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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.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270107060507/dn3071sup1.cif
Contains datablocks I, II, global

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270107060507/dn3071Isup2.hkl
Contains datablock I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270107060507/dn3071IIsup3.hkl
Contains datablock II

CCDC references: 677217; 677218

Comment top

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-HT1B/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-HT1B/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-HT1B-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 top

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).

Experimental top

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

Refinement top

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 Uiso(H) values of 1.5Ueq(C) for methyl H and 1.2Ueq(C) for other H atoms. The methyl groups were allowed to rotate but not to tip.

Computing details top

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 top
[Figure 1] 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.
[Figure 2] 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.
[Figure 3] 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).
[Figure 4] 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.]
[Figure 5] 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 R22(10) and R44(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 top
Crystal data top
C17H25N3O2SF(000) = 1440
Mr = 335.46Dx = 1.280 Mg m3
Monoclinic, C2/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2ycCell parameters from 1760 reflections
a = 20.5023 (17) Åθ = 2.4–19.8°
b = 7.6894 (6) ŵ = 0.20 mm1
c = 22.8470 (19) ÅT = 294 K
β = 104.904 (2)°Block, colorless
V = 3480.7 (5) Å30.22 × 0.16 × 0.09 mm
Z = 8
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
2285 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.068
Graphite monochromatorθmax = 25.0°, θmin = 1.8°
ω scanh = 2424
16157 measured reflectionsk = 99
3057 independent reflectionsl = 2727
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.078Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.162H atoms treated by a mixture of independent and constrained refinement
S = 1.17 w = 1/[σ2(Fo2) + (0.0557P)2 + 4.6989P]
where P = (Fo2 + 2Fc2)/3
3057 reflections(Δ/σ)max < 0.001
214 parametersΔρmax = 0.37 e Å3
0 restraintsΔρmin = 0.24 e Å3
Crystal data top
C17H25N3O2SV = 3480.7 (5) Å3
Mr = 335.46Z = 8
Monoclinic, C2/cMo Kα radiation
a = 20.5023 (17) ŵ = 0.20 mm1
b = 7.6894 (6) ÅT = 294 K
c = 22.8470 (19) Å0.22 × 0.16 × 0.09 mm
β = 104.904 (2)°
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
2285 reflections with I > 2σ(I)
16157 measured reflectionsRint = 0.068
3057 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0780 restraints
wR(F2) = 0.162H atoms treated by a mixture of independent and constrained refinement
S = 1.17Δρmax = 0.37 e Å3
3057 reflectionsΔρmin = 0.24 e Å3
214 parameters
Special details top

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 (Å2) top
xyzUiso*/Ueq
C10.12062 (18)0.5985 (4)0.37559 (15)0.0366 (9)
H10.13270.58610.41750.044*
C20.10799 (17)0.4643 (4)0.33577 (14)0.0323 (8)
C30.09142 (16)0.5423 (4)0.27666 (14)0.0300 (8)
C40.07313 (16)0.4779 (5)0.21760 (14)0.0342 (8)
H40.06890.35850.21120.041*
C50.06124 (17)0.5886 (5)0.16879 (14)0.0354 (8)
C60.06594 (18)0.7693 (5)0.17914 (16)0.0433 (9)
H60.05750.84420.14610.052*
C70.08251 (18)0.8378 (5)0.23618 (16)0.0420 (9)
H70.08510.95750.24210.050*
C80.09548 (16)0.7245 (4)0.28526 (14)0.0320 (8)
C90.1075 (2)0.2737 (5)0.34959 (15)0.0443 (10)
H9A0.12450.21010.32000.053*
H9B0.06130.23700.34550.053*
C100.1490 (2)0.2273 (5)0.41182 (16)0.0498 (10)
H10A0.19640.24320.41350.060*
H10B0.13790.30610.44100.060*
C110.0775 (2)0.0334 (5)0.45010 (19)0.0573 (11)
H11A0.07160.08490.46120.086*
H11B0.03920.06870.41840.086*
H11C0.08130.10730.48470.086*
C120.1960 (2)0.0103 (6)0.47694 (18)0.0612 (12)
H12A0.20100.06380.51160.092*
H12B0.23620.00460.46270.092*
H12C0.18890.12790.48800.092*
C130.04359 (18)0.5201 (5)0.10521 (15)0.0443 (9)
H13A0.01260.60060.07940.053*
H13B0.02030.41000.10440.053*
C140.2182 (2)0.4049 (6)0.17041 (19)0.0595 (12)
H14A0.20440.50300.19110.071*
H14B0.25920.43520.15890.071*
C150.2286 (2)0.2452 (7)0.2097 (2)0.0759 (15)
H15A0.20080.24930.23820.091*
H15B0.27550.23380.23200.091*
C160.2077 (2)0.0975 (7)0.1657 (2)0.0767 (15)
H16A0.24330.06790.14660.092*
H16B0.19610.00480.18580.092*
C170.1470 (2)0.1683 (5)0.12026 (19)0.0596 (12)
H17A0.14080.11210.08120.072*
H17B0.10630.15400.13410.072*
N10.11326 (16)0.7545 (4)0.34578 (13)0.0399 (8)
H1N0.1201 (16)0.845 (4)0.3638 (15)0.040 (10)*
N20.13825 (16)0.0472 (4)0.42904 (12)0.0401 (8)
N30.16437 (16)0.3539 (4)0.11721 (13)0.0487 (8)
O10.15023 (16)0.6501 (4)0.07875 (14)0.0703 (9)
O20.08893 (16)0.4082 (4)0.01711 (11)0.0717 (10)
S10.11450 (5)0.48884 (14)0.07475 (4)0.0467 (3)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.050 (2)0.037 (2)0.0233 (18)0.0040 (17)0.0095 (16)0.0007 (15)
C20.041 (2)0.0280 (19)0.0288 (18)0.0043 (15)0.0108 (15)0.0008 (14)
C30.0312 (19)0.0306 (19)0.0308 (18)0.0015 (15)0.0124 (14)0.0017 (14)
C40.040 (2)0.033 (2)0.0310 (19)0.0013 (16)0.0108 (15)0.0029 (15)
C50.0311 (19)0.049 (2)0.0270 (18)0.0044 (16)0.0086 (15)0.0009 (16)
C60.051 (2)0.046 (2)0.034 (2)0.0044 (19)0.0140 (17)0.0118 (17)
C70.052 (2)0.032 (2)0.043 (2)0.0017 (17)0.0147 (18)0.0006 (17)
C80.0331 (19)0.034 (2)0.0301 (18)0.0005 (15)0.0101 (15)0.0016 (15)
C90.065 (3)0.037 (2)0.028 (2)0.0057 (19)0.0073 (18)0.0019 (16)
C100.068 (3)0.036 (2)0.042 (2)0.008 (2)0.008 (2)0.0013 (18)
C110.072 (3)0.047 (3)0.054 (3)0.007 (2)0.018 (2)0.003 (2)
C120.075 (3)0.055 (3)0.048 (2)0.000 (2)0.006 (2)0.005 (2)
C130.047 (2)0.054 (2)0.0297 (19)0.0052 (19)0.0047 (16)0.0039 (17)
C140.042 (2)0.076 (3)0.057 (3)0.001 (2)0.007 (2)0.001 (2)
C150.045 (3)0.111 (4)0.065 (3)0.007 (3)0.002 (2)0.028 (3)
C160.067 (3)0.070 (3)0.099 (4)0.024 (3)0.033 (3)0.034 (3)
C170.075 (3)0.054 (3)0.051 (3)0.004 (2)0.017 (2)0.007 (2)
N10.058 (2)0.0278 (18)0.0342 (18)0.0043 (16)0.0128 (15)0.0068 (14)
N20.059 (2)0.0273 (16)0.0317 (16)0.0032 (14)0.0068 (15)0.0010 (12)
N30.054 (2)0.050 (2)0.0390 (18)0.0041 (17)0.0064 (15)0.0028 (15)
O10.088 (2)0.058 (2)0.078 (2)0.0007 (17)0.0443 (18)0.0214 (16)
O20.090 (2)0.101 (2)0.0239 (14)0.0247 (19)0.0136 (14)0.0015 (14)
S10.0587 (6)0.0573 (7)0.0277 (5)0.0093 (5)0.0174 (4)0.0074 (5)
Geometric parameters (Å, º) top
C1—C21.356 (4)C11—H11C0.9600
C1—N11.369 (4)C12—N21.459 (5)
C1—H10.9300C12—H12A0.9600
C2—C31.436 (4)C12—H12B0.9600
C2—C91.499 (5)C12—H12C0.9600
C3—C41.395 (4)C13—S11.782 (4)
C3—C81.415 (4)C13—H13A0.9700
C4—C51.374 (5)C13—H13B0.9700
C4—H40.9300C14—N31.470 (5)
C5—C61.408 (5)C14—C151.503 (6)
C5—C131.499 (4)C14—H14A0.9700
C6—C71.365 (5)C14—H14B0.9700
C6—H60.9300C15—C161.504 (7)
C7—C81.390 (5)C15—H15A0.9700
C7—H70.9300C15—H15B0.9700
C8—N11.356 (4)C16—C171.504 (6)
C9—C101.500 (5)C16—H16A0.9700
C9—H9A0.9700C16—H16B0.9700
C9—H9B0.9700C17—N31.477 (5)
C10—N21.472 (4)C17—H17A0.9700
C10—H10A0.9700C17—H17B0.9700
C10—H10B0.9700N1—H1N0.80 (3)
C11—N21.451 (5)N3—S11.598 (3)
C11—H11A0.9600O1—S11.431 (3)
C11—H11B0.9600O2—S11.428 (3)
C2—C1—N1110.8 (3)H12B—C12—H12C109.5
C2—C1—H1124.6C5—C13—S1114.1 (2)
N1—C1—H1124.6C5—C13—H13A108.7
C1—C2—C3105.7 (3)S1—C13—H13A108.7
C1—C2—C9127.8 (3)C5—C13—H13B108.7
C3—C2—C9126.4 (3)S1—C13—H13B108.7
C4—C3—C8118.5 (3)H13A—C13—H13B107.6
C4—C3—C2134.5 (3)N3—C14—C15103.7 (4)
C8—C3—C2107.0 (3)N3—C14—H14A111.0
C5—C4—C3120.8 (3)C15—C14—H14A111.0
C5—C4—H4119.6N3—C14—H14B111.0
C3—C4—H4119.6C15—C14—H14B111.0
C4—C5—C6119.0 (3)H14A—C14—H14B109.0
C4—C5—C13121.1 (3)C14—C15—C16104.2 (4)
C6—C5—C13119.9 (3)C14—C15—H15A110.9
C7—C6—C5122.0 (3)C16—C15—H15A110.9
C7—C6—H6119.0C14—C15—H15B110.9
C5—C6—H6119.0C16—C15—H15B110.9
C6—C7—C8118.5 (3)H15A—C15—H15B108.9
C6—C7—H7120.8C17—C16—C15103.4 (4)
C8—C7—H7120.8C17—C16—H16A111.1
N1—C8—C7131.4 (3)C15—C16—H16A111.1
N1—C8—C3107.5 (3)C17—C16—H16B111.1
C7—C8—C3121.1 (3)C15—C16—H16B111.1
C2—C9—C10113.5 (3)H16A—C16—H16B109.1
C2—C9—H9A108.9N3—C17—C16102.4 (4)
C10—C9—H9A108.9N3—C17—H17A111.3
C2—C9—H9B108.9C16—C17—H17A111.3
C10—C9—H9B108.9N3—C17—H17B111.3
H9A—C9—H9B107.7C16—C17—H17B111.3
N2—C10—C9112.9 (3)H17A—C17—H17B109.2
N2—C10—H10A109.0C8—N1—C1108.9 (3)
C9—C10—H10A109.0C8—N1—H1N130 (2)
N2—C10—H10B109.0C1—N1—H1N122 (2)
C9—C10—H10B109.0C11—N2—C12109.3 (3)
H10A—C10—H10B107.8C11—N2—C10111.0 (3)
N2—C11—H11A109.5C12—N2—C10109.7 (3)
N2—C11—H11B109.5C14—N3—C17111.0 (3)
H11A—C11—H11B109.5C14—N3—S1123.8 (3)
N2—C11—H11C109.5C17—N3—S1122.1 (3)
H11A—C11—H11C109.5O2—S1—O1119.74 (19)
H11B—C11—H11C109.5O2—S1—N3107.68 (18)
N2—C12—H12A109.5O1—S1—N3106.67 (19)
N2—C12—H12B109.5O2—S1—C13106.01 (18)
H12A—C12—H12B109.5O1—S1—C13108.28 (19)
N2—C12—H12C109.5N3—S1—C13108.02 (17)
H12A—C12—H12C109.5
N1—C1—C2—C30.1 (4)C6—C5—C13—S187.7 (4)
N1—C1—C2—C9177.1 (3)N3—C14—C15—C1627.4 (4)
C1—C2—C3—C4179.3 (4)C14—C15—C16—C1739.3 (5)
C9—C2—C3—C42.2 (6)C15—C16—C17—N335.0 (4)
C1—C2—C3—C80.1 (4)C7—C8—N1—C1179.6 (4)
C9—C2—C3—C8177.2 (3)C3—C8—N1—C10.1 (4)
C8—C3—C4—C51.9 (5)C2—C1—N1—C80.0 (4)
C2—C3—C4—C5178.8 (3)C9—C10—N2—C1181.0 (4)
C3—C4—C5—C61.8 (5)C9—C10—N2—C12158.1 (3)
C3—C4—C5—C13178.1 (3)C15—C14—N3—C175.4 (4)
C4—C5—C6—C70.6 (5)C15—C14—N3—S1154.9 (3)
C13—C5—C6—C7179.3 (3)C16—C17—N3—C1418.6 (5)
C5—C6—C7—C80.4 (5)C16—C17—N3—S1179.3 (3)
C6—C7—C8—N1179.4 (4)C14—N3—S1—O2157.1 (3)
C6—C7—C8—C30.3 (5)C17—N3—S1—O244.7 (4)
C4—C3—C8—N1179.4 (3)C14—N3—S1—O127.4 (4)
C2—C3—C8—N10.1 (4)C17—N3—S1—O1174.4 (3)
C4—C3—C8—C70.9 (5)C14—N3—S1—C1388.8 (3)
C2—C3—C8—C7179.6 (3)C17—N3—S1—C1369.4 (3)
C1—C2—C9—C1023.7 (6)C5—C13—S1—O2174.5 (3)
C3—C2—C9—C10159.8 (3)C5—C13—S1—O155.9 (3)
C2—C9—C10—N2169.3 (3)C5—C13—S1—N359.3 (3)
C4—C5—C13—S192.2 (4)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1N···N2i0.80 (3)2.12 (3)2.906 (4)167 (3)
C15—H15B···Cg2ii0.972.963.909 (5)166
Symmetry codes: (i) x, y+1, z; (ii) x, y1, z1/2.
(II) N,N-dimethyl-2-[5-(pyrrolidin-1-ylsulfonylmethyl)-1H- indol-3-yl]-ethanaminium malate top
Crystal data top
C17H26N3O2S+·C4H5O5Z = 2
Mr = 469.55F(000) = 500
Triclinic, P1Dx = 1.342 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 7.5542 (7) ÅCell parameters from 8093 reflections
b = 9.3561 (9) Åθ = 2.3–27.9°
c = 17.3608 (17) ŵ = 0.19 mm1
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) Å3
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
3743 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.017
Graphite monochromatorθmax = 25.0°, θmin = 2.3°
ω scanh = 88
11188 measured reflectionsk = 1111
4062 independent reflectionsl = 2020
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.049Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.133H atoms treated by a mixture of independent and constrained refinement
S = 1.03 w = 1/[σ2(Fo2) + (0.0713P)2 + 0.5979P]
where P = (Fo2 + 2Fc2)/3
4062 reflections(Δ/σ)max = 0.001
307 parametersΔρmax = 0.43 e Å3
2 restraintsΔρmin = 0.33 e Å3
Crystal data top
C17H26N3O2S+·C4H5O5γ = 92.681 (2)°
Mr = 469.55V = 1162.13 (19) Å3
Triclinic, P1Z = 2
a = 7.5542 (7) ÅMo Kα radiation
b = 9.3561 (9) ŵ = 0.19 mm1
c = 17.3608 (17) ÅT = 294 K
α = 104.081 (2)°0.19 × 0.14 × 0.08 mm
β = 101.121 (2)°
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
3743 reflections with I > 2σ(I)
11188 measured reflectionsRint = 0.017
4062 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0492 restraints
wR(F2) = 0.133H atoms treated by a mixture of independent and constrained refinement
S = 1.03Δρmax = 0.43 e Å3
4062 reflectionsΔρmin = 0.33 e Å3
307 parameters
Special details top

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 (Å2) top
xyzUiso*/Ueq
C10.3565 (3)0.5689 (2)0.81591 (13)0.0496 (5)
H10.44440.56650.86110.059*
C20.3736 (3)0.6561 (2)0.76450 (12)0.0421 (4)
C30.2072 (3)0.6248 (2)0.70411 (11)0.0387 (4)
C40.1382 (3)0.6780 (2)0.63659 (11)0.0392 (4)
H40.20830.74750.62220.047*
C50.0348 (3)0.6265 (2)0.59154 (12)0.0425 (4)
C60.1393 (3)0.5187 (2)0.61262 (14)0.0514 (5)
H60.25480.48420.58140.062*
C70.0752 (3)0.4635 (2)0.67779 (14)0.0522 (5)
H70.14520.39210.69090.063*
C80.0977 (3)0.5175 (2)0.72382 (12)0.0434 (4)
C90.5257 (3)0.7690 (2)0.76954 (13)0.0504 (5)
H9A0.49340.86670.79330.060*
H9B0.54100.76640.71500.060*
C100.7042 (3)0.7446 (2)0.81952 (13)0.0449 (5)
H10A0.68260.72170.86870.054*
H10B0.75260.66000.78880.054*
C111.0119 (3)0.8527 (3)0.89491 (14)0.0593 (6)
H11A1.09230.94230.91270.089*
H11B1.06930.77500.86480.089*
H11C0.98390.82520.94130.089*
C120.8827 (3)0.9256 (3)0.77177 (14)0.0596 (6)
H12A0.93560.84860.73880.089*
H12B0.96621.01340.79090.089*
H12C0.77260.94630.74010.089*
C130.1144 (3)0.6828 (2)0.51917 (12)0.0476 (5)
H13A0.17780.60000.47560.057*
H13B0.01680.72520.50020.057*
C140.2510 (4)0.9455 (3)0.41993 (16)0.0735 (8)
H14A0.12440.92680.42880.088*
H14B0.25901.05010.44210.088*
C150.3352 (6)0.8996 (5)0.33358 (19)0.1132 (15)
H15A0.37530.98510.31520.136*
H15B0.24730.85750.30280.136*
C160.4875 (5)0.7917 (4)0.31961 (18)0.1004 (12)
H16A0.47440.70360.27890.120*
H16B0.59870.83170.30000.120*
C170.4956 (4)0.7541 (3)0.39624 (16)0.0737 (8)
H17A0.61370.76840.40940.088*
H17B0.47190.65200.39290.088*
N10.1925 (3)0.4855 (2)0.79181 (12)0.0516 (5)
H1N0.163 (3)0.423 (3)0.8129 (15)0.053 (7)*
N20.8417 (2)0.8767 (2)0.84211 (10)0.0405 (4)
H2N0.795 (3)0.948 (2)0.8705 (13)0.041 (6)*
N30.3541 (2)0.8557 (2)0.45714 (12)0.0555 (5)
O10.1631 (2)0.95083 (19)0.59370 (10)0.0642 (5)
O20.4126 (2)0.7547 (2)0.56822 (11)0.0696 (5)
S10.26839 (7)0.81938 (6)0.54157 (3)0.04687 (18)
C180.8886 (3)0.3345 (2)0.91463 (15)0.0514 (5)
C190.7153 (3)0.3468 (2)0.94722 (16)0.0541 (6)
H19A0.74530.36901.00610.065*
H19B0.65280.42730.93200.065*
C200.5928 (3)0.2046 (2)0.91385 (13)0.0432 (5)
H200.56620.18270.85440.052*
C210.4134 (2)0.2173 (2)0.94254 (13)0.0432 (5)
O30.8941 (2)0.3315 (3)0.84577 (13)0.0913 (7)
O41.0288 (2)0.3294 (2)0.96938 (13)0.0739 (6)
H4O1.125 (3)0.325 (4)0.952 (2)0.109 (12)*
O50.6814 (2)0.08617 (16)0.93734 (9)0.0453 (4)
H5O0.615 (4)0.048 (3)0.9593 (17)0.071 (9)*
O60.3180 (2)0.3113 (2)0.91909 (13)0.0735 (6)
O70.3758 (2)0.13715 (18)0.98469 (10)0.0578 (4)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0501 (12)0.0568 (12)0.0435 (11)0.0109 (10)0.0035 (9)0.0201 (9)
C20.0418 (11)0.0444 (10)0.0402 (10)0.0078 (8)0.0044 (8)0.0139 (8)
C30.0403 (10)0.0375 (9)0.0389 (10)0.0060 (8)0.0088 (8)0.0105 (8)
C40.0406 (10)0.0382 (10)0.0405 (10)0.0045 (8)0.0085 (8)0.0131 (8)
C50.0428 (11)0.0448 (10)0.0395 (10)0.0059 (8)0.0065 (8)0.0114 (8)
C60.0427 (11)0.0545 (12)0.0541 (12)0.0029 (9)0.0026 (9)0.0159 (10)
C70.0484 (12)0.0518 (12)0.0585 (13)0.0054 (9)0.0093 (10)0.0217 (10)
C80.0478 (11)0.0420 (10)0.0436 (10)0.0062 (8)0.0112 (9)0.0154 (8)
C90.0437 (11)0.0571 (12)0.0493 (12)0.0018 (9)0.0036 (9)0.0228 (10)
C100.0404 (11)0.0481 (11)0.0465 (11)0.0097 (8)0.0055 (8)0.0144 (9)
C110.0406 (12)0.0813 (16)0.0543 (13)0.0110 (11)0.0029 (10)0.0232 (12)
C120.0534 (13)0.0811 (16)0.0497 (12)0.0040 (12)0.0117 (10)0.0270 (12)
C130.0469 (11)0.0565 (12)0.0372 (10)0.0053 (9)0.0035 (8)0.0120 (9)
C140.0746 (17)0.0808 (18)0.0670 (16)0.0221 (14)0.0034 (13)0.0423 (14)
C150.144 (3)0.128 (3)0.0612 (18)0.050 (3)0.001 (2)0.0425 (19)
C160.107 (3)0.123 (3)0.0554 (16)0.031 (2)0.0073 (16)0.0216 (17)
C170.0564 (15)0.0854 (18)0.0709 (16)0.0219 (13)0.0197 (12)0.0357 (14)
N10.0564 (11)0.0545 (11)0.0518 (10)0.0046 (9)0.0113 (9)0.0290 (9)
N20.0356 (8)0.0507 (10)0.0356 (8)0.0126 (7)0.0069 (7)0.0110 (7)
N30.0452 (10)0.0657 (12)0.0551 (11)0.0105 (9)0.0073 (8)0.0319 (9)
O10.0751 (11)0.0598 (10)0.0486 (9)0.0047 (8)0.0006 (8)0.0078 (7)
O20.0517 (10)0.0985 (13)0.0783 (12)0.0144 (9)0.0225 (9)0.0519 (11)
S10.0419 (3)0.0587 (3)0.0429 (3)0.0057 (2)0.0046 (2)0.0217 (2)
C180.0346 (11)0.0562 (12)0.0762 (15)0.0063 (9)0.0202 (10)0.0339 (11)
C190.0338 (11)0.0524 (12)0.0860 (16)0.0100 (9)0.0227 (10)0.0273 (11)
C200.0325 (10)0.0523 (11)0.0514 (11)0.0080 (8)0.0124 (8)0.0225 (9)
C210.0269 (9)0.0500 (11)0.0585 (12)0.0043 (8)0.0108 (8)0.0234 (10)
O30.0446 (10)0.162 (2)0.0754 (13)0.0019 (11)0.0155 (9)0.0458 (14)
O40.0395 (9)0.1181 (16)0.0935 (13)0.0297 (9)0.0307 (9)0.0651 (12)
O50.0420 (8)0.0471 (8)0.0596 (9)0.0152 (6)0.0258 (7)0.0238 (7)
O60.0376 (8)0.0943 (13)0.1247 (16)0.0289 (8)0.0363 (9)0.0770 (12)
O70.0429 (8)0.0722 (10)0.0796 (11)0.0185 (7)0.0276 (8)0.0457 (9)
Geometric parameters (Å, º) top
C1—N11.367 (3)C13—H13B0.9700
C1—C21.367 (3)C14—N31.459 (3)
C1—H10.9300C14—C151.459 (4)
C2—C31.440 (3)C14—H14A0.9700
C2—C91.499 (3)C14—H14B0.9700
C3—C41.402 (3)C15—C161.437 (4)
C3—C81.417 (3)C15—H15A0.9700
C4—C51.383 (3)C15—H15B0.9700
C4—H40.9300C16—C171.468 (4)
C5—C61.411 (3)C16—H16A0.9700
C5—C131.509 (3)C16—H16B0.9700
C6—C71.370 (3)C17—N31.464 (3)
C6—H60.9300C17—H17A0.9700
C7—C81.393 (3)C17—H17B0.9700
C7—H70.9300N1—H1N0.81 (2)
C8—N11.364 (3)N2—H2N0.86 (2)
C9—C101.516 (3)N3—S11.6064 (18)
C9—H9A0.9700O1—S11.4331 (17)
C9—H9B0.9700O2—S11.4272 (17)
C10—N21.499 (3)C18—O31.198 (3)
C10—H10A0.9700C18—O41.290 (3)
C10—H10B0.9700C18—C191.522 (3)
C11—N21.489 (2)C19—C201.505 (3)
C11—H11A0.9600C19—H19A0.9700
C11—H11B0.9600C19—H19B0.9700
C11—H11C0.9600C20—O51.424 (2)
C12—N21.483 (3)C20—C211.531 (3)
C12—H12A0.9600C20—H200.9800
C12—H12B0.9600C21—O71.227 (2)
C12—H12C0.9600C21—O61.257 (2)
C13—S11.791 (2)O4—H4O0.833 (10)
C13—H13A0.9700O5—H5O0.80 (3)
N1—C1—C2110.68 (18)C15—C14—H14B110.8
N1—C1—H1124.7H14A—C14—H14B108.9
C2—C1—H1124.7C16—C15—C14110.1 (3)
C1—C2—C3105.87 (18)C16—C15—H15A109.6
C1—C2—C9129.03 (18)C14—C15—H15A109.6
C3—C2—C9125.02 (17)C16—C15—H15B109.6
C4—C3—C8118.72 (18)C14—C15—H15B109.6
C4—C3—C2134.48 (18)H15A—C15—H15B108.2
C8—C3—C2106.78 (17)C15—C16—C17108.8 (2)
C5—C4—C3119.70 (18)C15—C16—H16A109.9
C5—C4—H4120.2C17—C16—H16A109.9
C3—C4—H4120.2C15—C16—H16B109.9
C4—C5—C6119.97 (18)C17—C16—H16B109.9
C4—C5—C13121.15 (18)H16A—C16—H16B108.3
C6—C5—C13118.88 (18)N3—C17—C16104.8 (2)
C7—C6—C5121.8 (2)N3—C17—H17A110.8
C7—C6—H6119.1C16—C17—H17A110.8
C5—C6—H6119.1N3—C17—H17B110.8
C6—C7—C8118.0 (2)C16—C17—H17B110.8
C6—C7—H7121.0H17A—C17—H17B108.9
C8—C7—H7121.0C8—N1—C1108.96 (18)
N1—C8—C7130.5 (2)C8—N1—H1N126.7 (18)
N1—C8—C3107.71 (18)C1—N1—H1N124.2 (18)
C7—C8—C3121.78 (18)C12—N2—C11110.40 (17)
C2—C9—C10113.23 (17)C12—N2—C10114.21 (17)
C2—C9—H9A108.9C11—N2—C10111.52 (17)
C10—C9—H9A108.9C12—N2—H2N107.3 (14)
C2—C9—H9B108.9C11—N2—H2N107.0 (15)
C10—C9—H9B108.9C10—N2—H2N105.9 (15)
H9A—C9—H9B107.7C14—N3—C17111.4 (2)
N2—C10—C9112.71 (16)C14—N3—S1121.76 (16)
N2—C10—H10A109.1C17—N3—S1121.28 (16)
C9—C10—H10A109.1O2—S1—O1119.06 (12)
N2—C10—H10B109.1O2—S1—N3107.34 (10)
C9—C10—H10B109.1O1—S1—N3107.64 (10)
H10A—C10—H10B107.8O2—S1—C13108.35 (11)
N2—C11—H11A109.5O1—S1—C13107.29 (11)
N2—C11—H11B109.5N3—S1—C13106.52 (10)
H11A—C11—H11B109.5O3—C18—O4123.9 (2)
N2—C11—H11C109.5O3—C18—C19123.4 (2)
H11A—C11—H11C109.5O4—C18—C19112.7 (2)
H11B—C11—H11C109.5C20—C19—C18110.68 (19)
N2—C12—H12A109.5C20—C19—H19A109.5
N2—C12—H12B109.5C18—C19—H19A109.5
H12A—C12—H12B109.5C20—C19—H19B109.5
N2—C12—H12C109.5C18—C19—H19B109.5
H12A—C12—H12C109.5H19A—C19—H19B108.1
H12B—C12—H12C109.5O5—C20—C19110.07 (16)
C5—C13—S1112.92 (14)O5—C20—C21109.95 (16)
C5—C13—H13A109.0C19—C20—C21111.50 (17)
S1—C13—H13A109.0O5—C20—H20108.4
C5—C13—H13B109.0C19—C20—H20108.4
S1—C13—H13B109.0C21—C20—H20108.4
H13A—C13—H13B107.8O7—C21—O6126.49 (18)
N3—C14—C15104.6 (2)O7—C21—C20118.75 (17)
N3—C14—H14A110.8O6—C21—C20114.75 (17)
C15—C14—H14A110.8C18—O4—H4O113 (3)
N3—C14—H14B110.8C20—O5—H5O107 (2)
N1—C1—C2—C30.2 (2)C7—C8—N1—C1179.0 (2)
N1—C1—C2—C9177.0 (2)C3—C8—N1—C10.4 (2)
C1—C2—C3—C4178.6 (2)C2—C1—N1—C80.4 (3)
C9—C2—C3—C41.6 (4)C9—C10—N2—C1257.1 (2)
C1—C2—C3—C80.0 (2)C9—C10—N2—C11176.86 (18)
C9—C2—C3—C8176.91 (19)C15—C14—N3—C171.4 (4)
C8—C3—C4—C50.8 (3)C15—C14—N3—S1155.3 (3)
C2—C3—C4—C5177.6 (2)C16—C17—N3—C144.5 (4)
C3—C4—C5—C61.3 (3)C16—C17—N3—S1158.6 (2)
C3—C4—C5—C13179.18 (18)C14—N3—S1—O2169.3 (2)
C4—C5—C6—C70.8 (3)C17—N3—S1—O239.3 (3)
C13—C5—C6—C7179.7 (2)C14—N3—S1—O140.0 (2)
C5—C6—C7—C80.4 (3)C17—N3—S1—O1168.5 (2)
C6—C7—C8—N1178.3 (2)C14—N3—S1—C1374.8 (2)
C6—C7—C8—C30.9 (3)C17—N3—S1—C1376.6 (2)
C4—C3—C8—N1179.05 (17)C5—C13—S1—O259.60 (18)
C2—C3—C8—N10.2 (2)C5—C13—S1—O170.15 (18)
C4—C3—C8—C70.3 (3)C5—C13—S1—N3174.81 (15)
C2—C3—C8—C7179.17 (19)O3—C18—C19—C2071.6 (3)
C1—C2—C9—C1022.9 (3)O4—C18—C19—C20109.1 (2)
C3—C2—C9—C10160.94 (19)C18—C19—C20—O560.5 (2)
C2—C9—C10—N2165.28 (17)C18—C19—C20—C21177.14 (17)
C4—C5—C13—S1100.7 (2)O5—C20—C21—O75.1 (3)
C6—C5—C13—S179.8 (2)C19—C20—C21—O7117.3 (2)
N3—C14—C15—C162.5 (5)O5—C20—C21—O6174.6 (2)
C14—C15—C16—C175.4 (5)C19—C20—C21—O663.0 (3)
C15—C16—C17—N35.9 (4)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1N···O3i0.81 (2)2.39 (3)3.034 (3)138 (2)
N1—H1N···O60.81 (2)2.47 (2)3.087 (2)135 (2)
N2—H2N···O5ii0.86 (2)1.88 (2)2.731 (2)173 (2)
O4—H4O···O6iii0.83 (1)1.67 (1)2.503 (2)178 (4)
O5—H5O···O70.80 (3)2.11 (3)2.623 (2)122 (3)
O5—H5O···O7iv0.80 (3)2.19 (3)2.811 (2)135 (3)
C11—H11C···O4v0.962.383.276 (3)156
C14—H14A···O1vi0.972.553.301 (3)134
C11—H11B···Cg1iii0.962.873.819 (3)172
C12—H12A···Cg2iii0.962.833.767 (3)164
C13—H13A···Cg2vii0.972.913.577 (1)127
Symmetry codes: (i) x1, 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.

Experimental details

(I)(II)
Crystal data
Chemical formulaC17H25N3O2SC17H26N3O2S+·C4H5O5
Mr335.46469.55
Crystal system, space groupMonoclinic, C2/cTriclinic, P1
Temperature (K)294294
a, b, c (Å)20.5023 (17), 7.6894 (6), 22.8470 (19)7.5542 (7), 9.3561 (9), 17.3608 (17)
α, β, γ (°)90, 104.904 (2), 90104.081 (2), 101.121 (2), 92.681 (2)
V3)3480.7 (5)1162.13 (19)
Z82
Radiation typeMo KαMo Kα
µ (mm1)0.200.19
Crystal size (mm)0.22 × 0.16 × 0.090.19 × 0.14 × 0.08
Data collection
DiffractometerBruker SMART APEX CCD area-detector
diffractometer
Bruker SMART APEX CCD area-detector
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
16157, 3057, 2285 11188, 4062, 3743
Rint0.0680.017
(sin θ/λ)max1)0.5950.595
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.078, 0.162, 1.17 0.049, 0.133, 1.03
No. of reflections30574062
No. of parameters214307
No. of restraints02
H-atom treatmentH atoms treated by a mixture of independent and constrained refinementH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.37, 0.240.43, 0.33

Computer programs: SMART (Bruker, 2001), SAINT (Bruker, 2001), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), SHELXTL/PC (Sheldrick, 1990) and PLATON (Spek, 2003).

Selected geometric parameters (Å, º) for (I) top
C1—C21.356 (4)C10—N21.472 (4)
C2—C91.499 (5)C13—S11.782 (4)
C5—C131.499 (4)N3—S11.598 (3)
C8—N11.356 (4)
C8—N1—C1108.9 (3)C12—N2—C10109.7 (3)
C11—N2—C12109.3 (3)C14—N3—C17111.0 (3)
C11—N2—C10111.0 (3)N3—S1—C13108.02 (17)
C2—C9—C10—N2169.3 (3)C4—C5—C13—S192.2 (4)
Hydrogen-bond geometry (Å, º) for (I) top
D—H···AD—HH···AD···AD—H···A
N1—H1N···N2i0.80 (3)2.12 (3)2.906 (4)167 (3)
C15—H15B···Cg2ii0.972.963.909 (5)166
Symmetry codes: (i) x, y+1, z; (ii) x, y1, z1/2.
Selected geometric parameters (Å, º) for (II) top
C1—C21.367 (3)C10—N21.499 (3)
C2—C91.499 (3)C13—S11.791 (2)
C5—C131.509 (3)N3—S11.6064 (18)
C8—N11.364 (3)C19—C201.505 (3)
C8—N1—C1108.96 (18)C11—N2—C10111.52 (17)
C12—N2—C11110.40 (17)C14—N3—C17111.4 (2)
C12—N2—C10114.21 (17)N3—S1—C13106.52 (10)
C18—C19—C20—C21177.14 (17)
Hydrogen-bond geometry (Å, º) for (II) top
D—H···AD—HH···AD···AD—H···A
N1—H1N···O3i0.81 (2)2.39 (3)3.034 (3)138 (2)
N1—H1N···O60.81 (2)2.47 (2)3.087 (2)135 (2)
N2—H2N···O5ii0.86 (2)1.88 (2)2.731 (2)173 (2)
O4—H4O···O6iii0.83 (1)1.67 (1)2.503 (2)178 (4)
O5—H5O···O70.80 (3)2.11 (3)2.623 (2)122 (3)
O5—H5O···O7iv0.80 (3)2.19 (3)2.811 (2)135 (3)
C11—H11C···O4v0.962.383.276 (3)156
C14—H14A···O1vi0.972.553.301 (3)134
C11—H11B···Cg1iii0.962.873.819 (3)172
C12—H12A···Cg2iii0.962.833.767 (3)164
C13—H13A···Cg2vii0.972.913.577 (1)127
Symmetry codes: (i) x1, 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.
Solid-state comformation of triptans indicated by torsion angles τ1 and τ2 top
Refτ1 (°)τ2 (°)
1-23.7 (6)59.3 (3)
222.9 (3)-174.8 (2)
33.1 (4)-179.6 (2)
4-112.1 (1)-177.1 (2)
5-108.8 (3)-65.8 (3)*
6-100.5 (2)85.4 (2)**
(1) Almotriptan free base (I) (this work);

(2) almotriptan malate (II) (this work);

(3) sumatriptan free base (Ravikumar et al., 2006);

(4) sumatriptan succinate (Ravikumar et al., 2004);

(5) zomitriptan (Ravikumar et al., 2007a);

(6) rizatriptan benzoate (Ravikumar et al., 2007b).

* C—C—C—N and ** C—C—N—N.
 

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