297 (19)	3.013 (2)	150 (3)
O1W—H2W···N4ⁱⁱ	0.805 (16)	2.071 (16)	2.873 (2)	174 (3)
N1—H1A···O1W	0.88	1.87	2.721 (2)	163

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

Acknowledgements

MK thanks the UOM for research facilities. RJB acknowledges the NSF–MRI program (grant No. CHE-0619278) for funds to purchase the X-ray diffractometer.

References

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