Almotriptan, an anti­migraine agent, and its malate salt

The crystal structures of almotriptan {systematic name: N,N-dimethyl-2-[5-(pyrrolidin-1-ylsulfonyl­meth­yl)-1H-indol-3-yl]­ethanamine}, C₁₇H₂₅N₃O₂S, and almotriptan malate {systematic name: N,N-dimethyl-2-[5-(pyrrolidin-1-ylsulfonyl­meth­yl)-1H-indol-3-yl]ethanaminium malate, C₁₇H₂₆N₃O₂S⁺·C₄H₅O₅⁻, a novel selective serotonin 1B/D agonist, have been determined in order to gain further insight into the structure–activity relationships of triptans. The two structures differ in the orientation of their sulfonyl­pyrrolidine side chains. A comparison with other triptans reveals that mol­ecules of almotriptan, sumatriptan, zolmitriptan and rizatriptan can adopt two principal conformations. N—H...N, N—H...O and O—H...O hydrogen bonds are responsible for the mol­ecular packing.

S1. Comment

Triptans are the first class of drugs designed to relieve migraine symptoms by targeting the disease pathology (Perry & Markham, 1998; Humphrey et al., 1990). Unlike nonspecific medications that increase a patient's tolerance to pain, nausea and associated symptoms, triptans act specifically via receptor-mediated binding in the central nervous system and its vascular system. Triptan medications are selective 5-hydroxytryptamine (5-HT_1B/D) receptor agonists that share a basic indole ring structure with different side chains. Almotriptan, (I), is a novel, selective serotonin 1B/D agonist, developed for the abortive treatment of migraine (De Vries et al., 1999). Over the past decade, seven triptans have become available in the USA, viz. sumatriptan, zolmitriptan, naratriptan, rizatriptan, frovatriptan, eletriptan and almotriptan. They are believed to constrict the blood vessels by acting on the 5-HT_1B/D receptors, which makes them the best amongst the listed acute antimigraines. The present study is a continuation of our ongoing programme on structure elucidation of drug molecules.

The molecular structures of (I) and its malate salt, (II), are shown in Figs. 1 and 2, respectively. The bond distances and angles in (I) and (II) (Tables 1 and 3) are similar and agree well with the values found in the related structures sumatriptan (Ravikumar et al., 2006), sumatriptan succinate (Ravikumar et al., 2004), zolmitriptan (Ravikumar et al., 2007a) and rizatriptan benzoate (Ravikumar et al., 2007b).

The conformation of the molecules in both the structures can be defined by the dihedral angle between the mean planes of the indole ring system and the pyrrolidine ring [30.0 (1) in (I) and 27.0 (1)° in (II)]. The ethylamine side chain is in an extended conformation in both the structures. The pyrrolidine ring is in an envelope conformation in (I), whereas it is planar in (II). As seen in other triptan salts, the dimethylammonium atom N2 in (II) also shows quaternary character as a result of proton transfer from the malate anion and consequently bears the positive charge in the molecular cation. The malate anion, in an (-)antiperiplanar conformation, lies perpendicular [with a dihedral angle of 88.9 (1)°] to the indole ring system.

An overlay of the triptans (Fig. 3) superimposing the planar indole ring systems, reveals the significant orientation differences. The solid-state conformation found in the triptans can be characterized in terms of the torsion angles τ1 (C1—C2—C9—C10) and τ2 (C5—C13—S1—N3) (Table 5). Two principal orientations can be noted here for both the side chain substituted at atom C2 {synperiplanar [∓(0–30)°] and anticlinal [∓(90–150)°]} and that at C5 {synclinal [∓(90–150)°] and antiperiplanar [∓(150–180)°]}, indicating the flexibility of the molecule. Structural features were correlated using the theoretical 5-HT_1B-like receptor model (Moloney et al., 1999), on parameters describing the benzene ring and two terminal N atoms (N2 and N3). The distance between the center of the benzene ring and atom N2 is 6.45 Å in (I) and 6.37 Å in (II). The corresponding distances are 6.41 Å in sumatriptan, 5.82 Å in sumatriptan succinate, 5.24 Å in zolmitriptan and 5.71 Å in rizatriptan benzoate. The distance between the center of the benzene ring and atom N3 is 4.14 Å in (I) and 5.31 Å in (II), the corresponding distances in the above-mentioned triptans being 5.34, 5.30, 4.13 and 3.70 Å, respectively.

In (I), N—H···N hydrogen bonds (Table 2) form the primary motif of crystal packing (Fig. 4), resulting in an infinite chain along the b axis. On the other hand, in (II), both the almotriptan cation and the malate anion, each having two potential hydrogen-bond donors, are engaged in O—H···O and N—H···O hydrogen bonds (Table 4). The association of the malate ions forms R₂²(10) and R₄⁴(20) rings (Bernstein et al., 1995) along the c axis (Fig. 5). Further analysis of the crystal packing reveals possible C—H···O and C—H···π interactions in both the structures. Indole ring system stacking [3.665 (2) Å] is seen in (I).

Related literature

For related literature, see: Bernstein et al. (1995); De Vries, Villalón & Saxena (1999); Humphrey et al. (1990); Moloney et al. (1999); Perry & Markham (1998); Ravikumar et al. (2004, 2006, 2007a, 2007b).

S2. Experimental

Crystals of (I) and (II) (SMS Pharma Research Centre, Hyderabad) suitable for X-ray diffraction were obtained from a methanol solution.

S3. Refinement

All N– and O-bound H atoms of both (I) and (II) were located in a difference density map and refined isotropically. In (II), the O4—H4O distance was restrained with a set value of 0.82 (1) Å. A distance restraint was also applied for the C15—C16 bond of the pyrrolidine ring in (II). All other H atoms were positioned geometrically and were treated as riding on their parent C atoms, with C—H distances of 0.93–0.98 Å, and with U_iso(H) values of 1.5U_eq(C) for methyl H and 1.2U_eq(C) for other H atoms. The methyl groups were allowed to rotate but not to tip.

Computing details

For both compounds, data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT (Bruker, 2001); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL/PC (Sheldrick, 1990) and PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997).

Figures

	Fig. 1. A view of (I), with the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. A view of (II), with the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii. the intramolecular hydrogen bond is shown as a dashed line.
	Fig. 3. An overlay of triptans viz. almotriptan, (I) (labelled 1), almotriptan malate, (II) (labelled 2, r.m.s. deviation = 0.013 Å), sumatriptan (labelled 3, r.m.s. deviation = 0.017 Å), sumatriptan succinate (labelled 4, r.m.s. deviation = 0.021 Å), zolmitriptan (labelled 5, r.m.s. deviation = 0.016 Å) and rizatriptan benzoate (labelled 6, r.m.s. deviation = 0.012 Å).
	Fig. 4. Part of the crystal packing for (I), viewed down the a axis, showing the N—H···N hydrogen bonded (dashed lines) chains running along the b axis. H atoms not involved in hydrogen bonding have been omitted for clarity. [Symmetry code: (i) x, y + 1, z.]
	Fig. 5. Part of the crystal packing for (II), showing the N—H···O and O—H···O hydrogen bonded (dashed lines) networks, highlighting the association of malate ions via R2^2(10) and R4^4(20) ring formation along the c axis. H atoms not involved in hydrogen bonding have been omitted for clarity. [Symmetry codes: (i) x - 1, y, z; (ii) x, y + 1, z; (iii) x + 1, y, z and (iv) -x + 1, -y, -z + 2.]

(I) N,N-dimethyl-2-[5-(pyrrolidin-1-ylsulfonylmethyl)-1H- indol-3-yl]-ethanamine

Crystal data

C17H25N3O2S	F(000) = 1440
Mr = 335.46	Dx = 1.280 Mg m^−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2yc	Cell parameters from 1760 reflections
a = 20.5023 (17) Å	θ = 2.4–19.8°
b = 7.6894 (6) Å	µ = 0.20 mm^−1
c = 22.8470 (19) Å	T = 294 K
β = 104.904 (2)°	Block, colorless
V = 3480.7 (5) Å^3	0.22 × 0.16 × 0.09 mm
Z = 8

Data collection

Bruker SMART APEX CCD area-detector diffractometer	2285 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.068
Graphite monochromator	θmax = 25.0°, θmin = 1.8°
ω scan	h = −24→24
16157 measured reflections	k = −9→9
3057 independent reflections	l = −27→27

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.078	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.162	H atoms treated by a mixture of independent and constrained refinement
S = 1.17	w = 1/[σ^2(Fo^2) + (0.0557P)^2 + 4.6989P] where P = (Fo^2 + 2Fc^2)/3
3057 reflections	(Δ/σ)max < 0.001
214 parameters	Δρmax = 0.37 e Å^−3
0 restraints	Δρmin = −0.24 e Å^−3

Special details

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
C1	0.12062 (18)	0.5985 (4)	0.37559 (15)	0.0366 (9)
H1	0.1327	0.5861	0.4175	0.044*
C2	0.10799 (17)	0.4643 (4)	0.33577 (14)	0.0323 (8)
C3	0.09142 (16)	0.5423 (4)	0.27666 (14)	0.0300 (8)
C4	0.07313 (16)	0.4779 (5)	0.21760 (14)	0.0342 (8)
H4	0.0689	0.3585	0.2112	0.041*
C5	0.06124 (17)	0.5886 (5)	0.16879 (14)	0.0354 (8)
C6	0.06594 (18)	0.7693 (5)	0.17914 (16)	0.0433 (9)
H6	0.0575	0.8442	0.1461	0.052*
C7	0.08251 (18)	0.8378 (5)	0.23618 (16)	0.0420 (9)
H7	0.0851	0.9575	0.2421	0.050*
C8	0.09548 (16)	0.7245 (4)	0.28526 (14)	0.0320 (8)
C9	0.1075 (2)	0.2737 (5)	0.34959 (15)	0.0443 (10)
H9A	0.1245	0.2101	0.3200	0.053*
H9B	0.0613	0.2370	0.3455	0.053*
C10	0.1490 (2)	0.2273 (5)	0.41182 (16)	0.0498 (10)
H10A	0.1964	0.2432	0.4135	0.060*
H10B	0.1379	0.3061	0.4410	0.060*
C11	0.0775 (2)	0.0334 (5)	0.45010 (19)	0.0573 (11)
H11A	0.0716	−0.0849	0.4612	0.086*
H11B	0.0392	0.0687	0.4184	0.086*
H11C	0.0813	0.1073	0.4847	0.086*
C12	0.1960 (2)	−0.0103 (6)	0.47694 (18)	0.0612 (12)
H12A	0.2010	0.0638	0.5116	0.092*
H12B	0.2362	−0.0046	0.4627	0.092*
H12C	0.1889	−0.1279	0.4880	0.092*
C13	0.04359 (18)	0.5201 (5)	0.10521 (15)	0.0443 (9)
H13A	0.0126	0.6006	0.0794	0.053*
H13B	0.0203	0.4100	0.1044	0.053*
C14	0.2182 (2)	0.4049 (6)	0.17041 (19)	0.0595 (12)
H14A	0.2044	0.5030	0.1911	0.071*
H14B	0.2592	0.4352	0.1589	0.071*
C15	0.2286 (2)	0.2452 (7)	0.2097 (2)	0.0759 (15)
H15A	0.2008	0.2493	0.2382	0.091*
H15B	0.2755	0.2338	0.2320	0.091*
C16	0.2077 (2)	0.0975 (7)	0.1657 (2)	0.0767 (15)
H16A	0.2433	0.0679	0.1466	0.092*
H16B	0.1961	−0.0048	0.1858	0.092*
C17	0.1470 (2)	0.1683 (5)	0.12026 (19)	0.0596 (12)
H17A	0.1408	0.1121	0.0812	0.072*
H17B	0.1063	0.1540	0.1341	0.072*
N1	0.11326 (16)	0.7545 (4)	0.34578 (13)	0.0399 (8)
H1N	0.1201 (16)	0.845 (4)	0.3638 (15)	0.040 (10)*
N2	0.13825 (16)	0.0472 (4)	0.42904 (12)	0.0401 (8)
N3	0.16437 (16)	0.3539 (4)	0.11721 (13)	0.0487 (8)
O1	0.15023 (16)	0.6501 (4)	0.07875 (14)	0.0703 (9)
O2	0.08893 (16)	0.4082 (4)	0.01711 (11)	0.0717 (10)
S1	0.11450 (5)	0.48884 (14)	0.07475 (4)	0.0467 (3)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.050 (2)	0.037 (2)	0.0233 (18)	−0.0040 (17)	0.0095 (16)	−0.0007 (15)
C2	0.041 (2)	0.0280 (19)	0.0288 (18)	−0.0043 (15)	0.0108 (15)	−0.0008 (14)
C3	0.0312 (19)	0.0306 (19)	0.0308 (18)	−0.0015 (15)	0.0124 (14)	−0.0017 (14)
C4	0.040 (2)	0.033 (2)	0.0310 (19)	−0.0013 (16)	0.0108 (15)	−0.0029 (15)
C5	0.0311 (19)	0.049 (2)	0.0270 (18)	0.0044 (16)	0.0086 (15)	−0.0009 (16)
C6	0.051 (2)	0.046 (2)	0.034 (2)	0.0044 (19)	0.0140 (17)	0.0118 (17)
C7	0.052 (2)	0.032 (2)	0.043 (2)	0.0017 (17)	0.0147 (18)	0.0006 (17)
C8	0.0331 (19)	0.034 (2)	0.0301 (18)	0.0005 (15)	0.0101 (15)	−0.0016 (15)
C9	0.065 (3)	0.037 (2)	0.028 (2)	−0.0057 (19)	0.0073 (18)	−0.0019 (16)
C10	0.068 (3)	0.036 (2)	0.042 (2)	−0.008 (2)	0.008 (2)	−0.0013 (18)
C11	0.072 (3)	0.047 (3)	0.054 (3)	−0.007 (2)	0.018 (2)	0.003 (2)
C12	0.075 (3)	0.055 (3)	0.048 (2)	0.000 (2)	0.006 (2)	0.005 (2)
C13	0.047 (2)	0.054 (2)	0.0297 (19)	0.0052 (19)	0.0047 (16)	0.0039 (17)
C14	0.042 (2)	0.076 (3)	0.057 (3)	0.001 (2)	0.007 (2)	−0.001 (2)
C15	0.045 (3)	0.111 (4)	0.065 (3)	0.007 (3)	0.002 (2)	0.028 (3)
C16	0.067 (3)	0.070 (3)	0.099 (4)	0.024 (3)	0.033 (3)	0.034 (3)
C17	0.075 (3)	0.054 (3)	0.051 (3)	0.004 (2)	0.017 (2)	−0.007 (2)
N1	0.058 (2)	0.0278 (18)	0.0342 (18)	−0.0043 (16)	0.0128 (15)	−0.0068 (14)
N2	0.059 (2)	0.0273 (16)	0.0317 (16)	−0.0032 (14)	0.0068 (15)	0.0010 (12)
N3	0.054 (2)	0.050 (2)	0.0390 (18)	0.0041 (17)	0.0064 (15)	−0.0028 (15)
O1	0.088 (2)	0.058 (2)	0.078 (2)	0.0007 (17)	0.0443 (18)	0.0214 (16)
O2	0.090 (2)	0.101 (2)	0.0239 (14)	0.0247 (19)	0.0136 (14)	−0.0015 (14)
S1	0.0587 (6)	0.0573 (7)	0.0277 (5)	0.0093 (5)	0.0174 (4)	0.0074 (5)

Geometric parameters (Å, º)

C1—C2	1.356 (4)	C11—H11C	0.9600
C1—N1	1.369 (4)	C12—N2	1.459 (5)
C1—H1	0.9300	C12—H12A	0.9600
C2—C3	1.436 (4)	C12—H12B	0.9600
C2—C9	1.499 (5)	C12—H12C	0.9600
C3—C4	1.395 (4)	C13—S1	1.782 (4)
C3—C8	1.415 (4)	C13—H13A	0.9700
C4—C5	1.374 (5)	C13—H13B	0.9700
C4—H4	0.9300	C14—N3	1.470 (5)
C5—C6	1.408 (5)	C14—C15	1.503 (6)
C5—C13	1.499 (4)	C14—H14A	0.9700
C6—C7	1.365 (5)	C14—H14B	0.9700
C6—H6	0.9300	C15—C16	1.504 (7)
C7—C8	1.390 (5)	C15—H15A	0.9700
C7—H7	0.9300	C15—H15B	0.9700
C8—N1	1.356 (4)	C16—C17	1.504 (6)
C9—C10	1.500 (5)	C16—H16A	0.9700
C9—H9A	0.9700	C16—H16B	0.9700
C9—H9B	0.9700	C17—N3	1.477 (5)
C10—N2	1.472 (4)	C17—H17A	0.9700
C10—H10A	0.9700	C17—H17B	0.9700
C10—H10B	0.9700	N1—H1N	0.80 (3)
C11—N2	1.451 (5)	N3—S1	1.598 (3)
C11—H11A	0.9600	O1—S1	1.431 (3)
C11—H11B	0.9600	O2—S1	1.428 (3)
C2—C1—N1	110.8 (3)	H12B—C12—H12C	109.5
C2—C1—H1	124.6	C5—C13—S1	114.1 (2)
N1—C1—H1	124.6	C5—C13—H13A	108.7
C1—C2—C3	105.7 (3)	S1—C13—H13A	108.7
C1—C2—C9	127.8 (3)	C5—C13—H13B	108.7
C3—C2—C9	126.4 (3)	S1—C13—H13B	108.7
C4—C3—C8	118.5 (3)	H13A—C13—H13B	107.6
C4—C3—C2	134.5 (3)	N3—C14—C15	103.7 (4)
C8—C3—C2	107.0 (3)	N3—C14—H14A	111.0
C5—C4—C3	120.8 (3)	C15—C14—H14A	111.0
C5—C4—H4	119.6	N3—C14—H14B	111.0
C3—C4—H4	119.6	C15—C14—H14B	111.0
C4—C5—C6	119.0 (3)	H14A—C14—H14B	109.0
C4—C5—C13	121.1 (3)	C14—C15—C16	104.2 (4)
C6—C5—C13	119.9 (3)	C14—C15—H15A	110.9
C7—C6—C5	122.0 (3)	C16—C15—H15A	110.9
C7—C6—H6	119.0	C14—C15—H15B	110.9
C5—C6—H6	119.0	C16—C15—H15B	110.9
C6—C7—C8	118.5 (3)	H15A—C15—H15B	108.9
C6—C7—H7	120.8	C17—C16—C15	103.4 (4)
C8—C7—H7	120.8	C17—C16—H16A	111.1
N1—C8—C7	131.4 (3)	C15—C16—H16A	111.1
N1—C8—C3	107.5 (3)	C17—C16—H16B	111.1
C7—C8—C3	121.1 (3)	C15—C16—H16B	111.1
C2—C9—C10	113.5 (3)	H16A—C16—H16B	109.1
C2—C9—H9A	108.9	N3—C17—C16	102.4 (4)
C10—C9—H9A	108.9	N3—C17—H17A	111.3
C2—C9—H9B	108.9	C16—C17—H17A	111.3
C10—C9—H9B	108.9	N3—C17—H17B	111.3
H9A—C9—H9B	107.7	C16—C17—H17B	111.3
N2—C10—C9	112.9 (3)	H17A—C17—H17B	109.2
N2—C10—H10A	109.0	C8—N1—C1	108.9 (3)
C9—C10—H10A	109.0	C8—N1—H1N	130 (2)
N2—C10—H10B	109.0	C1—N1—H1N	122 (2)
C9—C10—H10B	109.0	C11—N2—C12	109.3 (3)
H10A—C10—H10B	107.8	C11—N2—C10	111.0 (3)
N2—C11—H11A	109.5	C12—N2—C10	109.7 (3)
N2—C11—H11B	109.5	C14—N3—C17	111.0 (3)
H11A—C11—H11B	109.5	C14—N3—S1	123.8 (3)
N2—C11—H11C	109.5	C17—N3—S1	122.1 (3)
H11A—C11—H11C	109.5	O2—S1—O1	119.74 (19)
H11B—C11—H11C	109.5	O2—S1—N3	107.68 (18)
N2—C12—H12A	109.5	O1—S1—N3	106.67 (19)
N2—C12—H12B	109.5	O2—S1—C13	106.01 (18)
H12A—C12—H12B	109.5	O1—S1—C13	108.28 (19)
N2—C12—H12C	109.5	N3—S1—C13	108.02 (17)
H12A—C12—H12C	109.5
N1—C1—C2—C3	−0.1 (4)	C6—C5—C13—S1	87.7 (4)
N1—C1—C2—C9	−177.1 (3)	N3—C14—C15—C16	27.4 (4)
C1—C2—C3—C4	−179.3 (4)	C14—C15—C16—C17	−39.3 (5)
C9—C2—C3—C4	−2.2 (6)	C15—C16—C17—N3	35.0 (4)
C1—C2—C3—C8	0.1 (4)	C7—C8—N1—C1	−179.6 (4)
C9—C2—C3—C8	177.2 (3)	C3—C8—N1—C1	0.1 (4)
C8—C3—C4—C5	1.9 (5)	C2—C1—N1—C8	0.0 (4)
C2—C3—C4—C5	−178.8 (3)	C9—C10—N2—C11	−81.0 (4)
C3—C4—C5—C6	−1.8 (5)	C9—C10—N2—C12	158.1 (3)
C3—C4—C5—C13	178.1 (3)	C15—C14—N3—C17	−5.4 (4)
C4—C5—C6—C7	0.6 (5)	C15—C14—N3—S1	154.9 (3)
C13—C5—C6—C7	−179.3 (3)	C16—C17—N3—C14	−18.6 (5)
C5—C6—C7—C8	0.4 (5)	C16—C17—N3—S1	−179.3 (3)
C6—C7—C8—N1	179.4 (4)	C14—N3—S1—O2	157.1 (3)
C6—C7—C8—C3	−0.3 (5)	C17—N3—S1—O2	−44.7 (4)
C4—C3—C8—N1	179.4 (3)	C14—N3—S1—O1	27.4 (4)
C2—C3—C8—N1	−0.1 (4)	C17—N3—S1—O1	−174.4 (3)
C4—C3—C8—C7	−0.9 (5)	C14—N3—S1—C13	−88.8 (3)
C2—C3—C8—C7	179.6 (3)	C17—N3—S1—C13	69.4 (3)
C1—C2—C9—C10	−23.7 (6)	C5—C13—S1—O2	174.5 (3)
C3—C2—C9—C10	159.8 (3)	C5—C13—S1—O1	−55.9 (3)
C2—C9—C10—N2	169.3 (3)	C5—C13—S1—N3	59.3 (3)
C4—C5—C13—S1	−92.2 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···N2^i	0.80 (3)	2.12 (3)	2.906 (4)	167 (3)
C15—H15B···Cg2^ii	0.97	2.96	3.909 (5)	166

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

(II) N,N-dimethyl-2-[5-(pyrrolidin-1-ylsulfonylmethyl)-1H- indol-3-yl]-ethanaminium malate

Crystal data

C17H26N3O2S^+·C4H5O5^−	Z = 2
Mr = 469.55	F(000) = 500
Triclinic, P1	Dx = 1.342 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 7.5542 (7) Å	Cell parameters from 8093 reflections
b = 9.3561 (9) Å	θ = 2.3–27.9°
c = 17.3608 (17) Å	µ = 0.19 mm^−1
α = 104.081 (2)°	T = 294 K
β = 101.121 (2)°	Block, colorless
γ = 92.681 (2)°	0.19 × 0.14 × 0.08 mm
V = 1162.13 (19) Å^3

Data collection

Bruker SMART APEX CCD area-detector diffractometer	3743 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.017
Graphite monochromator	θmax = 25.0°, θmin = 2.3°
ω scan	h = −8→8
11188 measured reflections	k = −11→11
4062 independent reflections	l = −20→20

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.049	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.133	H atoms treated by a mixture of independent and constrained refinement
S = 1.03	w = 1/[σ^2(Fo^2) + (0.0713P)^2 + 0.5979P] where P = (Fo^2 + 2Fc^2)/3
4062 reflections	(Δ/σ)max = 0.001
307 parameters	Δρmax = 0.43 e Å^−3
2 restraints	Δρmin = −0.33 e Å^−3

Special details

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
C1	0.3565 (3)	0.5689 (2)	0.81591 (13)	0.0496 (5)
H1	0.4444	0.5665	0.8611	0.059*
C2	0.3736 (3)	0.6561 (2)	0.76450 (12)	0.0421 (4)
C3	0.2072 (3)	0.6248 (2)	0.70411 (11)	0.0387 (4)
C4	0.1382 (3)	0.6780 (2)	0.63659 (11)	0.0392 (4)
H4	0.2083	0.7475	0.6222	0.047*
C5	−0.0348 (3)	0.6265 (2)	0.59154 (12)	0.0425 (4)
C6	−0.1393 (3)	0.5187 (2)	0.61262 (14)	0.0514 (5)
H6	−0.2548	0.4842	0.5814	0.062*
C7	−0.0752 (3)	0.4635 (2)	0.67779 (14)	0.0522 (5)
H7	−0.1452	0.3921	0.6909	0.063*
C8	0.0977 (3)	0.5175 (2)	0.72382 (12)	0.0434 (4)
C9	0.5257 (3)	0.7690 (2)	0.76954 (13)	0.0504 (5)
H9A	0.4934	0.8667	0.7933	0.060*
H9B	0.5410	0.7664	0.7150	0.060*
C10	0.7042 (3)	0.7446 (2)	0.81952 (13)	0.0449 (5)
H10A	0.6826	0.7217	0.8687	0.054*
H10B	0.7526	0.6600	0.7888	0.054*
C11	1.0119 (3)	0.8527 (3)	0.89491 (14)	0.0593 (6)
H11A	1.0923	0.9423	0.9127	0.089*
H11B	1.0693	0.7750	0.8648	0.089*
H11C	0.9839	0.8252	0.9413	0.089*
C12	0.8827 (3)	0.9256 (3)	0.77177 (14)	0.0596 (6)
H12A	0.9356	0.8486	0.7388	0.089*
H12B	0.9662	1.0134	0.7909	0.089*
H12C	0.7726	0.9463	0.7401	0.089*
C13	−0.1144 (3)	0.6828 (2)	0.51917 (12)	0.0476 (5)
H13A	−0.1778	0.6000	0.4756	0.057*
H13B	−0.0168	0.7252	0.5002	0.057*
C14	−0.2510 (4)	0.9455 (3)	0.41993 (16)	0.0735 (8)
H14A	−0.1244	0.9268	0.4288	0.088*
H14B	−0.2590	1.0501	0.4421	0.088*
C15	−0.3352 (6)	0.8996 (5)	0.33358 (19)	0.1132 (15)
H15A	−0.3753	0.9851	0.3152	0.136*
H15B	−0.2473	0.8575	0.3028	0.136*
C16	−0.4875 (5)	0.7917 (4)	0.31961 (18)	0.1004 (12)
H16A	−0.4744	0.7036	0.2789	0.120*
H16B	−0.5987	0.8317	0.3000	0.120*
C17	−0.4956 (4)	0.7541 (3)	0.39624 (16)	0.0737 (8)
H17A	−0.6137	0.7684	0.4094	0.088*
H17B	−0.4719	0.6520	0.3929	0.088*
N1	0.1925 (3)	0.4855 (2)	0.79181 (12)	0.0516 (5)
H1N	0.163 (3)	0.423 (3)	0.8129 (15)	0.053 (7)*
N2	0.8417 (2)	0.8767 (2)	0.84211 (10)	0.0405 (4)
H2N	0.795 (3)	0.948 (2)	0.8705 (13)	0.041 (6)*
N3	−0.3541 (2)	0.8557 (2)	0.45714 (12)	0.0555 (5)
O1	−0.1631 (2)	0.95083 (19)	0.59370 (10)	0.0642 (5)
O2	−0.4126 (2)	0.7547 (2)	0.56822 (11)	0.0696 (5)
S1	−0.26839 (7)	0.81938 (6)	0.54157 (3)	0.04687 (18)
C18	0.8886 (3)	0.3345 (2)	0.91463 (15)	0.0514 (5)
C19	0.7153 (3)	0.3468 (2)	0.94722 (16)	0.0541 (6)
H19A	0.7453	0.3690	1.0061	0.065*
H19B	0.6528	0.4273	0.9320	0.065*
C20	0.5928 (3)	0.2046 (2)	0.91385 (13)	0.0432 (5)
H20	0.5662	0.1827	0.8544	0.052*
C21	0.4134 (2)	0.2173 (2)	0.94254 (13)	0.0432 (5)
O3	0.8941 (2)	0.3315 (3)	0.84577 (13)	0.0913 (7)
O4	1.0288 (2)	0.3294 (2)	0.96938 (13)	0.0739 (6)
H4O	1.125 (3)	0.325 (4)	0.952 (2)	0.109 (12)*
O5	0.6814 (2)	0.08617 (16)	0.93734 (9)	0.0453 (4)
H5O	0.615 (4)	0.048 (3)	0.9593 (17)	0.071 (9)*
O6	0.3180 (2)	0.3113 (2)	0.91909 (13)	0.0735 (6)
O7	0.3758 (2)	0.13715 (18)	0.98469 (10)	0.0578 (4)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0501 (12)	0.0568 (12)	0.0435 (11)	0.0109 (10)	0.0035 (9)	0.0201 (9)
C2	0.0418 (11)	0.0444 (10)	0.0402 (10)	0.0078 (8)	0.0044 (8)	0.0139 (8)
C3	0.0403 (10)	0.0375 (9)	0.0389 (10)	0.0060 (8)	0.0088 (8)	0.0105 (8)
C4	0.0406 (10)	0.0382 (10)	0.0405 (10)	0.0045 (8)	0.0085 (8)	0.0131 (8)
C5	0.0428 (11)	0.0448 (10)	0.0395 (10)	0.0059 (8)	0.0065 (8)	0.0114 (8)
C6	0.0427 (11)	0.0545 (12)	0.0541 (12)	−0.0029 (9)	0.0026 (9)	0.0159 (10)
C7	0.0484 (12)	0.0518 (12)	0.0585 (13)	−0.0054 (9)	0.0093 (10)	0.0217 (10)
C8	0.0478 (11)	0.0420 (10)	0.0436 (10)	0.0062 (8)	0.0112 (9)	0.0154 (8)
C9	0.0437 (11)	0.0571 (12)	0.0493 (12)	0.0018 (9)	−0.0036 (9)	0.0228 (10)
C10	0.0404 (11)	0.0481 (11)	0.0465 (11)	0.0097 (8)	0.0055 (8)	0.0144 (9)
C11	0.0406 (12)	0.0813 (16)	0.0543 (13)	0.0110 (11)	−0.0029 (10)	0.0232 (12)
C12	0.0534 (13)	0.0811 (16)	0.0497 (12)	0.0040 (12)	0.0117 (10)	0.0270 (12)
C13	0.0469 (11)	0.0565 (12)	0.0372 (10)	0.0053 (9)	0.0035 (8)	0.0120 (9)
C14	0.0746 (17)	0.0808 (18)	0.0670 (16)	−0.0221 (14)	−0.0034 (13)	0.0423 (14)
C15	0.144 (3)	0.128 (3)	0.0612 (18)	−0.050 (3)	−0.001 (2)	0.0425 (19)
C16	0.107 (3)	0.123 (3)	0.0554 (16)	−0.031 (2)	−0.0073 (16)	0.0216 (17)
C17	0.0564 (15)	0.0854 (18)	0.0709 (16)	−0.0219 (13)	−0.0197 (12)	0.0357 (14)
N1	0.0564 (11)	0.0545 (11)	0.0518 (10)	0.0046 (9)	0.0113 (9)	0.0290 (9)
N2	0.0356 (8)	0.0507 (10)	0.0356 (8)	0.0126 (7)	0.0069 (7)	0.0110 (7)
N3	0.0452 (10)	0.0657 (12)	0.0551 (11)	−0.0105 (9)	−0.0073 (8)	0.0319 (9)
O1	0.0751 (11)	0.0598 (10)	0.0486 (9)	0.0047 (8)	−0.0006 (8)	0.0078 (7)
O2	0.0517 (10)	0.0985 (13)	0.0783 (12)	0.0144 (9)	0.0225 (9)	0.0519 (11)
S1	0.0419 (3)	0.0587 (3)	0.0429 (3)	0.0057 (2)	0.0046 (2)	0.0217 (2)
C18	0.0346 (11)	0.0562 (12)	0.0762 (15)	0.0063 (9)	0.0202 (10)	0.0339 (11)
C19	0.0338 (11)	0.0524 (12)	0.0860 (16)	0.0100 (9)	0.0227 (10)	0.0273 (11)
C20	0.0325 (10)	0.0523 (11)	0.0514 (11)	0.0080 (8)	0.0124 (8)	0.0225 (9)
C21	0.0269 (9)	0.0500 (11)	0.0585 (12)	0.0043 (8)	0.0108 (8)	0.0234 (10)
O3	0.0446 (10)	0.162 (2)	0.0754 (13)	−0.0019 (11)	0.0155 (9)	0.0458 (14)
O4	0.0395 (9)	0.1181 (16)	0.0935 (13)	0.0297 (9)	0.0307 (9)	0.0651 (12)
O5	0.0420 (8)	0.0471 (8)	0.0596 (9)	0.0152 (6)	0.0258 (7)	0.0238 (7)
O6	0.0376 (8)	0.0943 (13)	0.1247 (16)	0.0289 (8)	0.0363 (9)	0.0770 (12)
O7	0.0429 (8)	0.0722 (10)	0.0796 (11)	0.0185 (7)	0.0276 (8)	0.0457 (9)

Geometric parameters (Å, º)

C1—N1	1.367 (3)	C13—H13B	0.9700
C1—C2	1.367 (3)	C14—N3	1.459 (3)
C1—H1	0.9300	C14—C15	1.459 (4)
C2—C3	1.440 (3)	C14—H14A	0.9700
C2—C9	1.499 (3)	C14—H14B	0.9700
C3—C4	1.402 (3)	C15—C16	1.437 (4)
C3—C8	1.417 (3)	C15—H15A	0.9700
C4—C5	1.383 (3)	C15—H15B	0.9700
C4—H4	0.9300	C16—C17	1.468 (4)
C5—C6	1.411 (3)	C16—H16A	0.9700
C5—C13	1.509 (3)	C16—H16B	0.9700
C6—C7	1.370 (3)	C17—N3	1.464 (3)
C6—H6	0.9300	C17—H17A	0.9700
C7—C8	1.393 (3)	C17—H17B	0.9700
C7—H7	0.9300	N1—H1N	0.81 (2)
C8—N1	1.364 (3)	N2—H2N	0.86 (2)
C9—C10	1.516 (3)	N3—S1	1.6064 (18)
C9—H9A	0.9700	O1—S1	1.4331 (17)
C9—H9B	0.9700	O2—S1	1.4272 (17)
C10—N2	1.499 (3)	C18—O3	1.198 (3)
C10—H10A	0.9700	C18—O4	1.290 (3)
C10—H10B	0.9700	C18—C19	1.522 (3)
C11—N2	1.489 (2)	C19—C20	1.505 (3)
C11—H11A	0.9600	C19—H19A	0.9700
C11—H11B	0.9600	C19—H19B	0.9700
C11—H11C	0.9600	C20—O5	1.424 (2)
C12—N2	1.483 (3)	C20—C21	1.531 (3)
C12—H12A	0.9600	C20—H20	0.9800
C12—H12B	0.9600	C21—O7	1.227 (2)
C12—H12C	0.9600	C21—O6	1.257 (2)
C13—S1	1.791 (2)	O4—H4O	0.833 (10)
C13—H13A	0.9700	O5—H5O	0.80 (3)
N1—C1—C2	110.68 (18)	C15—C14—H14B	110.8
N1—C1—H1	124.7	H14A—C14—H14B	108.9
C2—C1—H1	124.7	C16—C15—C14	110.1 (3)
C1—C2—C3	105.87 (18)	C16—C15—H15A	109.6
C1—C2—C9	129.03 (18)	C14—C15—H15A	109.6
C3—C2—C9	125.02 (17)	C16—C15—H15B	109.6
C4—C3—C8	118.72 (18)	C14—C15—H15B	109.6
C4—C3—C2	134.48 (18)	H15A—C15—H15B	108.2
C8—C3—C2	106.78 (17)	C15—C16—C17	108.8 (2)
C5—C4—C3	119.70 (18)	C15—C16—H16A	109.9
C5—C4—H4	120.2	C17—C16—H16A	109.9
C3—C4—H4	120.2	C15—C16—H16B	109.9
C4—C5—C6	119.97 (18)	C17—C16—H16B	109.9
C4—C5—C13	121.15 (18)	H16A—C16—H16B	108.3
C6—C5—C13	118.88 (18)	N3—C17—C16	104.8 (2)
C7—C6—C5	121.8 (2)	N3—C17—H17A	110.8
C7—C6—H6	119.1	C16—C17—H17A	110.8
C5—C6—H6	119.1	N3—C17—H17B	110.8
C6—C7—C8	118.0 (2)	C16—C17—H17B	110.8
C6—C7—H7	121.0	H17A—C17—H17B	108.9
C8—C7—H7	121.0	C8—N1—C1	108.96 (18)
N1—C8—C7	130.5 (2)	C8—N1—H1N	126.7 (18)
N1—C8—C3	107.71 (18)	C1—N1—H1N	124.2 (18)
C7—C8—C3	121.78 (18)	C12—N2—C11	110.40 (17)
C2—C9—C10	113.23 (17)	C12—N2—C10	114.21 (17)
C2—C9—H9A	108.9	C11—N2—C10	111.52 (17)
C10—C9—H9A	108.9	C12—N2—H2N	107.3 (14)
C2—C9—H9B	108.9	C11—N2—H2N	107.0 (15)
C10—C9—H9B	108.9	C10—N2—H2N	105.9 (15)
H9A—C9—H9B	107.7	C14—N3—C17	111.4 (2)
N2—C10—C9	112.71 (16)	C14—N3—S1	121.76 (16)
N2—C10—H10A	109.1	C17—N3—S1	121.28 (16)
C9—C10—H10A	109.1	O2—S1—O1	119.06 (12)
N2—C10—H10B	109.1	O2—S1—N3	107.34 (10)
C9—C10—H10B	109.1	O1—S1—N3	107.64 (10)
H10A—C10—H10B	107.8	O2—S1—C13	108.35 (11)
N2—C11—H11A	109.5	O1—S1—C13	107.29 (11)
N2—C11—H11B	109.5	N3—S1—C13	106.52 (10)
H11A—C11—H11B	109.5	O3—C18—O4	123.9 (2)
N2—C11—H11C	109.5	O3—C18—C19	123.4 (2)
H11A—C11—H11C	109.5	O4—C18—C19	112.7 (2)
H11B—C11—H11C	109.5	C20—C19—C18	110.68 (19)
N2—C12—H12A	109.5	C20—C19—H19A	109.5
N2—C12—H12B	109.5	C18—C19—H19A	109.5
H12A—C12—H12B	109.5	C20—C19—H19B	109.5
N2—C12—H12C	109.5	C18—C19—H19B	109.5
H12A—C12—H12C	109.5	H19A—C19—H19B	108.1
H12B—C12—H12C	109.5	O5—C20—C19	110.07 (16)
C5—C13—S1	112.92 (14)	O5—C20—C21	109.95 (16)
C5—C13—H13A	109.0	C19—C20—C21	111.50 (17)
S1—C13—H13A	109.0	O5—C20—H20	108.4
C5—C13—H13B	109.0	C19—C20—H20	108.4
S1—C13—H13B	109.0	C21—C20—H20	108.4
H13A—C13—H13B	107.8	O7—C21—O6	126.49 (18)
N3—C14—C15	104.6 (2)	O7—C21—C20	118.75 (17)
N3—C14—H14A	110.8	O6—C21—C20	114.75 (17)
C15—C14—H14A	110.8	C18—O4—H4O	113 (3)
N3—C14—H14B	110.8	C20—O5—H5O	107 (2)
N1—C1—C2—C3	0.2 (2)	C7—C8—N1—C1	−179.0 (2)
N1—C1—C2—C9	177.0 (2)	C3—C8—N1—C1	0.4 (2)
C1—C2—C3—C4	178.6 (2)	C2—C1—N1—C8	−0.4 (3)
C9—C2—C3—C4	1.6 (4)	C9—C10—N2—C12	−57.1 (2)
C1—C2—C3—C8	0.0 (2)	C9—C10—N2—C11	176.86 (18)
C9—C2—C3—C8	−176.91 (19)	C15—C14—N3—C17	1.4 (4)
C8—C3—C4—C5	0.8 (3)	C15—C14—N3—S1	155.3 (3)
C2—C3—C4—C5	−177.6 (2)	C16—C17—N3—C14	−4.5 (4)
C3—C4—C5—C6	−1.3 (3)	C16—C17—N3—S1	−158.6 (2)
C3—C4—C5—C13	179.18 (18)	C14—N3—S1—O2	169.3 (2)
C4—C5—C6—C7	0.8 (3)	C17—N3—S1—O2	−39.3 (3)
C13—C5—C6—C7	−179.7 (2)	C14—N3—S1—O1	40.0 (2)
C5—C6—C7—C8	0.4 (3)	C17—N3—S1—O1	−168.5 (2)
C6—C7—C8—N1	178.3 (2)	C14—N3—S1—C13	−74.8 (2)
C6—C7—C8—C3	−0.9 (3)	C17—N3—S1—C13	76.6 (2)
C4—C3—C8—N1	−179.05 (17)	C5—C13—S1—O2	−59.60 (18)
C2—C3—C8—N1	−0.2 (2)	C5—C13—S1—O1	70.15 (18)
C4—C3—C8—C7	0.3 (3)	C5—C13—S1—N3	−174.81 (15)
C2—C3—C8—C7	179.17 (19)	O3—C18—C19—C20	71.6 (3)
C1—C2—C9—C10	22.9 (3)	O4—C18—C19—C20	−109.1 (2)
C3—C2—C9—C10	−160.94 (19)	C18—C19—C20—O5	60.5 (2)
C2—C9—C10—N2	−165.28 (17)	C18—C19—C20—C21	−177.14 (17)
C4—C5—C13—S1	−100.7 (2)	O5—C20—C21—O7	5.1 (3)
C6—C5—C13—S1	79.8 (2)	C19—C20—C21—O7	−117.3 (2)
N3—C14—C15—C16	2.5 (5)	O5—C20—C21—O6	−174.6 (2)
C14—C15—C16—C17	−5.4 (5)	C19—C20—C21—O6	63.0 (3)
C15—C16—C17—N3	5.9 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···O3^i	0.81 (2)	2.39 (3)	3.034 (3)	138 (2)
N1—H1N···O6	0.81 (2)	2.47 (2)	3.087 (2)	135 (2)
N2—H2N···O5^ii	0.86 (2)	1.88 (2)	2.731 (2)	173 (2)
O4—H4O···O6^iii	0.83 (1)	1.67 (1)	2.503 (2)	178 (4)
O5—H5O···O7	0.80 (3)	2.11 (3)	2.623 (2)	122 (3)
O5—H5O···O7^iv	0.80 (3)	2.19 (3)	2.811 (2)	135 (3)
C11—H11C···O4^v	0.96	2.38	3.276 (3)	156
C14—H14A···O1^vi	0.97	2.55	3.301 (3)	134
C11—H11B···Cg1^iii	0.96	2.87	3.819 (3)	172
C12—H12A···Cg2^iii	0.96	2.83	3.767 (3)	164
C13—H13A···Cg2^vii	0.97	2.91	3.577 (1)	127

Symmetry codes: (i) x−1, y, z; (ii) x, y+1, z; (iii) x+1, y, z; (iv) −x+1, −y, −z+2; (v) −x+2, −y+1, −z+2; (vi) −x, −y+2, −z+1; (vii) −x, −y+1, −z+1.