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The crystal structures of almotriptan {systematic name:
N,
N-dimethyl-2-[5-(pyrrolidin-1-ylsulfonylmethyl)-1
H-indol-3-yl]ethanamine}, C
17H
25N
3O
2S, and almotriptan malate {systematic name:
N,
N-dimethyl-2-[5-(pyrrolidin-1-ylsulfonylmethyl)-1
H-indol-3-yl]ethanaminium malate, C
17H
26N
3O
2S
+·C
4H
5O
5−, 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
CCDC references: 677217; 677218
Crystals of (I) and (II) (SMS Pharma Research Centre, Hyderabad) suitable for
X-ray diffraction were obtained from a methanol solution.
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.
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).
(I)
N,
N-dimethyl-2-[5-(pyrrolidin-1-ylsulfonylmethyl)-1
H-
indol-3-yl]-ethanamine
top
Crystal data top
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) Å3 | 0.22 × 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 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 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)] = 0.078 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.162 | H 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 parameters | Δρmax = 0.37 e Å−3 |
0 restraints | Δρmin = −0.24 e Å−3 |
Crystal data top
C17H25N3O2S | V = 3480.7 (5) Å3 |
Mr = 335.46 | Z = 8 |
Monoclinic, C2/c | Mo Kα radiation |
a = 20.5023 (17) Å | µ = 0.20 mm−1 |
b = 7.6894 (6) Å | T = 294 K |
c = 22.8470 (19) Å | 0.22 × 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 reflections | Rint = 0.068 |
3057 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.078 | 0 restraints |
wR(F2) = 0.162 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.17 | Δρmax = 0.37 e Å−3 |
3057 reflections | Δρmin = −0.24 e Å−3 |
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 | 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 (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
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) top
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) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1N···N2i | 0.80 (3) | 2.12 (3) | 2.906 (4) | 167 (3) |
C15—H15B···Cg2ii | 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)-1
H-
indol-3-yl]-ethanaminium malate
top
Crystal data top
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) Å3 | |
Data collection top
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 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)] = 0.049 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.133 | H 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 parameters | Δρmax = 0.43 e Å−3 |
2 restraints | Δρmin = −0.33 e Å−3 |
Crystal data top
C17H26N3O2S+·C4H5O5− | γ = 92.681 (2)° |
Mr = 469.55 | V = 1162.13 (19) Å3 |
Triclinic, P1 | Z = 2 |
a = 7.5542 (7) Å | Mo Kα radiation |
b = 9.3561 (9) Å | µ = 0.19 mm−1 |
c = 17.3608 (17) Å | T = 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 reflections | Rint = 0.017 |
4062 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.049 | 2 restraints |
wR(F2) = 0.133 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.03 | Δρmax = 0.43 e Å−3 |
4062 reflections | Δρmin = −0.33 e Å−3 |
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 | 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 (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
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) top
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) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1N···O3i | 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···O5ii | 0.86 (2) | 1.88 (2) | 2.731 (2) | 173 (2) |
O4—H4O···O6iii | 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···O7iv | 0.80 (3) | 2.19 (3) | 2.811 (2) | 135 (3) |
C11—H11C···O4v | 0.96 | 2.38 | 3.276 (3) | 156 |
C14—H14A···O1vi | 0.97 | 2.55 | 3.301 (3) | 134 |
C11—H11B···Cg1iii | 0.96 | 2.87 | 3.819 (3) | 172 |
C12—H12A···Cg2iii | 0.96 | 2.83 | 3.767 (3) | 164 |
C13—H13A···Cg2vii | 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. |
Experimental details
| (I) | (II) |
Crystal data |
Chemical formula | C17H25N3O2S | C17H26N3O2S+·C4H5O5− |
Mr | 335.46 | 469.55 |
Crystal system, space group | Monoclinic, C2/c | Triclinic, P1 |
Temperature (K) | 294 | 294 |
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), 90 | 104.081 (2), 101.121 (2), 92.681 (2) |
V (Å3) | 3480.7 (5) | 1162.13 (19) |
Z | 8 | 2 |
Radiation type | Mo Kα | Mo Kα |
µ (mm−1) | 0.20 | 0.19 |
Crystal size (mm) | 0.22 × 0.16 × 0.09 | 0.19 × 0.14 × 0.08 |
|
Data collection |
Diffractometer | Bruker 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 |
Rint | 0.068 | 0.017 |
(sin θ/λ)max (Å−1) | 0.595 | 0.595 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.078, 0.162, 1.17 | 0.049, 0.133, 1.03 |
No. of reflections | 3057 | 4062 |
No. of parameters | 214 | 307 |
No. of restraints | 0 | 2 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.37, −0.24 | 0.43, −0.33 |
Selected geometric parameters (Å, º) for (I) topC1—C2 | 1.356 (4) | C10—N2 | 1.472 (4) |
C2—C9 | 1.499 (5) | C13—S1 | 1.782 (4) |
C5—C13 | 1.499 (4) | N3—S1 | 1.598 (3) |
C8—N1 | 1.356 (4) | | |
| | | |
C8—N1—C1 | 108.9 (3) | C12—N2—C10 | 109.7 (3) |
C11—N2—C12 | 109.3 (3) | C14—N3—C17 | 111.0 (3) |
C11—N2—C10 | 111.0 (3) | N3—S1—C13 | 108.02 (17) |
| | | |
C2—C9—C10—N2 | 169.3 (3) | C4—C5—C13—S1 | −92.2 (4) |
Hydrogen-bond geometry (Å, º) for (I) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1N···N2i | 0.80 (3) | 2.12 (3) | 2.906 (4) | 167 (3) |
C15—H15B···Cg2ii | 0.97 | 2.96 | 3.909 (5) | 166 |
Symmetry codes: (i) x, y+1, z; (ii) x, −y−1, z−1/2. |
Selected geometric parameters (Å, º) for (II) topC1—C2 | 1.367 (3) | C10—N2 | 1.499 (3) |
C2—C9 | 1.499 (3) | C13—S1 | 1.791 (2) |
C5—C13 | 1.509 (3) | N3—S1 | 1.6064 (18) |
C8—N1 | 1.364 (3) | C19—C20 | 1.505 (3) |
| | | |
C8—N1—C1 | 108.96 (18) | C11—N2—C10 | 111.52 (17) |
C12—N2—C11 | 110.40 (17) | C14—N3—C17 | 111.4 (2) |
C12—N2—C10 | 114.21 (17) | N3—S1—C13 | 106.52 (10) |
| | | |
C18—C19—C20—C21 | −177.14 (17) | | |
Hydrogen-bond geometry (Å, º) for (II) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1N···O3i | 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···O5ii | 0.86 (2) | 1.88 (2) | 2.731 (2) | 173 (2) |
O4—H4O···O6iii | 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···O7iv | 0.80 (3) | 2.19 (3) | 2.811 (2) | 135 (3) |
C11—H11C···O4v | 0.96 | 2.38 | 3.276 (3) | 156 |
C14—H14A···O1vi | 0.97 | 2.55 | 3.301 (3) | 134 |
C11—H11B···Cg1iii | 0.96 | 2.87 | 3.819 (3) | 172 |
C12—H12A···Cg2iii | 0.96 | 2.83 | 3.767 (3) | 164 |
C13—H13A···Cg2vii | 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. |
Solid-state comformation of triptans indicated by torsion angles
τ1 and τ2 topRef | τ1 (°) | τ2 (°) |
1 | -23.7 (6) | 59.3 (3) |
2 | 22.9 (3) | -174.8 (2) |
3 | 3.1 (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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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).