Rupatadine

Kaur, M.; Jasinski, J.P.; Luopa, Z.A.; Kumar, N.; Patel, N.G.; Gudaparthi, O.; Yathirajan, H.S.

doi:10.1107/S1600536813014256

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 69| Part 6| June 2013| Page o980

doi:10.1107/S1600536813014256

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Rupatadine

Manpreet Kaur,^a Jerry P. Jasinski,^b ^* Zane A. Luopa,^b Neeraj Kumar,^c Nilesh G. Patel,^c Omprakash Gudaparthi ^c and H. S. Yathirajan ^a

^aDepartment of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, India, ^bDepartment of Chemistry, Keene State College, 229 Main Street, Keene, NH 03435-2001, USA, and ^cCR & D, Cadila Pharmaceuticals Ltd, 1389, Trasad Road, Dholka, Ahmedabad 387 810, Gujarat, India
^*Correspondence e-mail: jjasinski@keene.edu

(Received 21 May 2013; accepted 22 May 2013; online 31 May 2013)

In the title compound (systematic name: 8-chloro-11-{1-[(5-methylpyridin-3-yl)methyl]piperidin-4-ylidene}-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine), C₂₆H₂₆ClN₃, the dihedral angle between the mean planes of the chlorophenyl and cyclohepta[1,2-b]pyridinyl rings fused to the cycloheptane ring is 56.6 (1)°. The mean planes of the cyclohepta[1,2-b]pyridinyl and 5-methylpyridin-3-yl rings are twisted by 64.9 (4)°. The central piperizene group is in a slightly distorted chair configuration. A weak intramolecular C—H⋯N interaction is observed between the cyclohepta[1,2-b]pyridinyl and piperidin-4-ylidene 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_r = 415.95
Monoclinic, P 2₁ /n
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[F² > 2σ(F²)] = 0.041
wR(F²) = 0.122
S = 1.05
4281 reflections
273 parameters
H-atom parameters constrained
Δρ_max = 0.22 e Å⁻³
Δρ_min = −0.29 e Å⁻³

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

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.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536813014256/hg5317sup1.cif

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

Supporting information file. DOI: 10.1107/S1600536813014256/hg5317Isup3.cml

checkCIF report

Comment top

Rupatadine (IUPAC Name: 8-Chloro-6,11-dihydro-11-[1-[(5-methyl-3- pyridinyl) methyl]-4-piperidinylidene]-5H-benzo[5,6]cyclohepta[1,2-b] pyridine) is a non-sedating antihistamine showing a rapid onset of action and a good safety profile even in prolonged treatment periods of a year (Picado, 2006; Mullol et al., 2008). A review of its use in the management of allergic disorders is published (Kean & Plosker, 2007). Rupatadine has shown as inhibition deregulation, induced by the immunological and non-immunological stimulants and the inhibition of release of cytokines, particularly the tumor necrosis factor alpha (TNF-alpha) in human mastocytes and monocytes (Picado, 2006). In vitro metabolism studies indicate that rupatadine is metabolized mainly by the cytochrome P-450 in liver (Merlos et al., 1997). In view of the importance of the title compound, (I), C₂₆H₂₆ClN₃, we have synthesized rupatadine free base based on a reported method (Agarwal et al., 2008) and its single crystal structure is reported herin.

In (I), the dihedral angle between the mean planes of the chlorophenyl and cyclohepta[1,2-b]pyridinyl rings fused to the cycloheptane ring is 56.6 (1)° (Fig. 1). The mean planes of the cyclohepta[1,2-b]pyridinyl and 5-methyl-3-pyridinyl rings are twisted by 64.9 (4)°. The central 6-membered piperizene group adopts a slightly distorted chair configuration with puckering parameters Q, θ and ϕ of 0.5613 (16)Å, 3.31 (16)°, and 348 (3)°, respectively. A weak C—H···O intramolecular interaction is observed between the cyclohepta[1,2-b]pyridinyl and 4-piperidinylidene moieties. In the crystal, the molecules pack in a normal head-to tail dimer-like arrangement (Fig. 2).

Related literature top

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 top

4-methyl-3-chloromethyl pyridine hydrochloride (3.5 g, 0.02 mol), desloratadine (6.2 g, 0.02 mol), potassium carbonate (6.9 g, 0.05 mol) was charged into acetonitrile (30 ml) Fig. 3). The reaction mass was heated to 313–318 K and stirred for 10-12 h (Agarwal et al., 2008). The reaction mass was cooled to 298–303 K and the inorganic material filtered. The solvent was removed under reduced pressure. Toluene (40 ml) was added to residue and heated to 328-333 K to get a clear solution. The toluene layer was washed with a saturated sodium chloride solution (40 ml) and water (25 ml). Half the quantity of toluene was distilled out under vacuum and single crystals were grown from toluene using the slow evaporation technique (m. p.: 409–410 K).

Computing details top

Data collection: CrysAlis PRO (Agilent, 2012); cell refinement: CrysAlis PRO (Agilent, 2012); 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 (Dolomanov et al., 2009).

Figures top

	Fig. 1. Molecular structure of the title compound showing the atom labeling scheme and 30% probability displacement ellipsoids.
	Fig. 2. Packing diagram of the title compound viewed along the b axis.
	Fig. 3. Reaction scheme for the synthesis of rupatadine free base.

8-Chloro-11-{1-[(5-methylpyridin-3-yl)methyl]piperidin-4-ylidene}-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine top

Crystal data top

C₂₆H₂₆ClN₃	F(000) = 880
M_r = 415.95	D_x = 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

Data collection top

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

Refinement top

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(F_o²) + (0.0616P)² + 0.3876P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.122	(Δ/σ)_max < 0.001
S = 1.05	Δρ_max = 0.22 e Å⁻³
4281 reflections	Δρ_min = −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

Crystal data top

C₂₆H₂₆ClN₃	V = 2188.43 (11) Å³
M_r = 415.95	Z = 4
Monoclinic, P2₁/n	Cu Kα radiation
a = 10.2655 (3) Å	µ = 1.67 mm⁻¹
b = 11.3341 (4) Å	T = 173 K
c = 18.8111 (6) Å	0.42 × 0.38 × 0.22 mm
β = 90.874 (3)°

Data collection top

Agilent Xcalibur (Eos, Gemini) diffractometer	4281 independent reflections
Absorption correction: multi-scan (CrysAlis PRO and CrysAlis RED; Agilent, 2012)	3565 reflections with I > 2σ(I)
T_min = 0.673, T_max = 1.000	R_int = 0.026
13849 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.041	0 restraints
wR(F²) = 0.122	H-atom parameters constrained
S = 1.05	Δρ_max = 0.22 e Å⁻³
4281 reflections	Δρ_min = −0.29 e Å⁻³
273 parameters

Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
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*

Atomic displacement parameters (Å²) top

	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)

Geometric parameters (Å, º) top

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)

Hydrogen-bond geometry (Å, º) top

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

Experimental details

Crystal data
Chemical formula	C₂₆H₂₆ClN₃
M_r	415.95
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	173
a, b, c (Å)	10.2655 (3), 11.3341 (4), 18.8111 (6)
β (°)	90.874 (3)
V (Å³)	2188.43 (11)
Z	4
Radiation type	Cu Kα
µ (mm⁻¹)	1.67
Crystal size (mm)	0.42 × 0.38 × 0.22

Data collection
Diffractometer	Agilent Xcalibur (Eos, Gemini) diffractometer
Absorption correction	Multi-scan (CrysAlis PRO and CrysAlis RED; Agilent, 2012)
T_min, T_max	0.673, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	13849, 4281, 3565
R_int	0.026
(sin θ/λ)_max (Å⁻¹)	0.618

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.041, 0.122, 1.05
No. of reflections	4281
No. of parameters	273
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.22, −0.29

Computer programs: CrysAlis PRO (Agilent, 2012), CrysAlis RED (Agilent, 2012), SHELXS97 (Sheldrick, 2008), SHELXL2012 (Sheldrick, 2008), OLEX2 (Dolomanov et al., 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C19—H19B···N1	0.99	2.60	3.229 (2)	121.3

Acknowledgements

HSY thanks the UOM for research facilities. JPJ acknowledges the NSF–MRI program (grant No. CHE-1039027) for funds to purchase the X-ray diffractometer.

References

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