Rizatriptan benzoate, a drug for the treatment of migraine headache

Rizatriptan benzoate [systematic name: N,N-dimethyl-3-[5-(1H-1,2,4-triazol-1-ylmeth­yl)-1H-indol-3-yl]ethanaminium benzoate], C₁₅H₂₀N₅⁺·C₇H₅O₂^-, is a selective serotonin receptor agonist. Bond lengths and angles are similar to those of sumatriptan and zolmitriptan, but the three compounds differ in their side-chain orientations. The benzoate anion acts as an acceptor for hydrogen bonds from rizatriptan cations, forming hydrogen-bonded chains running along the b axis.

Key indicators

• Single-crystal X-ray study
• T = 294 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.047
• wR factor = 0.128
• Data-to-parameter ratio = 13.4

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT241_ALERT_2_C Check High      Ueq as Compared to Neighbors for        C13
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for         N2
PLAT244_ALERT_4_C Low   'Solvent' Ueq as Compared to Neighbors for        C22

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   3 ALERT level C = Check and explain
   0 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   2 ALERT type 2 Indicator that the structure model may be wrong or deficient
   0 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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Computing details

Data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003) and DIAMOND (Brandenburg & Putz, 2005); software used to prepare material for publication: SHELXL97.

N,N-dimethyl-3-[5-(1H-1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethanaminium benzoate

Crystal data

C15H20N5^+·C7H5O2^−	F(000) = 1664
Mr = 391.47	Dx = 1.254 Mg m^−3
Orthorhombic, Pbca	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 7359 reflections
a = 8.7405 (6) Å	θ = 2.7–22.6°
b = 21.3242 (15) Å	µ = 0.08 mm^−1
c = 22.2434 (16) Å	T = 294 K
V = 4145.8 (5) Å^3	Block, colorless
Z = 8	0.19 × 0.16 × 0.12 mm

Data collection

Bruker SMART CCD area-detector diffractometer	2837 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.033
Graphite monochromator	θmax = 25.0°, θmin = 1.8°
ω scans	h = −10→10
37507 measured reflections	k = −25→25
3656 independent reflections	l = −26→26

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)] = 0.047	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.128	H atoms treated by a mixture of independent and constrained refinement
S = 1.02	w = 1/[σ^2(Fo^2) + (0.0595P)^2 + 1.1036P] where P = (Fo^2 + 2Fc^2)/3
3656 reflections	(Δ/σ)max < 0.001
272 parameters	Δρmax = 0.22 e Å^−3
0 restraints	Δρmin = −0.16 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	0.3627 (2)	0.14409 (9)	0.52599 (8)	0.0606 (5)
H1	0.4155	0.1442	0.4897	0.073*
C2	0.2964 (2)	0.19524 (8)	0.55139 (8)	0.0529 (4)
C3	0.22811 (19)	0.17437 (8)	0.60634 (7)	0.0490 (4)
C4	0.1429 (2)	0.20357 (9)	0.65153 (8)	0.0545 (5)
H4	0.1211	0.2462	0.6490	0.065*
C5	0.0914 (2)	0.16942 (10)	0.69959 (8)	0.0599 (5)
C6	0.1263 (2)	0.10541 (11)	0.70322 (9)	0.0686 (6)
H6	0.0924	0.0828	0.7364	0.082*
C7	0.2086 (3)	0.07495 (10)	0.65975 (9)	0.0674 (6)
H7	0.2301	0.0324	0.6628	0.081*
C8	0.2586 (2)	0.10978 (8)	0.61100 (8)	0.0546 (4)
C9	0.2970 (2)	0.26122 (8)	0.52867 (8)	0.0608 (5)
H9A	0.1962	0.2794	0.5341	0.073*
H9B	0.3196	0.2611	0.4860	0.073*
C10	0.4139 (2)	0.30119 (8)	0.56104 (9)	0.0574 (5)
H10A	0.4113	0.2913	0.6036	0.069*
H10B	0.5152	0.2909	0.5461	0.069*
C11	0.3945 (3)	0.38985 (10)	0.49003 (10)	0.0799 (7)
H11A	0.4962	0.3832	0.4750	0.120*
H11B	0.3696	0.4336	0.4875	0.120*
H11C	0.3231	0.3661	0.4664	0.120*
C12	0.4889 (3)	0.40690 (11)	0.59171 (13)	0.0983 (8)
H12A	0.5930	0.4011	0.5791	0.147*
H12B	0.4781	0.3935	0.6327	0.147*
H12C	0.4621	0.4504	0.5886	0.147*
C13	−0.0007 (2)	0.19956 (12)	0.74906 (10)	0.0779 (6)
H13A	−0.0475	0.2376	0.7338	0.093*
H13B	−0.0821	0.1713	0.7610	0.093*
C14	0.1238 (3)	0.18039 (11)	0.84876 (9)	0.0682 (6)
H14	0.0826	0.1409	0.8562	0.082*
C15	0.2449 (3)	0.26241 (13)	0.85517 (11)	0.0811 (7)
H15	0.3108	0.2930	0.8699	0.097*
N1	0.3409 (2)	0.09264 (8)	0.56112 (8)	0.0650 (5)
H1N	0.369 (2)	0.0543 (11)	0.5530 (10)	0.077 (7)*
N2	0.3865 (2)	0.36939 (7)	0.55293 (7)	0.0577 (4)
H2N	0.285 (3)	0.3775 (9)	0.5682 (9)	0.070 (6)*
N3	0.1697 (2)	0.26964 (9)	0.80497 (9)	0.0771 (5)
N4	0.2215 (2)	0.20858 (11)	0.88396 (8)	0.0816 (6)
N5	0.09096 (17)	0.21488 (8)	0.80142 (7)	0.0603 (4)
C16	−0.0700 (2)	0.44769 (8)	0.63779 (9)	0.0545 (5)
C17	−0.1084 (2)	0.41486 (10)	0.68884 (9)	0.0675 (5)
H17	−0.0509	0.3801	0.7000	0.081*
C18	−0.2319 (3)	0.43299 (12)	0.72395 (10)	0.0781 (6)
H18	−0.2569	0.4106	0.7584	0.094*
C19	−0.3165 (3)	0.48409 (11)	0.70745 (11)	0.0802 (7)
H19	−0.3997	0.4963	0.7307	0.096*
C20	−0.2797 (2)	0.51736 (11)	0.65686 (12)	0.0788 (6)
H20	−0.3375	0.5522	0.6460	0.095*
C21	−0.1570 (2)	0.49934 (9)	0.62197 (10)	0.0670 (5)
H21	−0.1325	0.5220	0.5876	0.080*
C22	0.0635 (2)	0.42822 (9)	0.59952 (9)	0.0590 (5)
O1	0.1207 (2)	0.37585 (7)	0.61054 (8)	0.0931 (5)
O2	0.10865 (18)	0.46262 (7)	0.55864 (7)	0.0791 (5)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0702 (13)	0.0616 (12)	0.0502 (11)	0.0009 (10)	−0.0014 (9)	−0.0068 (9)
C2	0.0606 (11)	0.0524 (10)	0.0457 (9)	0.0009 (8)	−0.0088 (8)	−0.0020 (8)
C3	0.0478 (10)	0.0528 (10)	0.0465 (9)	−0.0005 (8)	−0.0122 (8)	−0.0023 (8)
C4	0.0479 (10)	0.0637 (11)	0.0520 (10)	0.0061 (8)	−0.0109 (8)	−0.0017 (9)
C5	0.0408 (9)	0.0853 (15)	0.0538 (11)	−0.0048 (9)	−0.0085 (8)	0.0022 (10)
C6	0.0633 (12)	0.0832 (15)	0.0593 (12)	−0.0245 (11)	−0.0077 (10)	0.0112 (11)
C7	0.0778 (14)	0.0544 (11)	0.0700 (13)	−0.0139 (10)	−0.0159 (11)	0.0066 (10)
C8	0.0554 (10)	0.0527 (10)	0.0556 (10)	−0.0045 (8)	−0.0129 (9)	−0.0033 (9)
C9	0.0778 (13)	0.0590 (12)	0.0456 (10)	0.0018 (10)	−0.0092 (9)	0.0020 (8)
C10	0.0566 (11)	0.0564 (11)	0.0591 (11)	0.0077 (9)	−0.0038 (9)	0.0010 (9)
C11	0.0992 (18)	0.0627 (13)	0.0779 (15)	0.0040 (12)	0.0128 (13)	0.0127 (11)
C12	0.0988 (19)	0.0722 (15)	0.124 (2)	−0.0117 (14)	−0.0288 (16)	−0.0214 (14)
C13	0.0453 (10)	0.1254 (19)	0.0630 (12)	0.0072 (12)	0.0004 (10)	0.0035 (13)
C14	0.0754 (14)	0.0739 (14)	0.0551 (12)	0.0080 (11)	0.0055 (11)	0.0024 (10)
C15	0.0728 (14)	0.1022 (19)	0.0683 (14)	−0.0042 (13)	0.0131 (12)	−0.0267 (14)
N1	0.0788 (12)	0.0498 (10)	0.0663 (11)	0.0053 (9)	−0.0062 (9)	−0.0093 (8)
N2	0.0564 (10)	0.0531 (9)	0.0637 (10)	0.0049 (7)	0.0011 (8)	−0.0062 (7)
N3	0.0811 (12)	0.0775 (13)	0.0727 (12)	−0.0031 (10)	0.0196 (10)	0.0019 (9)
N4	0.0820 (13)	0.1060 (16)	0.0566 (10)	0.0165 (12)	−0.0031 (10)	−0.0119 (11)
N5	0.0502 (9)	0.0798 (11)	0.0508 (9)	0.0077 (8)	0.0073 (7)	0.0037 (8)
C16	0.0510 (10)	0.0449 (10)	0.0676 (12)	−0.0030 (8)	−0.0032 (9)	−0.0147 (9)
C17	0.0643 (12)	0.0653 (13)	0.0729 (13)	0.0023 (10)	−0.0045 (11)	−0.0096 (11)
C18	0.0738 (14)	0.0893 (16)	0.0712 (13)	−0.0078 (13)	0.0070 (12)	−0.0085 (12)
C19	0.0596 (12)	0.0821 (16)	0.0988 (18)	0.0011 (12)	0.0107 (13)	−0.0266 (14)
C20	0.0597 (13)	0.0635 (13)	0.1132 (19)	0.0078 (10)	0.0074 (13)	−0.0099 (13)
C21	0.0578 (11)	0.0527 (11)	0.0905 (15)	0.0005 (9)	0.0054 (11)	−0.0066 (10)
C22	0.0606 (11)	0.0447 (10)	0.0718 (13)	0.0004 (9)	−0.0028 (10)	−0.0163 (10)
O1	0.0999 (12)	0.0719 (10)	0.1075 (12)	0.0363 (9)	0.0292 (10)	0.0121 (9)
O2	0.0880 (11)	0.0564 (8)	0.0930 (11)	0.0048 (7)	0.0254 (9)	−0.0029 (8)

Geometric parameters (Å, º)

C1—C2	1.358 (3)	C12—H12B	0.9600
C1—N1	1.360 (3)	C12—H12C	0.9600
C1—H1	0.9300	C13—N5	1.451 (3)
C2—C3	1.431 (2)	C13—H13A	0.9700
C2—C9	1.495 (2)	C13—H13B	0.9700
C3—C4	1.398 (2)	C14—N4	1.305 (3)
C3—C8	1.407 (2)	C14—N5	1.316 (3)
C4—C5	1.370 (3)	C14—H14	0.9300
C4—H4	0.9300	C15—N3	1.305 (3)
C5—C6	1.401 (3)	C15—N4	1.330 (3)
C5—C13	1.507 (3)	C15—H15	0.9300
C6—C7	1.369 (3)	N1—H1N	0.87 (2)
C6—H6	0.9300	N2—H2N	0.97 (2)
C7—C8	1.385 (3)	N3—N5	1.358 (2)
C7—H7	0.9300	C16—C17	1.376 (3)
C8—N1	1.372 (2)	C16—C21	1.384 (3)
C9—C10	1.513 (3)	C16—C22	1.503 (3)
C9—H9A	0.9700	C17—C18	1.387 (3)
C9—H9B	0.9700	C17—H17	0.9300
C10—N2	1.485 (2)	C18—C19	1.367 (3)
C10—H10A	0.9700	C18—H18	0.9300
C10—H10B	0.9700	C19—C20	1.369 (3)
C11—N2	1.467 (3)	C19—H19	0.9300
C11—H11A	0.9600	C20—C21	1.378 (3)
C11—H11B	0.9600	C20—H20	0.9300
C11—H11C	0.9600	C21—H21	0.9300
C12—N2	1.478 (3)	C22—O2	1.233 (2)
C12—H12A	0.9600	C22—O1	1.248 (2)
C2—C1—N1	110.44 (17)	N5—C13—C5	112.80 (15)
C2—C1—H1	124.8	N5—C13—H13A	109.0
N1—C1—H1	124.8	C5—C13—H13A	109.0
C1—C2—C3	106.48 (16)	N5—C13—H13B	109.0
C1—C2—C9	127.84 (17)	C5—C13—H13B	109.0
C3—C2—C9	125.66 (16)	H13A—C13—H13B	107.8
C4—C3—C8	118.96 (17)	N4—C14—N5	111.4 (2)
C4—C3—C2	134.27 (17)	N4—C14—H14	124.3
C8—C3—C2	106.76 (16)	N5—C14—H14	124.3
C5—C4—C3	119.98 (18)	N3—C15—N4	115.9 (2)
C5—C4—H4	120.0	N3—C15—H15	122.1
C3—C4—H4	120.0	N4—C15—H15	122.1
C4—C5—C6	119.42 (19)	C1—N1—C8	108.84 (16)
C4—C5—C13	121.2 (2)	C1—N1—H1N	126.9 (14)
C6—C5—C13	119.33 (19)	C8—N1—H1N	124.2 (14)
C7—C6—C5	122.42 (19)	C11—N2—C12	111.52 (19)
C7—C6—H6	118.8	C11—N2—C10	113.53 (15)
C5—C6—H6	118.8	C12—N2—C10	111.20 (16)
C6—C7—C8	117.67 (19)	C11—N2—H2N	109.0 (12)
C6—C7—H7	121.2	C12—N2—H2N	104.8 (12)
C8—C7—H7	121.2	C10—N2—H2N	106.3 (11)
N1—C8—C7	130.98 (18)	C15—N3—N5	101.74 (19)
N1—C8—C3	107.49 (16)	C14—N4—C15	102.08 (19)
C7—C8—C3	121.52 (18)	C14—N5—N3	108.88 (18)
C2—C9—C10	111.84 (15)	C14—N5—C13	129.6 (2)
C2—C9—H9A	109.2	N3—N5—C13	121.34 (18)
C10—C9—H9A	109.2	C17—C16—C21	118.75 (19)
C2—C9—H9B	109.2	C17—C16—C22	121.09 (18)
C10—C9—H9B	109.2	C21—C16—C22	120.16 (19)
H9A—C9—H9B	107.9	C16—C17—C18	120.8 (2)
N2—C10—C9	112.66 (15)	C16—C17—H17	119.6
N2—C10—H10A	109.1	C18—C17—H17	119.6
C9—C10—H10A	109.1	C19—C18—C17	119.5 (2)
N2—C10—H10B	109.1	C19—C18—H18	120.3
C9—C10—H10B	109.1	C17—C18—H18	120.3
H10A—C10—H10B	107.8	C18—C19—C20	120.4 (2)
N2—C11—H11A	109.5	C18—C19—H19	119.8
N2—C11—H11B	109.5	C20—C19—H19	119.8
H11A—C11—H11B	109.5	C19—C20—C21	120.1 (2)
N2—C11—H11C	109.5	C19—C20—H20	120.0
H11A—C11—H11C	109.5	C21—C20—H20	120.0
H11B—C11—H11C	109.5	C20—C21—C16	120.4 (2)
N2—C12—H12A	109.5	C20—C21—H21	119.8
N2—C12—H12B	109.5	C16—C21—H21	119.8
H12A—C12—H12B	109.5	O2—C22—O1	123.29 (19)
N2—C12—H12C	109.5	O2—C22—C16	120.12 (18)
H12A—C12—H12C	109.5	O1—C22—C16	116.57 (19)
H12B—C12—H12C	109.5
N1—C1—C2—C3	0.0 (2)	C7—C8—N1—C1	−179.58 (19)
N1—C1—C2—C9	178.08 (18)	C3—C8—N1—C1	0.1 (2)
C1—C2—C3—C4	−178.89 (19)	C9—C10—N2—C11	−61.2 (2)
C9—C2—C3—C4	2.9 (3)	C9—C10—N2—C12	172.10 (19)
C1—C2—C3—C8	0.11 (19)	N4—C15—N3—N5	−0.2 (2)
C9—C2—C3—C8	−178.06 (17)	N5—C14—N4—C15	0.4 (2)
C8—C3—C4—C5	0.5 (2)	N3—C15—N4—C14	−0.1 (3)
C2—C3—C4—C5	179.37 (18)	N4—C14—N5—N3	−0.5 (2)
C3—C4—C5—C6	0.7 (3)	N4—C14—N5—C13	174.08 (18)
C3—C4—C5—C13	179.93 (16)	C15—N3—N5—C14	0.4 (2)
C4—C5—C6—C7	−1.2 (3)	C15—N3—N5—C13	−174.73 (17)
C13—C5—C6—C7	179.58 (18)	C5—C13—N5—C14	−88.6 (3)
C5—C6—C7—C8	0.4 (3)	C5—C13—N5—N3	85.4 (2)
C6—C7—C8—N1	−179.55 (19)	C21—C16—C17—C18	0.0 (3)
C6—C7—C8—C3	0.8 (3)	C22—C16—C17—C18	−179.91 (18)
C4—C3—C8—N1	179.04 (15)	C16—C17—C18—C19	0.1 (3)
C2—C3—C8—N1	−0.14 (19)	C17—C18—C19—C20	−0.3 (3)
C4—C3—C8—C7	−1.2 (3)	C18—C19—C20—C21	0.3 (3)
C2—C3—C8—C7	179.60 (16)	C19—C20—C21—C16	−0.1 (3)
C1—C2—C9—C10	−100.5 (2)	C17—C16—C21—C20	0.0 (3)
C3—C2—C9—C10	77.2 (2)	C22—C16—C21—C20	179.91 (18)
C2—C9—C10—N2	−162.93 (16)	C17—C16—C22—O2	−170.43 (18)
C4—C5—C13—N5	−99.1 (2)	C21—C16—C22—O2	9.7 (3)
C6—C5—C13—N5	80.2 (2)	C17—C16—C22—O1	11.4 (3)
C2—C1—N1—C8	0.0 (2)	C21—C16—C22—O1	−168.46 (19)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···O2^i	0.87 (2)	1.97 (2)	2.808 (2)	161 (2)
N2—H2N···O1	0.97 (2)	1.72 (2)	2.657 (2)	163 (2)
N2—H2N···O2	0.97 (2)	2.39 (2)	3.141 (2)	134 (2)
C9—H9B···N4^ii	0.97	2.51	3.349 (2)	145
C11—H11C···N4^ii	0.96	2.59	3.502 (3)	159

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