Eprosartan mesylate, an angiotensin II receptor antagonist.

The title compound, eprosartan mesylate {systematic name: 2-butyl-1-(4-carb-oxy-benz-yl)-5-[(E)-2-carb-oxy-3-(thio-phen-2-yl)prop-1-en-yl]-1H-imidazol-3-ium methane-sulfonate}, C(23)H(25)N(2)O(4)S(+)·CH(3)O(3)S(-), one of the angiotensin II-receptor antagonists, is effective in regulating hypertension, induced or exacerbated by angiotensin II, and in the treatment of congestive heart failure, renal failure and glaucoma. In the eprosartan residue, which appears in this crystal in the cationic imidazolium form, the benzene ring plane is almost orthogonal to that of the imidazole ring, making a dihedral angle of 87.89 (2)°. The thio-phene ring forms dihedral angles of 66.54 (2) and 67.12 (2)° with the benzene and imidazole rings, respectively. The imidazolium NH group and the H atom of the aromatic carboxyl group participate in hydrogen bonds with the the O atoms of the anion, thus forming centrosymmetric aggregates made up of two cations and two anions each. The second carboxyl group further links the above-mentioned aggregates through a conventional centrosymmetric hydrogen-bonding motif into infinite chains along [011].

Related literature

For applications of eprosartan mesylate in medicine, see: Punzi & Punzi (2005 ▶); Punzi et al. (2004 ▶); Hillaert et al. (2003 ▶). For the crystal structures of other eprosartan derivatives, see: Wu et al. (2009 ▶); Sheng et al. (1999 ▶). For the preparation of eprosartan mesylate, see Bandi et al. (2010 ▶).

Experimental

Crystal data

C23H25N2O4S+·CH3O3S−

M = 520.60

Triclinic,

a = 8.6635 (4) Å

b = 12.6935 (7) Å

c = 13.6679 (8) Å

α = 112.700 (2)°

β = 101.386 (1)°

γ = 96.718 (1)°

V = 1327.97 (12) Å3

Z = 2

Mo Kα radiation

μ = 0.25 mm−1

T = 193 K

0.48 × 0.34 × 0.16 mm

Data collection

Rigaku R-AXIS-RAPID/ZJUG diffractometer

Absorption correction: multi-scan (ABSCOR; Higashi, 1995 ▶) T min = 0.879, T max = 0.961

10590 measured reflections

4689 independent reflections

3248 reflections with I > 2σ(I)

R int = 0.022

Refinement

R[F 2 > 2σ(F 2)] = 0.083

wR(F 2) = 0.225

S = 0.99

4689 reflections

318 parameters

12 restraints

H-atom parameters constrained

Δρmax = 1.35 e Å−3

Δρmin = −0.62 e Å−3

Data collection: PROCESS-AUTO (Rigaku, 2006 ▶); cell refinement: PROCESS-AUTO; data reduction: CrystalStructure (Rigaku, 2007 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811006659/ya2135sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811006659/ya2135Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C23H25N2O4S+·CH3O3S−	Z = 2
Mr = 520.60	F(000) = 548
Triclinic, P1	Dx = 1.302 Mg m−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 8.6635 (4) Å	Cell parameters from 8503 reflections
b = 12.6935 (7) Å	θ = 3.0–27.4°
c = 13.6679 (8) Å	µ = 0.25 mm−1
α = 112.700 (2)°	T = 193 K
β = 101.386 (1)°	Platelet, colorless
γ = 96.718 (1)°	0.48 × 0.34 × 0.16 mm
V = 1327.97 (12) Å3

Rigaku R-AXIS-RAPID/ZJUG diffractometer	4689 independent reflections
Radiation source: rotating anode	3248 reflections with I > 2σ(I)
graphite	Rint = 0.022
Detector resolution: 10.00 pixels mm-1	θmax = 25.0°, θmin = 3.0°
ω scans	h = −9→10
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)	k = −15→14
Tmin = 0.879, Tmax = 0.961	l = −16→16
10590 measured reflections

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)] = 0.083	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.225	H-atom parameters constrained
S = 0.99	w = 1/[σ2(Fo2) + (0.0839P)2 + 3.6024P] where P = (Fo2 + 2Fc2)/3
4689 reflections	(Δ/σ)max = 0.001
318 parameters	Δρmax = 1.35 e Å−3
12 restraints	Δρmin = −0.62 e Å−3

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.

	x	y	z	Uiso*/Ueq
O2	0.4103 (5)	0.4459 (4)	0.8655 (3)	0.0774 (12)
O7	1.0612 (4)	0.4213 (4)	0.3064 (4)	0.0925 (14)
O5	0.7861 (5)	0.4244 (5)	0.3127 (4)	0.0928 (14)
O6	0.8704 (7)	0.2450 (4)	0.2308 (5)	0.1191 (19)
C24	0.8490 (8)	0.3725 (6)	0.1275 (5)	0.0821 (17)
H24A	0.7348	0.3368	0.0906	0.123*
H24B	0.9153	0.3287	0.0829	0.123*
H24C	0.8707	0.4537	0.1366	0.123*
O4	0.3022 (10)	−0.1534 (7)	0.6016 (7)	0.165 (3)
S2	0.89587 (14)	0.36913 (11)	0.25638 (10)	0.0517 (4)
S1	0.9345 (2)	0.2510 (2)	0.84615 (15)	0.0991 (7)
N1	0.3712 (4)	0.3219 (3)	0.4681 (3)	0.0437 (8)
N2	0.5741 (4)	0.3570 (3)	0.4086 (3)	0.0449 (8)
H2A	0.6329	0.3611	0.3640	0.054*
O1	0.6716 (4)	0.4864 (4)	0.9480 (3)	0.0751 (11)
H1	0.6375	0.5105	1.0044	0.113*
C1	0.5038 (5)	0.3802 (4)	0.5597 (3)	0.0431 (10)
C3	0.4180 (5)	0.3063 (4)	0.3763 (3)	0.0443 (10)
C2	0.6297 (5)	0.4018 (4)	0.5203 (3)	0.0450 (10)
H2	0.7370	0.4409	0.5625	0.054*
O3	0.1466 (5)	−0.0801 (4)	0.7013 (4)	0.0770 (11)
H3	0.1472	−0.1412	0.7116	0.116*
C4	0.4876 (5)	0.4100 (4)	0.6710 (3)	0.0473 (10)
H4	0.3906	0.4325	0.6850	0.057*
C12	0.2101 (5)	0.2783 (4)	0.4736 (4)	0.0511 (11)
H12A	0.1341	0.2465	0.3995	0.061*
H12B	0.1716	0.3436	0.5233	0.061*
C5	0.5937 (6)	0.4090 (4)	0.7544 (4)	0.0499 (11)
C15	0.1446 (6)	0.0995 (4)	0.6343 (4)	0.0561 (12)
H15	0.0945	0.1024	0.6910	0.067*
C13	0.2129 (5)	0.1834 (4)	0.5152 (4)	0.0463 (10)
C6	0.5533 (6)	0.4495 (5)	0.8623 (4)	0.0552 (12)
C14	0.1433 (6)	0.1868 (4)	0.5977 (4)	0.0553 (12)
H14	0.0936	0.2498	0.6301	0.066*
C7	0.7515 (6)	0.3701 (5)	0.7518 (4)	0.0636 (14)
H7A	0.7659	0.3455	0.6766	0.076*
H7B	0.8415	0.4365	0.8025	0.076*
C17	0.2873 (7)	0.0043 (5)	0.5060 (5)	0.0708 (15)
H17	0.3372	−0.0585	0.4737	0.085*
C9	0.6218 (6)	0.1805 (4)	0.7697 (4)	0.0523 (11)
H9	0.5112	0.1735	0.7374	0.063*
C8	0.7559 (7)	0.2699 (5)	0.7850 (4)	0.0625 (14)
C16	0.2179 (6)	0.0083 (4)	0.5895 (4)	0.0547 (11)
C18	0.2848 (7)	0.0905 (4)	0.4692 (5)	0.0649 (14)
H18	0.3328	0.0867	0.4115	0.078*
C20	0.3160 (6)	0.2441 (5)	0.2616 (4)	0.0629 (13)
H20A	0.2265	0.2843	0.2530	0.075*
H20B	0.2678	0.1640	0.2497	0.075*
C19	0.2231 (8)	−0.0823 (5)	0.6307 (6)	0.0813 (18)
C10	0.6885 (12)	0.1052 (6)	0.8128 (6)	0.100 (2)
H10	0.6227	0.0400	0.8130	0.120*
C22	0.2867 (9)	0.1741 (8)	0.0603 (5)	0.114 (3)
H22A	0.1978	0.2157	0.0554	0.137*
H22B	0.2389	0.0937	0.0480	0.137*
C21	0.3989 (7)	0.2353 (6)	0.1744 (4)	0.0809 (17)
H21A	0.4492	0.3149	0.1863	0.097*
H21B	0.4860	0.1923	0.1804	0.097*
C11	0.8466 (12)	0.1306 (7)	0.8526 (6)	0.103 (2)
H11	0.9040	0.0853	0.8817	0.123*
C23	0.3652 (14)	0.1675 (11)	−0.0273 (10)	0.167 (4)
H23A	0.2858	0.1265	−0.0990	0.251*
H23B	0.4520	0.1248	−0.0243	0.251*
H23C	0.4102	0.2466	−0.0171	0.251*

	U11	U22	U33	U12	U13	U23
O2	0.070 (2)	0.131 (3)	0.049 (2)	0.048 (2)	0.0280 (18)	0.042 (2)
O7	0.048 (2)	0.137 (4)	0.085 (3)	0.002 (2)	0.006 (2)	0.049 (3)
O5	0.091 (3)	0.141 (4)	0.088 (3)	0.056 (3)	0.056 (2)	0.066 (3)
O6	0.170 (5)	0.078 (3)	0.125 (4)	0.013 (3)	0.024 (4)	0.071 (3)
C24	0.096 (4)	0.108 (5)	0.060 (3)	0.030 (4)	0.025 (3)	0.049 (3)
O4	0.186 (4)	0.158 (3)	0.180 (4)	0.050 (3)	0.067 (3)	0.089 (3)
S2	0.0486 (7)	0.0683 (8)	0.0548 (7)	0.0151 (6)	0.0172 (5)	0.0407 (6)
S1	0.0965 (13)	0.1373 (17)	0.0840 (12)	0.0633 (12)	0.0275 (10)	0.0554 (12)
N1	0.046 (2)	0.054 (2)	0.043 (2)	0.0174 (17)	0.0175 (16)	0.0288 (17)
N2	0.049 (2)	0.057 (2)	0.0415 (19)	0.0199 (17)	0.0198 (16)	0.0274 (17)
O1	0.073 (2)	0.110 (3)	0.0413 (19)	0.031 (2)	0.0161 (18)	0.028 (2)
C1	0.050 (2)	0.048 (2)	0.039 (2)	0.018 (2)	0.0169 (19)	0.0216 (19)
C3	0.050 (2)	0.051 (2)	0.041 (2)	0.019 (2)	0.0165 (19)	0.025 (2)
C2	0.051 (2)	0.050 (2)	0.038 (2)	0.016 (2)	0.0135 (19)	0.0209 (19)
O3	0.090 (3)	0.078 (3)	0.084 (3)	0.020 (2)	0.028 (2)	0.053 (2)
C4	0.055 (3)	0.054 (3)	0.042 (2)	0.022 (2)	0.019 (2)	0.025 (2)
C12	0.046 (2)	0.064 (3)	0.056 (3)	0.016 (2)	0.018 (2)	0.036 (2)
C5	0.056 (3)	0.060 (3)	0.046 (3)	0.022 (2)	0.021 (2)	0.029 (2)
C15	0.062 (3)	0.063 (3)	0.056 (3)	0.016 (2)	0.028 (2)	0.032 (2)
C13	0.041 (2)	0.054 (3)	0.047 (2)	0.009 (2)	0.0128 (19)	0.024 (2)
C6	0.065 (3)	0.072 (3)	0.044 (3)	0.030 (3)	0.022 (2)	0.033 (2)
C14	0.063 (3)	0.058 (3)	0.061 (3)	0.026 (2)	0.031 (2)	0.031 (2)
C7	0.061 (3)	0.095 (4)	0.058 (3)	0.032 (3)	0.027 (2)	0.046 (3)
C17	0.084 (4)	0.059 (3)	0.091 (4)	0.031 (3)	0.052 (3)	0.035 (3)
C9	0.064 (3)	0.049 (3)	0.052 (3)	0.022 (2)	0.019 (2)	0.026 (2)
C8	0.077 (3)	0.088 (4)	0.040 (3)	0.047 (3)	0.028 (2)	0.032 (3)
C16	0.054 (3)	0.048 (3)	0.066 (3)	0.011 (2)	0.019 (2)	0.027 (2)
C18	0.078 (4)	0.063 (3)	0.072 (3)	0.024 (3)	0.045 (3)	0.033 (3)
C20	0.060 (3)	0.085 (4)	0.041 (3)	0.016 (3)	0.011 (2)	0.026 (3)
C19	0.095 (4)	0.062 (3)	0.118 (5)	0.044 (3)	0.055 (4)	0.049 (4)
C10	0.137 (7)	0.075 (4)	0.093 (5)	0.026 (5)	0.044 (5)	0.033 (4)
C22	0.103 (5)	0.170 (8)	0.045 (3)	0.005 (5)	0.016 (3)	0.029 (4)
C21	0.082 (4)	0.104 (5)	0.045 (3)	0.008 (3)	0.014 (3)	0.024 (3)
C11	0.151 (7)	0.104 (5)	0.089 (5)	0.075 (6)	0.044 (5)	0.060 (4)
C23	0.168 (5)	0.173 (5)	0.158 (5)	0.032 (3)	0.045 (3)	0.067 (3)

O2—C6	1.245 (6)	C15—C16	1.378 (7)
O7—S2	1.414 (4)	C15—C14	1.381 (6)
O5—S2	1.421 (4)	C15—H15	0.9500
O6—S2	1.455 (4)	C13—C14	1.370 (6)
C24—S2	1.747 (5)	C13—C18	1.388 (7)
C24—H24A	0.9800	C14—H14	0.9500
C24—H24B	0.9800	C7—C8	1.509 (7)
C24—H24C	0.9800	C7—H7A	0.9900
O4—C19	1.191 (8)	C7—H7B	0.9900
S1—C11	1.668 (8)	C17—C18	1.369 (7)
S1—C8	1.698 (5)	C17—C16	1.378 (7)
N1—C3	1.343 (5)	C17—H17	0.9500
N1—C1	1.398 (5)	C9—C10	1.423 (9)
N1—C12	1.468 (5)	C9—C8	1.448 (7)
N2—C3	1.334 (5)	C9—H9	0.9500
N2—C2	1.365 (5)	C16—C19	1.465 (7)
N2—H2A	0.8800	C18—H18	0.9500
O1—C6	1.277 (6)	C20—C21	1.484 (7)
O1—H1	0.8400	C20—H20A	0.9900
C1—C2	1.353 (6)	C20—H20B	0.9900
C1—C4	1.459 (6)	C10—C11	1.320 (10)
C3—C20	1.482 (6)	C10—H10	0.9500
C2—H2	0.9500	C22—C21	1.506 (8)
O3—C19	1.268 (7)	C22—C23	1.470 (12)
O3—H3	0.8400	C22—H22A	0.9900
C4—C5	1.320 (6)	C22—H22B	0.9900
C4—H4	0.9500	C21—H21A	0.9900
C12—C13	1.518 (6)	C21—H21B	0.9900
C12—H12A	0.9900	C11—H11	0.9500
C12—H12B	0.9900	C23—H23A	0.9800
C5—C6	1.491 (6)	C23—H23B	0.9800
C5—C7	1.509 (6)	C23—H23C	0.9800
S2—C24—H24A	109.5	C8—C7—C5	111.0 (4)
S2—C24—H24B	109.5	C8—C7—H7A	109.4
H24A—C24—H24B	109.5	C5—C7—H7A	109.4
S2—C24—H24C	109.5	C8—C7—H7B	109.4
H24A—C24—H24C	109.5	C5—C7—H7B	109.4
H24B—C24—H24C	109.5	H7A—C7—H7B	108.0
O7—S2—O5	116.2 (3)	C18—C17—C16	120.4 (5)
O7—S2—O6	109.4 (3)	C18—C17—H17	119.8
O5—S2—O6	112.5 (3)	C16—C17—H17	119.8
O7—S2—C24	107.5 (3)	C10—C9—C8	106.3 (5)
O5—S2—C24	106.6 (3)	C10—C9—H9	126.9
O6—S2—C24	103.8 (3)	C8—C9—H9	126.9
C11—S1—C8	92.4 (4)	C9—C8—C7	127.8 (4)
C3—N1—C1	109.3 (3)	C9—C8—S1	112.1 (4)
C3—N1—C12	126.4 (4)	C7—C8—S1	120.0 (4)
C1—N1—C12	124.1 (3)	C15—C16—C17	119.0 (4)
C3—N2—C2	110.5 (3)	C15—C16—C19	120.4 (5)
C3—N2—H2A	124.7	C17—C16—C19	120.7 (5)
C2—N2—H2A	124.7	C17—C18—C13	120.9 (5)
C6—O1—H1	109.5	C17—C18—H18	119.6
C2—C1—N1	106.1 (4)	C13—C18—H18	119.6
C2—C1—C4	132.7 (4)	C3—C20—C21	115.9 (4)
N1—C1—C4	121.2 (4)	C3—C20—H20A	108.3
N2—C3—N1	106.7 (4)	C21—C20—H20A	108.3
N2—C3—C20	126.8 (4)	C3—C20—H20B	108.3
N1—C3—C20	126.6 (4)	C21—C20—H20B	108.3
C1—C2—N2	107.3 (4)	H20A—C20—H20B	107.4
C1—C2—H2	126.3	O4—C19—O3	121.1 (7)
N2—C2—H2	126.3	O4—C19—C16	120.6 (7)
C19—O3—H3	109.5	O3—C19—C16	118.3 (5)
C5—C4—C1	126.8 (4)	C11—C10—C9	116.6 (7)
C5—C4—H4	116.6	C11—C10—H10	121.7
C1—C4—H4	116.6	C9—C10—H10	121.7
N1—C12—C13	110.8 (3)	C21—C22—C23	113.8 (7)
N1—C12—H12A	109.5	C21—C22—H22A	108.8
C13—C12—H12A	109.5	C23—C22—H22A	108.8
N1—C12—H12B	109.5	C21—C22—H22B	108.8
C13—C12—H12B	109.5	C23—C22—H22B	108.8
H12A—C12—H12B	108.1	H22A—C22—H22B	107.7
C4—C5—C6	116.9 (4)	C22—C21—C20	112.9 (5)
C4—C5—C7	126.8 (4)	C22—C21—H21A	109.0
C6—C5—C7	116.4 (4)	C20—C21—H21A	109.0
C16—C15—C14	120.5 (4)	C22—C21—H21B	109.0
C16—C15—H15	119.7	C20—C21—H21B	109.0
C14—C15—H15	119.7	H21A—C21—H21B	107.8
C14—C13—C18	118.6 (4)	C10—C11—S1	112.7 (6)
C14—C13—C12	120.9 (4)	C10—C11—H11	123.7
C18—C13—C12	120.5 (4)	S1—C11—H11	123.7
O2—C6—O1	123.5 (4)	C22—C23—H23A	109.5
O2—C6—C5	120.0 (4)	C22—C23—H23B	109.5
O1—C6—C5	116.5 (4)	H23A—C23—H23B	109.5
C13—C14—C15	120.6 (4)	C22—C23—H23C	109.5
C13—C14—H14	119.7	H23A—C23—H23C	109.5
C15—C14—H14	119.7	H23B—C23—H23C	109.5
C3—N1—C1—C2	1.7 (5)	C16—C15—C14—C13	0.9 (8)
C12—N1—C1—C2	177.7 (4)	C4—C5—C7—C8	−120.2 (5)
C3—N1—C1—C4	179.3 (4)	C6—C5—C7—C8	59.3 (6)
C12—N1—C1—C4	−4.7 (6)	C10—C9—C8—C7	178.9 (5)
C2—N2—C3—N1	2.1 (5)	C10—C9—C8—S1	0.0 (5)
C2—N2—C3—C20	−177.6 (4)	C5—C7—C8—C9	30.1 (7)
C1—N1—C3—N2	−2.3 (5)	C5—C7—C8—S1	−151.1 (4)
C12—N1—C3—N2	−178.2 (4)	C11—S1—C8—C9	0.7 (4)
C1—N1—C3—C20	177.3 (4)	C11—S1—C8—C7	−178.3 (4)
C12—N1—C3—C20	1.5 (7)	C14—C15—C16—C17	−1.2 (8)
N1—C1—C2—N2	−0.4 (5)	C14—C15—C16—C19	178.2 (5)
C4—C1—C2—N2	−177.6 (4)	C18—C17—C16—C15	0.7 (9)
C3—N2—C2—C1	−1.1 (5)	C18—C17—C16—C19	−178.7 (6)
C2—C1—C4—C5	−39.5 (8)	C16—C17—C18—C13	0.2 (9)
N1—C1—C4—C5	143.6 (5)	C14—C13—C18—C17	−0.5 (8)
C3—N1—C12—C13	111.2 (5)	C12—C13—C18—C17	−179.7 (5)
C1—N1—C12—C13	−64.1 (5)	N2—C3—C20—C21	1.8 (8)
C1—C4—C5—C6	176.7 (4)	N1—C3—C20—C21	−177.8 (5)
C1—C4—C5—C7	−3.8 (8)	C15—C16—C19—O4	−171.1 (7)
N1—C12—C13—C14	131.3 (5)	C17—C16—C19—O4	8.3 (11)
N1—C12—C13—C18	−49.5 (6)	C15—C16—C19—O3	6.2 (9)
C4—C5—C6—O2	23.4 (7)	C17—C16—C19—O3	−174.4 (6)
C7—C5—C6—O2	−156.2 (5)	C8—C9—C10—C11	−1.0 (8)
C4—C5—C6—O1	−156.8 (5)	C23—C22—C21—C20	178.2 (8)
C7—C5—C6—O1	23.6 (7)	C3—C20—C21—C22	−178.4 (6)
C18—C13—C14—C15	0.0 (7)	C9—C10—C11—S1	1.6 (9)
C12—C13—C14—C15	179.2 (4)	C8—S1—C11—C10	−1.3 (6)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···O5	0.88	1.86	2.697 (5)	158
O1—H1···O2i	0.84	1.80	2.628 (5)	171
O3—H3···O6ii	0.84	1.78	2.597 (5)	162

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2A⋯O5	0.88	1.86	2.697 (5)	158
O1—H1⋯O2i	0.84	1.80	2.628 (5)	171
O3—H3⋯O6ii	0.84	1.78	2.597 (5)	162

Symmetry codes: (i) ; (ii) .