Rupatadine.

IN THE TITLE COMPOUND (SYSTEMATIC NAME: 8-chloro-11-{1-[(5-methyl-pyridin-3-yl)meth-yl]piperidin-4-yl-idene}-6,11-di-hydro-5H-benzo[5,6]cyclo-hepta-[1,2-b]pyridine), C26H26ClN3, the dihedral angle between the mean planes of the chloro-phenyl and cyclo-hepta-[1,2-b]pyridinyl rings fused to the cyclo-heptane ring is 56.6 (1)°. The mean planes of the cyclo-hepta-[1,2-b]pyridinyl and 5-methyl-pyridin-3-yl rings are twisted by 64.9 (4)°. The central piperizene group is in a slightly distorted chair configuration. A weak intra-molecular C-H⋯N inter-action is observed between the cyclo-hepta-[1,2-b]pyridinyl and piperidin-4-yl-idene moieties.

Related literature

For the pharmacological importance of rupatadine, see: Kean & Plosker (2007 ▶); Merlos et al. (1997 ▶); Mullol et al. (2008 ▶); Picado (2006 ▶). For the reported synthesis methodology of rupatadine, see: Agarwal et al. (2008 ▶). For standard bond lengths, see: Allen et al. (1987 ▶).

Experimental

Crystal data

C26H26ClN3

M = 415.95

Monoclinic,

a = 10.2655 (3) Å

b = 11.3341 (4) Å

c = 18.8111 (6) Å

β = 90.874 (3)°

V = 2188.43 (11) Å3

Z = 4

Cu Kα radiation

μ = 1.67 mm−1

T = 173 K

0.42 × 0.38 × 0.22 mm

Data collection

Agilent Xcalibur (Eos, Gemini) diffractometer

Absorption correction: multi-scan (CrysAlis PRO and CrysAlis RED; Agilent, 2012 ▶) T min = 0.673, T max = 1.000

13849 measured reflections

4281 independent reflections

3565 reflections with I > 2σ(I)

R int = 0.026

Refinement

R[F 2 > 2σ(F 2)] = 0.041

wR(F 2) = 0.122

S = 1.05

4281 reflections

273 parameters

H-atom parameters constrained

Δρmax = 0.22 e Å−3

Δρmin = −0.29 e Å−3

Data collection: CrysAlis PRO (Agilent, 2012 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis RED (Agilent, 2012 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL2012 (Sheldrick, 2008 ▶); molecular graphics: OLEX2 (Dolomanov et al., 2009 ▶); software used to prepare material for publication: OLEX2.

Click here for additional data file.

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536813014256/hg5317sup1.cif

Click here for additional data file.

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813014256/hg5317Isup2.hkl

Click here for additional data file.

Supplementary material file. DOI: 10.1107/S1600536813014256/hg5317Isup3.cml

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

C26H26ClN3	F(000) = 880
Mr = 415.95	Dx = 1.262 Mg m−3
Monoclinic, P21/n	Cu Kα radiation, λ = 1.5418 Å
a = 10.2655 (3) Å	Cell parameters from 4864 reflections
b = 11.3341 (4) Å	θ = 3.9–72.2°
c = 18.8111 (6) Å	µ = 1.67 mm−1
β = 90.874 (3)°	T = 173 K
V = 2188.43 (11) Å3	Irregular, clear orangish orange
Z = 4	0.42 × 0.38 × 0.22 mm

Agilent Xcalibur (Eos, Gemini) diffractometer	4281 independent reflections
Radiation source: Enhance (Cu) X-ray Source	3565 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.026
Detector resolution: 16.0416 pixels mm-1	θmax = 72.4°, θmin = 4.6°
ω scans	h = −11→12
Absorption correction: multi-scan (CrysAlis PRO and CrysAlis RED; Agilent, 2012)	k = −8→13
Tmin = 0.673, Tmax = 1.000	l = −21→23
13849 measured reflections

Refinement on F2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F2 > 2σ(F2)] = 0.041	w = 1/[σ2(Fo2) + (0.0616P)2 + 0.3876P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.122	(Δ/σ)max < 0.001
S = 1.05	Δρmax = 0.22 e Å−3
4281 reflections	Δρmin = −0.29 e Å−3
273 parameters	Extinction correction: SHELXL2012 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 restraints	Extinction coefficient: 0.0043 (3)
Primary atom site location: structure-invariant direct methods

Experimental. (HPLC purity 99.75 %) FT IR (KBr) : 1350.2, 1475.6, 1583.6; 1H NMR (300 MHz, DMSO d6) δ 2.072 (s, 1H), 2.127-2.164 (m, 3H), 2.247 (s, 3H), 2.264-2.320 (m, 2H), 2.545-2.580 (m, 2H), 2.725-2.827 (m, 2H), 3.217-3.324 (m, 2H), 3.406 (s, 2H), 7.011-7.038 (d, 1H), 7.124-7.193 (m, 2H), 7.242-7.248 (d, 1H), 7.474-7.537 (m, 2H), 8.250-8.313 (dd, 3H); MS m/z (EI): 416 (M + 1).

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

	x	y	z	Uiso*/Ueq
Cl1	0.21448 (5)	0.23499 (6)	0.09566 (3)	0.0826 (2)
N1	0.76596 (13)	0.40249 (13)	0.35326 (7)	0.0484 (3)
N2	0.98891 (11)	0.58991 (11)	0.10639 (6)	0.0391 (3)
N3	1.29611 (17)	0.88557 (15)	0.14524 (10)	0.0684 (5)
C1	0.69993 (14)	0.44001 (13)	0.23053 (7)	0.0386 (3)
C2	0.69596 (14)	0.46981 (14)	0.30801 (8)	0.0399 (3)
C3	0.61966 (15)	0.56496 (14)	0.32955 (8)	0.0443 (4)
C4	0.54486 (17)	0.63427 (15)	0.27422 (9)	0.0509 (4)
H4A	0.6038	0.6550	0.2350	0.061*
H4B	0.5137	0.7087	0.2956	0.061*
C5	0.42840 (16)	0.56586 (15)	0.24409 (9)	0.0487 (4)
H5A	0.3693	0.5488	0.2839	0.058*
H5B	0.3808	0.6187	0.2108	0.058*
C6	0.45366 (15)	0.45093 (14)	0.20564 (8)	0.0425 (3)
C7	0.57478 (14)	0.39337 (14)	0.19947 (7)	0.0394 (3)
C8	0.76056 (19)	0.43009 (18)	0.42245 (9)	0.0576 (5)
H8	0.8101	0.3838	0.4552	0.069*
C9	0.6876 (2)	0.52139 (19)	0.44884 (9)	0.0626 (5)
H9	0.6863	0.5373	0.4984	0.075*
C10	0.61619 (18)	0.58930 (16)	0.40146 (9)	0.0558 (4)
H10	0.5647	0.6528	0.4183	0.067*
C11	0.34414 (16)	0.39908 (17)	0.17349 (9)	0.0519 (4)
H11	0.2620	0.4371	0.1767	0.062*
C12	0.35305 (16)	0.29398 (17)	0.13731 (9)	0.0531 (4)
C13	0.46934 (18)	0.23397 (16)	0.13272 (9)	0.0525 (4)
H13	0.4744	0.1604	0.1087	0.063*
C14	0.57883 (16)	0.28467 (15)	0.16437 (8)	0.0456 (4)
H14	0.6596	0.2440	0.1621	0.055*
C15	0.80824 (14)	0.45528 (14)	0.19264 (8)	0.0401 (3)
C16	0.81702 (16)	0.43718 (15)	0.11334 (8)	0.0468 (4)
H16A	0.7302	0.4154	0.0938	0.056*
H16B	0.8778	0.3716	0.1035	0.056*
C17	0.86446 (14)	0.54878 (15)	0.07714 (8)	0.0446 (4)
H17A	0.8738	0.5333	0.0257	0.053*
H17B	0.7984	0.6116	0.0826	0.053*
C18	0.97594 (15)	0.61314 (15)	0.18277 (8)	0.0445 (4)
H18A	0.9108	0.6764	0.1897	0.053*
H18B	1.0604	0.6412	0.2024	0.053*
C19	0.93417 (14)	0.50352 (15)	0.22298 (8)	0.0440 (4)
H19A	1.0030	0.4426	0.2199	0.053*
H19B	0.9227	0.5233	0.2738	0.053*
C20	1.02633 (15)	0.69742 (15)	0.06862 (8)	0.0462 (4)
H20A	0.9631	0.7606	0.0795	0.055*
H20B	1.0215	0.6823	0.0168	0.055*
C21	1.16119 (15)	0.73962 (13)	0.08791 (8)	0.0412 (3)
C22	1.17979 (18)	0.84145 (16)	0.12707 (10)	0.0566 (4)
H22	1.1046	0.8829	0.1421	0.068*
C23	1.39933 (18)	0.82602 (18)	0.12289 (10)	0.0604 (5)
H23	1.4831	0.8563	0.1350	0.072*
C24	1.39372 (16)	0.72266 (16)	0.08313 (9)	0.0485 (4)
C25	1.27098 (15)	0.67932 (15)	0.06625 (8)	0.0432 (3)
H25	1.2621	0.6083	0.0398	0.052*
C26	1.51532 (18)	0.6591 (2)	0.06151 (12)	0.0698 (6)
H26A	1.5056	0.5745	0.0709	0.105*
H26B	1.5899	0.6897	0.0889	0.105*
H26C	1.5297	0.6715	0.0107	0.105*

	U11	U22	U33	U12	U13	U23
Cl1	0.0574 (3)	0.1179 (5)	0.0722 (3)	−0.0312 (3)	−0.0097 (2)	−0.0091 (3)
N1	0.0462 (7)	0.0604 (8)	0.0386 (7)	0.0055 (6)	0.0025 (5)	0.0016 (6)
N2	0.0342 (6)	0.0489 (7)	0.0344 (6)	−0.0019 (5)	0.0044 (5)	−0.0008 (5)
N3	0.0712 (11)	0.0625 (10)	0.0716 (11)	−0.0165 (8)	0.0050 (8)	−0.0175 (8)
C1	0.0391 (7)	0.0420 (8)	0.0349 (7)	−0.0004 (6)	0.0034 (6)	0.0015 (6)
C2	0.0383 (7)	0.0460 (8)	0.0356 (7)	−0.0052 (6)	0.0056 (6)	0.0020 (6)
C3	0.0457 (8)	0.0445 (8)	0.0430 (8)	−0.0044 (7)	0.0067 (6)	−0.0008 (7)
C4	0.0605 (10)	0.0402 (8)	0.0523 (9)	0.0026 (7)	0.0079 (7)	0.0035 (7)
C5	0.0476 (9)	0.0516 (9)	0.0469 (9)	0.0087 (7)	0.0051 (7)	0.0107 (7)
C6	0.0408 (8)	0.0505 (9)	0.0364 (7)	−0.0010 (6)	0.0049 (6)	0.0099 (6)
C7	0.0396 (7)	0.0459 (8)	0.0330 (7)	−0.0040 (6)	0.0050 (6)	0.0063 (6)
C8	0.0623 (11)	0.0736 (12)	0.0367 (8)	0.0052 (9)	−0.0012 (7)	0.0043 (8)
C9	0.0730 (12)	0.0789 (13)	0.0362 (8)	0.0016 (10)	0.0048 (8)	−0.0107 (8)
C10	0.0629 (11)	0.0555 (10)	0.0493 (9)	0.0025 (8)	0.0084 (8)	−0.0122 (8)
C11	0.0392 (8)	0.0706 (11)	0.0459 (9)	−0.0030 (7)	0.0033 (7)	0.0087 (8)
C12	0.0449 (9)	0.0717 (12)	0.0427 (8)	−0.0173 (8)	−0.0017 (7)	0.0056 (8)
C13	0.0598 (10)	0.0542 (10)	0.0435 (9)	−0.0123 (8)	0.0018 (7)	−0.0012 (7)
C14	0.0449 (8)	0.0495 (9)	0.0426 (8)	−0.0014 (7)	0.0037 (6)	0.0019 (7)
C15	0.0386 (7)	0.0457 (8)	0.0360 (7)	−0.0022 (6)	0.0034 (6)	−0.0008 (6)
C16	0.0451 (8)	0.0584 (10)	0.0370 (8)	−0.0105 (7)	0.0075 (6)	−0.0078 (7)
C17	0.0387 (8)	0.0608 (10)	0.0343 (7)	−0.0050 (7)	0.0030 (6)	−0.0020 (7)
C18	0.0418 (8)	0.0552 (9)	0.0364 (7)	−0.0072 (7)	0.0024 (6)	−0.0051 (7)
C19	0.0394 (8)	0.0564 (9)	0.0364 (7)	−0.0036 (7)	0.0023 (6)	0.0012 (7)
C20	0.0411 (8)	0.0540 (9)	0.0436 (8)	−0.0003 (7)	0.0021 (6)	0.0062 (7)
C21	0.0443 (8)	0.0447 (8)	0.0348 (7)	−0.0038 (6)	0.0048 (6)	0.0052 (6)
C22	0.0586 (10)	0.0550 (10)	0.0563 (10)	−0.0035 (8)	0.0110 (8)	−0.0088 (8)
C23	0.0531 (10)	0.0690 (12)	0.0589 (10)	−0.0227 (9)	−0.0024 (8)	0.0007 (9)
C24	0.0437 (8)	0.0598 (10)	0.0420 (8)	−0.0050 (7)	0.0037 (6)	0.0096 (7)
C25	0.0470 (8)	0.0472 (8)	0.0356 (7)	−0.0027 (7)	0.0021 (6)	0.0007 (6)
C26	0.0456 (10)	0.0882 (15)	0.0758 (13)	0.0045 (10)	0.0078 (9)	0.0121 (11)

Cl1—C12	1.7465 (17)	C12—C13	1.378 (3)
N1—C2	1.343 (2)	C13—H13	0.9500
N1—C8	1.340 (2)	C13—C14	1.388 (2)
N2—C17	1.4597 (18)	C14—H14	0.9500
N2—C18	1.4688 (18)	C15—C16	1.510 (2)
N2—C20	1.465 (2)	C15—C19	1.508 (2)
N3—C22	1.334 (2)	C16—H16A	0.9900
N3—C23	1.330 (3)	C16—H16B	0.9900
C1—C2	1.4973 (19)	C16—C17	1.520 (2)
C1—C7	1.499 (2)	C17—H17A	0.9900
C1—C15	1.341 (2)	C17—H17B	0.9900
C2—C3	1.397 (2)	C18—H18A	0.9900
C3—C4	1.505 (2)	C18—H18B	0.9900
C3—C10	1.382 (2)	C18—C19	1.520 (2)
C4—H4A	0.9900	C19—H19A	0.9900
C4—H4B	0.9900	C19—H19B	0.9900
C4—C5	1.527 (2)	C20—H20A	0.9900
C5—H5A	0.9900	C20—H20B	0.9900
C5—H5B	0.9900	C20—C21	1.504 (2)
C5—C6	1.514 (2)	C21—C22	1.381 (2)
C6—C7	1.411 (2)	C21—C25	1.385 (2)
C6—C11	1.398 (2)	C22—H22	0.9500
C7—C14	1.399 (2)	C23—H23	0.9500
C8—H8	0.9500	C23—C24	1.391 (3)
C8—C9	1.375 (3)	C24—C25	1.385 (2)
C9—H9	0.9500	C24—C26	1.503 (2)
C9—C10	1.380 (3)	C25—H25	0.9500
C10—H10	0.9500	C26—H26A	0.9800
C11—H11	0.9500	C26—H26B	0.9800
C11—C12	1.376 (3)	C26—H26C	0.9800
C8—N1—C2	116.94 (15)	C1—C15—C19	123.97 (13)
C17—N2—C18	109.52 (11)	C19—C15—C16	111.07 (12)
C17—N2—C20	108.51 (12)	C15—C16—H16A	109.5
C20—N2—C18	110.72 (12)	C15—C16—H16B	109.5
C23—N3—C22	116.29 (16)	C15—C16—C17	110.72 (13)
C2—C1—C7	115.02 (12)	H16A—C16—H16B	108.1
C15—C1—C2	121.55 (13)	C17—C16—H16A	109.5
C15—C1—C7	123.42 (13)	C17—C16—H16B	109.5
N1—C2—C1	117.81 (13)	N2—C17—C16	112.43 (13)
N1—C2—C3	123.49 (14)	N2—C17—H17A	109.1
C3—C2—C1	118.70 (14)	N2—C17—H17B	109.1
C2—C3—C4	119.01 (14)	C16—C17—H17A	109.1
C10—C3—C2	117.46 (15)	C16—C17—H17B	109.1
C10—C3—C4	123.53 (15)	H17A—C17—H17B	107.9
C3—C4—H4A	109.1	N2—C18—H18A	109.3
C3—C4—H4B	109.1	N2—C18—H18B	109.3
C3—C4—C5	112.33 (13)	N2—C18—C19	111.77 (13)
H4A—C4—H4B	107.9	H18A—C18—H18B	107.9
C5—C4—H4A	109.1	C19—C18—H18A	109.3
C5—C4—H4B	109.1	C19—C18—H18B	109.3
C4—C5—H5A	107.7	C15—C19—C18	110.78 (13)
C4—C5—H5B	107.7	C15—C19—H19A	109.5
H5A—C5—H5B	107.1	C15—C19—H19B	109.5
C6—C5—C4	118.39 (13)	C18—C19—H19A	109.5
C6—C5—H5A	107.7	C18—C19—H19B	109.5
C6—C5—H5B	107.7	H19A—C19—H19B	108.1
C7—C6—C5	126.49 (14)	N2—C20—H20A	108.9
C11—C6—C5	115.21 (14)	N2—C20—H20B	108.9
C11—C6—C7	118.30 (15)	N2—C20—C21	113.25 (12)
C6—C7—C1	123.78 (14)	H20A—C20—H20B	107.7
C14—C7—C1	117.58 (13)	C21—C20—H20A	108.9
C14—C7—C6	118.61 (14)	C21—C20—H20B	108.9
N1—C8—H8	118.1	C22—C21—C20	120.91 (15)
N1—C8—C9	123.86 (17)	C22—C21—C25	117.57 (15)
C9—C8—H8	118.1	C25—C21—C20	121.50 (14)
C8—C9—H9	120.9	N3—C22—C21	124.46 (17)
C8—C9—C10	118.27 (16)	N3—C22—H22	117.8
C10—C9—H9	120.9	C21—C22—H22	117.8
C3—C10—H10	120.0	N3—C23—H23	117.6
C9—C10—C3	119.98 (17)	N3—C23—C24	124.82 (16)
C9—C10—H10	120.0	C24—C23—H23	117.6
C6—C11—H11	119.4	C23—C24—C26	121.46 (17)
C12—C11—C6	121.26 (16)	C25—C24—C23	116.89 (16)
C12—C11—H11	119.4	C25—C24—C26	121.63 (17)
C11—C12—Cl1	119.57 (14)	C21—C25—C24	119.96 (15)
C11—C12—C13	121.51 (15)	C21—C25—H25	120.0
C13—C12—Cl1	118.91 (15)	C24—C25—H25	120.0
C12—C13—H13	121.1	C24—C26—H26A	109.5
C12—C13—C14	117.74 (17)	C24—C26—H26B	109.5
C14—C13—H13	121.1	C24—C26—H26C	109.5
C7—C14—H14	118.8	H26A—C26—H26B	109.5
C13—C14—C7	122.50 (16)	H26A—C26—H26C	109.5
C13—C14—H14	118.8	H26B—C26—H26C	109.5
C1—C15—C16	124.75 (14)
Cl1—C12—C13—C14	177.98 (13)	C7—C1—C15—C16	5.0 (2)
N1—C2—C3—C4	−179.86 (14)	C7—C1—C15—C19	179.20 (14)
N1—C2—C3—C10	−0.6 (2)	C7—C6—C11—C12	0.7 (2)
N1—C8—C9—C10	−0.4 (3)	C8—N1—C2—C1	−179.61 (14)
N2—C18—C19—C15	−56.69 (17)	C8—N1—C2—C3	0.0 (2)
N2—C20—C21—C22	−109.94 (17)	C8—C9—C10—C3	−0.2 (3)
N2—C20—C21—C25	71.12 (18)	C10—C3—C4—C5	−106.83 (19)
N3—C23—C24—C25	−0.3 (3)	C11—C6—C7—C1	179.20 (13)
N3—C23—C24—C26	−178.44 (19)	C11—C6—C7—C14	−2.9 (2)
C1—C2—C3—C4	−0.3 (2)	C11—C12—C13—C14	−1.7 (3)
C1—C2—C3—C10	179.00 (14)	C12—C13—C14—C7	−0.6 (2)
C1—C7—C14—C13	−179.02 (14)	C15—C1—C2—N1	−68.7 (2)
C1—C15—C16—C17	122.92 (17)	C15—C1—C2—C3	111.71 (17)
C1—C15—C19—C18	−122.30 (16)	C15—C1—C7—C6	−126.93 (17)
C2—N1—C8—C9	0.5 (3)	C15—C1—C7—C14	55.1 (2)
C2—C1—C7—C6	52.68 (19)	C15—C16—C17—N2	55.82 (17)
C2—C1—C7—C14	−125.27 (15)	C16—C15—C19—C18	52.61 (17)
C2—C1—C15—C16	−174.60 (14)	C17—N2—C18—C19	59.11 (16)
C2—C1—C15—C19	−0.4 (2)	C17—N2—C20—C21	−172.79 (13)
C2—C3—C4—C5	72.40 (19)	C18—N2—C17—C16	−58.83 (17)
C2—C3—C10—C9	0.7 (3)	C18—N2—C20—C21	66.99 (16)
C3—C4—C5—C6	−61.48 (19)	C19—C15—C16—C17	−51.94 (18)
C4—C3—C10—C9	179.93 (17)	C20—N2—C17—C16	−179.79 (13)
C4—C5—C6—C7	5.9 (2)	C20—N2—C18—C19	178.72 (12)
C4—C5—C6—C11	−173.99 (14)	C20—C21—C22—N3	−178.84 (17)
C5—C6—C7—C1	−0.7 (2)	C20—C21—C25—C24	178.02 (14)
C5—C6—C7—C14	177.28 (14)	C22—N3—C23—C24	−0.5 (3)
C5—C6—C11—C12	−179.44 (14)	C22—C21—C25—C24	−1.0 (2)
C6—C7—C14—C13	2.9 (2)	C23—N3—C22—C21	0.6 (3)
C6—C11—C12—Cl1	−178.00 (12)	C23—C24—C25—C21	1.0 (2)
C6—C11—C12—C13	1.6 (3)	C25—C21—C22—N3	0.1 (3)
C7—C1—C2—N1	111.69 (16)	C26—C24—C25—C21	179.15 (15)
C7—C1—C2—C3	−67.92 (18)

D—H···A	D—H	H···A	D···A	D—H···A
C19—H19B···N1	0.99	2.60	3.229 (2)	121

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C19—H19B⋯N1	0.99	2.60	3.229 (2)	121