15-(4-Chloro­phen­yl)-6b-hy­droxy-17-methyl-6b,7,16,17-tetra­hydro-7,14a-methano­naphtho[1′,8′:1,2,3]pyrrolo­[3′,2′:8,8a]azuleno[5,6-b]quinolin-14(15H)-one methanol hemisolvate

Joseph, J.M.; Viswanathan, V.; Velmurugan, D.

doi:10.1107/S2414314616006374

organic compounds

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ISSN: 2414-3146

Volume 1| Part 4| April 2016| x160637

doi:10.1107/S2414314616006374

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15-(4-Chlorophenyl)-6b-hydroxy-17-methyl-6b,7,16,17-tetrahydro-7,14a-methanonaphtho[1′,8′:1,2,3]pyrrolo[3′,2′:8,8a]azuleno[5,6-b]quinolin-14(15H)-one methanol hemisolvate

J. M. Joseph,^a Vijayan Viswanathan ^a and Devadasan Velmurugan ^a ^*

^aCentre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600 025, India
^*Correspondence e-mail: shirai2011@gmail.com

Edited by H. Stoeckli-Evans, University of Neuchâtel, Switzerland (Received 2 April 2016; accepted 15 April 2016; online 29 April 2016)

In the title solvate, C₃₅H₂₅ClN₂O₃·0.5CH₃OH, the conformation of the central 1-methylpyrrolidine ring is best described as an envelope with the N atom as the flap. The cyclopentane ring adopts a twist conformation on the CH—CH₂ bond and the cyclohexane ring has an envelope conformation with the CH₂ atom as the flap. The pyrrolidine ring makes dihedral angles of 40.87 (12), 67.89 (11), 81.86 (9) and 70.86 (12)° with the mean planes of the cyclopentane, cyclohexane, acenaphthylene and chlorobenzene rings, respectively. The quinoline ring system is inclined to the naphthalene ring system by 54.14 (6)°. There is a short O—H⋯N contact in the molecule making an S(5) ring motif. In the crystal, there is a disordered and partially occupied ethan-1,2-diol solvent molecule present, located about an inversion centre, which links the title molecules via O—H⋯O and C—H⋯O hydrogen bonds, forming chains propagating along the a-axis direction.

Keywords: crystal structure; pyrrolidine; quinoline; acenaphthylene; hydrogen bonding.

CCDC reference: 1474273

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Chemical scheme

Structure description

The pyrrolidine ring system is found in a vast variety of compounds displaying an impressive range of biological activities (Babu et al., 2012 ). Optically active pyrrolidines have been used as intermediates, chiral ligands or auxiliaries in controlled asymmetric synthesis (Savithri et al., 2014 ). Pyrrolidine compounds are reported to exhibit antimicrobial, antifungal (Govind et al.,2003 ), anti-influenza virus A (Stylianakis et al., 2003 ), anti-inflammatory and antitumor (Li & Xu, 2004 ) activities. They also inhibit retroviral reverse transcriptases [i.e., human immunodeficiency virus type 1 (HIV-1)], cellular DNA polymerases, protein kinases (Bellina & Rossi, 2006 ). They also act as antidepressant agents (Wróbel et al., 2013 ), antibiotics (Nirmala et al., 2009 ), anticonvulsant, sphingosine-1-phosphate (S1P) receptor agonists, malic enzyme inhibitors, ketoamide-based cathepsin K inhibitors and human melanocortin-4 receptor agonists (Babu et al., 2012). Quinoline derivatives have been synthesized and explored for their analgesic activity, anti-allergetic properties and in treating Alzheimer's disease (AD). They are also reported for their anticancer, antitinephritic, antitumor, anti-inflammatory (Shivaraj et al., 2013 ), antimalarial, anti-bacterial and antifungal activities (Marella et al., 2013 ).

The molecular structure of the title compound is shown in Fig. 1. In the molecule there is a short intramolecular O—H⋯N contact forming an S(5) ring motif (Fig. 1 and Table 1). The conformation of the central 1-methyl pyrrolidine ring (C12/C14/N2/C26/C27) is best described as an envelope with atom N2 as the flap and displaced by 0.585 (2) Å from the plane through the other four atoms. The cyclopentane ring adopts a twist conformation on the C10—C11 bond and the cyclohexane ring has an envelope conformation with atom C11 as the flap and displaced by 0.854 (2) Å from the mean plane through the other five atoms. The quinoline ring system (C1–C9/N1) and the acenaphthylene ring system (C14–C25) adopt almost planar conformations, with the maximum deviations being 0.069 (2) Å for atom C8 in the quinoline ring system and 0.128 (2) Å for atom C14 in the acenaphthylene ring system. Chlorine atom Cl1 is displaced from the benzene ring (C28–C33) to which it is attached by 0.0164 (8) Å. The mean plane of the pyrrolidine ring makes dihedral angles of 40.87 (12), 67.89 (11), 81.86 (9) and 70.86 (12)° with the mean planes of the cyclopentane, cyclohexane, acenaphthylene and chlorobenzene rings, respectively. The quinoline ring system is inclined to the naphthalene ring system by 54.14 (6)°.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3O⋯N1	0.82	2.28	2.984 (4)	145
O2—H2O⋯N2	0.87 (3)	2.20 (3)	2.695 (2)	116 (2)
O2—H2O⋯O3ⁱ	0.87 (3)	2.26 (3)	3.021 (5)	146 (2)
C33—H33⋯O3ⁱ	0.93	2.53	3.408 (6)	157
Symmetry code: (i) -x+1, -y+1, -z+1.

Figure 1
The molecular structure of the title compound, showing the atom labelling and displacement ellipsoids drawn at the 30% probability level. The O—H⋯N contact is shown as a thin dashed line (see Table 1

In the crystal, there is a disordered and partially occupied ethan-1,2-diol solvent molecule present, located about an inversion centre, which links the title molecules via O—H⋯O and C—H⋯O hydrogen bonds, forming chains propagating along the a-axis direction. (Table 1 and Fig. 2).

Figure 2
The crystal packing of the title compound viewed along the b axis. Hydrogen bonds are shown as dashed lines (see Table 1

). For clarity, only one position of the disordered and partially occupied ethan-1,2-diol solvent molecule is shown.

Synthesis and crystallization

A mixture of (E)-2-(4-chlorobenzylidene)-3,4-dihydroacridin-1(2H)-one (1 mmol), acenaphthoquinone (1 mmol) and sarcosine (1.5 mmol) was heated to reflux in toluene (3 ml) for 10 h. After completion of the reaction as evident from TLC, the reaction mixture was extracted with ethyl acetate (2 × 20 ml), washed with water (2 × 10 ml), dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. It was then subjected to column chromatography using petroleum ether–AcOEt (5:1 v/v) as eluent to obtain the title compound as a pure product. Colourless block-like crystals were prepared by slow evaporation of a solution of the title compound in ethanol at room temperature.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. The partially occupied methanol solvent molecule is disordered and located about an inversion centre (Fig. 1). The solvate molecule shows a high degree of disorder in such a way that the methyl carbon atom assumes four positions. Two are within the asymmetric unit, each with 0.25 occupancy, and the counterparts occupy symmetry-related positions, each with 0.25 occupancy. Similarly, the hydroxyl group assumes two positions with 0.5 occupancy. The hydrogen atoms could not be fixed on the carbon atom with agreeable geometry.

Table 2
Experimental details

Crystal data
Chemical formula	C₃₄H₂₅ClN₂O₂·0.5CH₄O
M_r	544.53
Crystal system, space group	Triclinic, P $[\overline{1}]$
Temperature (K)	293
a, b, c (Å)	10.3848 (3), 10.4306 (3), 14.4513 (4)
α, β, γ (°)	69.394 (1), 72.388 (1), 70.871 (1)
V (Å³)	1352.92 (7)
Z	2
Radiation type	Mo Kα
μ (mm⁻¹)	0.18
Crystal size (mm)	0.22 × 0.16 × 0.12

Data collection
Diffractometer	Bruker SMART APEXII area-detector
Absorption correction	Multi-scan (SADABS; Bruker, 2008 )
T_min, T_max	0.966, 0.978
No. of measured, independent and observed [I > 2σ(I)] reflections	20173, 5563, 4425
R_int	0.019
(sin θ/λ)_max (Å⁻¹)	0.629

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.052, 0.178, 1.05
No. of reflections	5563
No. of parameters	386
No. of restraints	3
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.66, −0.44
Computer programs: APEX2 and SAINT (Bruker, 2008), SHELXS97 (Sheldrick, 2008 ), SHELXL2014 (Sheldrick, 2015 ) and PLATON (Spek, 2009 ).

Structural data

CCDC reference: 1474273

Crystal structure: contains datablocks global, I. DOI: 10.1107/S2414314616006374/su4031sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S2414314616006374/su4031Isup2.hkl

Supporting information file. DOI: 10.1107/S2414314616006374/su4031Isup3.cml

checkCIF report

Experimental top

Structure description top

The pyrrolidine ring system is found in a vast variety of compounds displaying an impressive range of biological activities (Babu et al., 2012). Optically active pyrrolidines have been used as intermediates, chiral ligands or auxiliaries in controlled asymmetric synthesis (Savithri et al., 2014). Pyrrolidine compounds are reported to exhibit antimicrobial, antifungal (Govind et al.,2003), anti-influenza virus A (Stylianakis et al., 2003), anti-inflammatory and antitumor (Li & Xu, 2004) activities. They also inhibit retroviral reverse transcriptases [i.e., human immunodeficiency virus type 1 (HIV-1)], cellular DNA polymerases, protein kinases (Bellina & Rossi, 2006). They also act as antidepressant agents (Wróbel et al., 2013), antibiotics (Nirmala et al., 2009), anticonvulsant, sphingosine-1-phosphate (S1P) receptor agonists, malic enzyme inhibitors, ketoamide-based cathepsin K inhibitors and human melanocortin-4 receptor agonists (Babu et al., 2012). Quinoline derivatives have been synthesized and explored for their analgesic activity, anti-allergetic properties and in treating Alzheimer's disease (AD). They are also reported for their anticancer, antitinephritic, antitumor, anti-inflammatory (Shivaraj et al., 2013), antimalarial, anti-bacterial and antifungal activities (Marella et al., 2013).

The molecular structure of the title compound is shown in Fig. 1. In the molecule there is a short intramolecular O—H···N contact forming an S(5) ring motif (Fig. 1 and Table 1). The conformation of the central 1-methyl pyrrolidine ring (C12/C14/N2/C26/C27) is best described as an envelope conformation with atom N2 as the flap and displaced by 0.585 (2) Å from the plane through the other four atoms. The cyclopentane ring adopts a twist conformation on the C10—C11 bond and the cyclohexane ring has an envelope conformation with atom C11 as the flap and displaced by 0.854 (2) Å from the mean plane through the other five atoms. The quinoline ring system (C1–C9/N1) and the acenaphthylene ring system (C14–C25) adopt almost planar conformations, with the maximum deviations being 0.069 (2) Å for atom C8 in the quinoline ring system and 0.128 (2) Å for atom C14 in the acenaphthylene ring system. Chlorine atom Cl1 is displaced from the benzene ring (C28–C33) to which it is attached by 0.0164 (8) Å. The mean plane of the pyrrolidine ring makes dihedral angles of 40.87 (12), 67.89 (11), 81.86 (9) and 70.86 (12)° with the mean planes of the cyclopentane, cyclohexane, acenaphthylene and chlorobenzene rings, respectively. The quinoline ring system is inclined to the naphthalene ring system by 54.14 (6)°.

In the crystal, there is a disordered and partially occupied ethan-1,2-diol solvent molecule present, located about an inversion centre, which links the title molecules via O—H···O and C—H···O hydrogen bonds, forming chains propagating along the a-axis direction. (Table 1 and Fig. 2).

Computing details top

Data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015) and PLATON (Spek, 2009).

Figures top

	Fig. 1. The molecular structure of the title compound, showing the atom labelling and displacement ellipsoids drawn at the 30% probability level. The N—H···O contact is shown as a thin dashed lines(see Table 1).
	Fig. 2. The crystal packing of the title compound viewed along the b axis. Hydrogen bonds are shown as dashed lines (see Table 1). For clarity, only one position of the disordered and partially occupied ethan-1,2-diol solvent molecule is shown.

15-(4-Chlorophenyl)-6b-hydroxy-17-methyl-6b,7,16,17-tetrahydro- 7,14a-methanonaphtho[1',8':1,2,3]pyrrolo[3',2':8,8a]azuleno[5,6-b]quinolin-14(15H)-one methanol hemisolvate top

Crystal data top

C₃₄H₂₅ClN₂O₂·0.5CH₄O	Z = 2
M_r = 544.53	F(000) = 569
Triclinic, P1	D_x = 1.337 Mg m⁻³
a = 10.3848 (3) Å	Mo Kα radiation, λ = 0.71073 Å
b = 10.4306 (3) Å	Cell parameters from 5568 reflections
c = 14.4513 (4) Å	θ = 1.5–26.5°
α = 69.394 (1)°	µ = 0.18 mm⁻¹
β = 72.388 (1)°	T = 293 K
γ = 70.871 (1)°	Block, colourless
V = 1352.92 (7) Å³	0.22 × 0.16 × 0.12 mm

Data collection top

Bruker SMART APEXII area-detector diffractometer	4425 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.019
ω and φ scans	θ_max = 26.5°, θ_min = 1.5°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −13→13
T_min = 0.966, T_max = 0.978	k = −13→12
20173 measured reflections	l = −18→15
5563 independent reflections

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.052	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.178	w = 1/[σ²(F_o²) + (0.1116P)² + 0.2946P] where P = (F_o² + 2F_c²)/3
S = 1.05	(Δ/σ)_max < 0.001
5563 reflections	Δρ_max = 0.66 e Å⁻³
386 parameters	Δρ_min = −0.44 e Å⁻³
3 restraints	Extinction correction: SHELXL2014 (Sheldrick, 2015), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.019 (4)

Crystal data top

C₃₄H₂₅ClN₂O₂·0.5CH₄O	γ = 70.871 (1)°
M_r = 544.53	V = 1352.92 (7) Å³
Triclinic, P1	Z = 2
a = 10.3848 (3) Å	Mo Kα radiation
b = 10.4306 (3) Å	µ = 0.18 mm⁻¹
c = 14.4513 (4) Å	T = 293 K
α = 69.394 (1)°	0.22 × 0.16 × 0.12 mm
β = 72.388 (1)°

Data collection top

Bruker SMART APEXII area-detector diffractometer	5563 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2008)	4425 reflections with I > 2σ(I)
T_min = 0.966, T_max = 0.978	R_int = 0.019
20173 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.052	3 restraints
wR(F²) = 0.178	H atoms treated by a mixture of independent and constrained refinement
S = 1.05	Δρ_max = 0.66 e Å⁻³
5563 reflections	Δρ_min = −0.44 e Å⁻³
386 parameters

Special details top

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	Occ. (<1)
Cl1	0.72400 (8)	−0.21816 (7)	0.66553 (5)	0.0903 (3)
O1	0.58561 (15)	0.35178 (15)	0.13530 (11)	0.0563 (4)
O2	0.67317 (16)	0.59399 (18)	0.39571 (11)	0.0570 (4)
H2O	0.743 (3)	0.520 (3)	0.405 (2)	0.092 (10)*
N1	0.27834 (16)	0.70993 (17)	0.28663 (12)	0.0470 (4)
N2	0.84974 (15)	0.43617 (16)	0.27419 (13)	0.0472 (4)
C1	0.19626 (18)	0.75391 (19)	0.21738 (14)	0.0463 (4)
C2	0.0684 (2)	0.8558 (2)	0.23152 (19)	0.0626 (6)
H2	0.0427	0.8932	0.2860	0.075*
C3	−0.0175 (2)	0.8992 (3)	0.1653 (2)	0.0702 (6)
H3	−0.1023	0.9648	0.1760	0.084*
C4	0.0197 (2)	0.8469 (2)	0.08168 (19)	0.0634 (6)
H4	−0.0402	0.8778	0.0374	0.076*
C5	0.1428 (2)	0.7514 (2)	0.06473 (17)	0.0549 (5)
H5	0.1686	0.7199	0.0074	0.066*
C6	0.23238 (19)	0.69925 (19)	0.13379 (14)	0.0447 (4)
C7	0.35429 (19)	0.58980 (19)	0.12598 (14)	0.0440 (4)
H7	0.3811	0.5501	0.0725	0.053*
C8	0.43319 (17)	0.54205 (18)	0.19758 (13)	0.0391 (4)
C9	0.39312 (17)	0.60925 (18)	0.27596 (13)	0.0401 (4)
C10	0.48274 (18)	0.55891 (19)	0.35269 (13)	0.0423 (4)
H10	0.4294	0.5842	0.4151	0.051*
C11	0.54119 (19)	0.39953 (19)	0.37358 (13)	0.0448 (4)
H11A	0.4683	0.3517	0.3885	0.054*
H11B	0.5893	0.3612	0.4292	0.054*
C12	0.64345 (17)	0.38709 (17)	0.27249 (13)	0.0393 (4)
C13	0.55758 (18)	0.41925 (18)	0.19547 (13)	0.0402 (4)
C14	0.71568 (17)	0.51111 (17)	0.24384 (13)	0.0388 (4)
C15	0.61918 (18)	0.61159 (19)	0.31166 (13)	0.0414 (4)
C16	0.60670 (18)	0.75928 (19)	0.24087 (14)	0.0434 (4)
C17	0.5485 (2)	0.8893 (2)	0.25675 (18)	0.0569 (5)
H17	0.5065	0.8983	0.3216	0.068*
C18	0.5533 (3)	1.0098 (2)	0.1728 (2)	0.0694 (7)
H18	0.5162	1.0987	0.1837	0.083*
C19	0.6103 (2)	1.0011 (2)	0.0763 (2)	0.0663 (6)
H19	0.6108	1.0833	0.0230	0.080*
C20	0.66844 (19)	0.8680 (2)	0.05661 (16)	0.0525 (5)
C21	0.66716 (17)	0.74950 (18)	0.14204 (14)	0.0412 (4)
C22	0.72521 (17)	0.60975 (18)	0.13645 (13)	0.0410 (4)
C23	0.7808 (2)	0.5866 (2)	0.04288 (15)	0.0538 (5)
H23	0.8193	0.4952	0.0367	0.065*
C24	0.7782 (2)	0.7046 (3)	−0.04387 (16)	0.0638 (6)
H24	0.8132	0.6890	−0.1074	0.077*
C25	0.7264 (2)	0.8401 (3)	−0.03804 (17)	0.0638 (6)
H25	0.7294	0.9148	−0.0969	0.077*
C26	0.8953 (2)	0.3053 (2)	0.24478 (17)	0.0559 (5)
H26A	0.9666	0.2373	0.2800	0.067*
H26B	0.9325	0.3234	0.1725	0.067*
C27	0.76447 (19)	0.25010 (19)	0.27486 (15)	0.0463 (4)
H27	0.7655	0.2117	0.2217	0.056*
C28	0.75497 (19)	0.13475 (19)	0.37432 (15)	0.0458 (4)
C29	0.7023 (2)	0.0238 (2)	0.38486 (16)	0.0543 (5)
H29	0.6719	0.0224	0.3310	0.065*
C30	0.6933 (2)	−0.0857 (2)	0.47347 (18)	0.0632 (6)
H30	0.6583	−0.1601	0.4788	0.076*
C31	0.7367 (2)	−0.0827 (2)	0.55281 (17)	0.0589 (5)
C32	0.7896 (3)	0.0258 (3)	0.5450 (2)	0.0720 (7)
H32	0.8186	0.0273	0.5994	0.086*
C33	0.7997 (3)	0.1334 (2)	0.45517 (19)	0.0653 (6)
H33	0.8373	0.2060	0.4495	0.078*
C34	0.9561 (2)	0.5167 (2)	0.23428 (18)	0.0600 (5)
H34A	0.9804	0.5378	0.1619	0.090*
H34B	1.0375	0.4619	0.2615	0.090*
H34C	0.9203	0.6033	0.2533	0.090*
O3	0.1064 (5)	0.6190 (5)	0.4934 (3)	0.0885 (11)	0.5
H3O	0.1791	0.6313	0.4529	0.133*	0.5
C35A	0.0517 (15)	0.5293 (19)	0.4674 (10)	0.067 (3)	0.25
H35A	0.0192	0.5837	0.4053	0.080*	0.25
H35B	0.1295	0.4524	0.4515	0.080*	0.25
C35B	−0.0043 (14)	0.5733 (13)	0.4846 (11)	0.058 (3)	0.25
H35C	−0.0904	0.6180	0.5235	0.069*	0.25
H35D	−0.0121	0.6094	0.4143	0.069*	0.25

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.1073 (6)	0.0674 (4)	0.0697 (4)	−0.0169 (4)	−0.0261 (4)	0.0138 (3)
O1	0.0633 (8)	0.0546 (8)	0.0575 (8)	−0.0072 (6)	−0.0138 (7)	−0.0295 (7)
O2	0.0588 (8)	0.0722 (10)	0.0482 (8)	−0.0098 (8)	−0.0204 (6)	−0.0250 (7)
N1	0.0430 (8)	0.0512 (9)	0.0457 (9)	−0.0099 (7)	−0.0042 (6)	−0.0181 (7)
N2	0.0390 (7)	0.0422 (8)	0.0555 (9)	−0.0108 (6)	−0.0091 (6)	−0.0082 (7)
C1	0.0415 (9)	0.0444 (10)	0.0504 (10)	−0.0140 (7)	−0.0059 (8)	−0.0103 (8)
C2	0.0523 (11)	0.0584 (13)	0.0701 (14)	−0.0041 (9)	−0.0108 (10)	−0.0203 (11)
C3	0.0510 (11)	0.0571 (13)	0.0899 (18)	−0.0011 (10)	−0.0205 (11)	−0.0124 (12)
C4	0.0590 (12)	0.0553 (12)	0.0738 (15)	−0.0175 (10)	−0.0283 (11)	−0.0005 (11)
C5	0.0596 (11)	0.0518 (11)	0.0570 (12)	−0.0212 (9)	−0.0208 (9)	−0.0056 (9)
C6	0.0456 (9)	0.0437 (9)	0.0459 (10)	−0.0189 (7)	−0.0098 (7)	−0.0066 (7)
C7	0.0478 (9)	0.0475 (10)	0.0411 (9)	−0.0172 (8)	−0.0078 (7)	−0.0142 (8)
C8	0.0394 (8)	0.0415 (9)	0.0371 (9)	−0.0151 (7)	−0.0025 (7)	−0.0119 (7)
C9	0.0389 (8)	0.0440 (9)	0.0370 (8)	−0.0149 (7)	−0.0007 (7)	−0.0129 (7)
C10	0.0433 (9)	0.0513 (10)	0.0318 (8)	−0.0129 (7)	−0.0017 (7)	−0.0152 (7)
C11	0.0482 (9)	0.0481 (10)	0.0351 (9)	−0.0165 (8)	−0.0033 (7)	−0.0084 (7)
C12	0.0410 (8)	0.0356 (8)	0.0389 (9)	−0.0117 (7)	−0.0038 (7)	−0.0098 (7)
C13	0.0445 (9)	0.0410 (9)	0.0362 (8)	−0.0172 (7)	−0.0010 (7)	−0.0124 (7)
C14	0.0397 (8)	0.0374 (9)	0.0382 (9)	−0.0111 (7)	−0.0056 (7)	−0.0103 (7)
C15	0.0450 (9)	0.0469 (10)	0.0377 (9)	−0.0126 (7)	−0.0100 (7)	−0.0161 (7)
C16	0.0414 (9)	0.0432 (9)	0.0534 (10)	−0.0119 (7)	−0.0157 (7)	−0.0166 (8)
C17	0.0564 (11)	0.0514 (11)	0.0766 (14)	−0.0086 (9)	−0.0226 (10)	−0.0311 (10)
C18	0.0670 (13)	0.0395 (11)	0.111 (2)	−0.0067 (9)	−0.0369 (14)	−0.0227 (12)
C19	0.0595 (12)	0.0427 (11)	0.0920 (18)	−0.0165 (9)	−0.0333 (12)	0.0046 (11)
C20	0.0419 (9)	0.0486 (10)	0.0616 (12)	−0.0155 (8)	−0.0189 (8)	0.0015 (9)
C21	0.0379 (8)	0.0404 (9)	0.0475 (10)	−0.0138 (7)	−0.0127 (7)	−0.0080 (7)
C22	0.0396 (8)	0.0430 (9)	0.0384 (9)	−0.0147 (7)	−0.0039 (7)	−0.0087 (7)
C23	0.0514 (10)	0.0591 (12)	0.0447 (10)	−0.0176 (9)	0.0028 (8)	−0.0147 (9)
C24	0.0538 (11)	0.0867 (17)	0.0384 (10)	−0.0223 (11)	0.0010 (8)	−0.0075 (10)
C25	0.0507 (11)	0.0717 (15)	0.0512 (12)	−0.0220 (10)	−0.0124 (9)	0.0112 (10)
C26	0.0446 (10)	0.0438 (10)	0.0668 (13)	−0.0077 (8)	−0.0038 (9)	−0.0108 (9)
C27	0.0471 (9)	0.0386 (9)	0.0506 (10)	−0.0090 (7)	−0.0086 (8)	−0.0123 (8)
C28	0.0450 (9)	0.0375 (9)	0.0540 (10)	−0.0081 (7)	−0.0149 (8)	−0.0102 (8)
C29	0.0618 (11)	0.0492 (11)	0.0576 (12)	−0.0204 (9)	−0.0198 (9)	−0.0096 (9)
C30	0.0726 (14)	0.0496 (11)	0.0693 (14)	−0.0265 (10)	−0.0207 (11)	−0.0036 (10)
C31	0.0583 (12)	0.0464 (11)	0.0597 (12)	−0.0074 (9)	−0.0179 (10)	−0.0012 (9)
C32	0.0918 (17)	0.0656 (14)	0.0678 (15)	−0.0188 (13)	−0.0444 (13)	−0.0069 (11)
C33	0.0827 (15)	0.0525 (12)	0.0742 (15)	−0.0258 (11)	−0.0381 (12)	−0.0072 (10)
C34	0.0461 (10)	0.0555 (12)	0.0762 (15)	−0.0183 (9)	−0.0143 (10)	−0.0096 (10)
O3	0.105 (3)	0.113 (3)	0.058 (2)	−0.045 (3)	−0.0189 (19)	−0.018 (2)
C35A	0.076 (8)	0.089 (11)	0.057 (6)	−0.049 (8)	0.009 (7)	−0.039 (7)
C35B	0.061 (7)	0.045 (7)	0.060 (8)	0.005 (5)	−0.026 (6)	−0.012 (5)

Geometric parameters (Å, º) top

Cl1—C31	1.743 (2)	C18—C19	1.364 (4)
O1—C13	1.216 (2)	C18—H18	0.9300
O2—C15	1.418 (2)	C19—C20	1.413 (3)
O2—H2O	0.87 (3)	C19—H19	0.9300
N1—C9	1.315 (2)	C20—C21	1.407 (3)
N1—C1	1.369 (2)	C20—C25	1.409 (3)
N2—C26	1.460 (3)	C21—C22	1.404 (2)
N2—C34	1.463 (2)	C22—C23	1.373 (3)
N2—C14	1.469 (2)	C23—C24	1.414 (3)
C1—C6	1.413 (3)	C23—H23	0.9300
C1—C2	1.414 (3)	C24—C25	1.361 (4)
C2—C3	1.365 (3)	C24—H24	0.9300
C2—H2	0.9300	C25—H25	0.9300
C3—C4	1.396 (4)	C26—C27	1.531 (3)
C3—H3	0.9300	C26—H26A	0.9700
C4—C5	1.354 (3)	C26—H26B	0.9700
C4—H4	0.9300	C27—C28	1.516 (3)
C5—C6	1.416 (3)	C27—H27	0.9800
C5—H5	0.9300	C28—C33	1.376 (3)
C6—C7	1.406 (3)	C28—C29	1.379 (3)
C7—C8	1.369 (3)	C29—C30	1.386 (3)
C7—H7	0.9300	C29—H29	0.9300
C8—C9	1.425 (2)	C30—C31	1.366 (3)
C8—C13	1.493 (2)	C30—H30	0.9300
C9—C10	1.505 (2)	C31—C32	1.370 (3)
C10—C11	1.523 (3)	C32—C33	1.387 (3)
C10—C15	1.560 (2)	C32—H32	0.9300
C10—H10	0.9800	C33—H33	0.9300
C11—C12	1.544 (2)	C34—H34A	0.9600
C11—H11A	0.9700	C34—H34B	0.9600
C11—H11B	0.9700	C34—H34C	0.9600
C12—C13	1.513 (2)	O3—C35B	1.434 (15)
C12—C27	1.561 (2)	O3—C35A	1.437 (13)
C12—C14	1.574 (2)	O3—H3O	0.8200
C14—C22	1.525 (2)	C35A—C35Aⁱ	1.35 (3)
C14—C15	1.582 (2)	C35A—H35A	0.9700
C15—C16	1.509 (2)	C35A—H35B	0.9700
C16—C17	1.362 (3)	C35B—C35Bⁱ	1.41 (3)
C16—C21	1.401 (3)	C35B—H35C	0.9700
C17—C18	1.409 (3)	C35B—H35D	0.9700
C17—H17	0.9300

C15—O2—H2O	112 (2)	C19—C18—H18	118.8
C9—N1—C1	118.06 (15)	C17—C18—H18	118.8
C26—N2—C34	112.47 (16)	C18—C19—C20	120.5 (2)
C26—N2—C14	105.83 (15)	C18—C19—H19	119.7
C34—N2—C14	115.37 (15)	C20—C19—H19	119.7
N1—C1—C6	122.77 (17)	C21—C20—C25	116.39 (19)
N1—C1—C2	118.60 (18)	C21—C20—C19	115.8 (2)
C6—C1—C2	118.62 (19)	C25—C20—C19	127.8 (2)
C3—C2—C1	120.1 (2)	C16—C21—C22	113.43 (16)
C3—C2—H2	120.0	C16—C21—C20	123.31 (17)
C1—C2—H2	120.0	C22—C21—C20	123.25 (18)
C2—C3—C4	121.2 (2)	C23—C22—C21	118.69 (17)
C2—C3—H3	119.4	C23—C22—C14	132.84 (17)
C4—C3—H3	119.4	C21—C22—C14	108.43 (15)
C5—C4—C3	120.3 (2)	C22—C23—C24	118.6 (2)
C5—C4—H4	119.9	C22—C23—H23	120.7
C3—C4—H4	119.9	C24—C23—H23	120.7
C4—C5—C6	120.3 (2)	C25—C24—C23	122.5 (2)
C4—C5—H5	119.8	C25—C24—H24	118.7
C6—C5—H5	119.8	C23—C24—H24	118.7
C7—C6—C1	117.53 (17)	C24—C25—C20	120.43 (19)
C7—C6—C5	122.98 (18)	C24—C25—H25	119.8
C1—C6—C5	119.43 (18)	C20—C25—H25	119.8
C8—C7—C6	119.54 (17)	N2—C26—C27	105.35 (15)
C8—C7—H7	120.2	N2—C26—H26A	110.7
C6—C7—H7	120.2	C27—C26—H26A	110.7
C7—C8—C9	119.00 (16)	N2—C26—H26B	110.7
C7—C8—C13	120.79 (16)	C27—C26—H26B	110.7
C9—C8—C13	120.20 (15)	H26A—C26—H26B	108.8
N1—C9—C8	122.92 (16)	C28—C27—C26	113.54 (16)
N1—C9—C10	118.33 (15)	C28—C27—C12	115.08 (15)
C8—C9—C10	118.69 (15)	C26—C27—C12	103.16 (14)
C9—C10—C11	108.97 (14)	C28—C27—H27	108.2
C9—C10—C15	113.30 (14)	C26—C27—H27	108.2
C11—C10—C15	101.39 (14)	C12—C27—H27	108.2
C9—C10—H10	110.9	C33—C28—C29	117.68 (18)
C11—C10—H10	110.9	C33—C28—C27	122.91 (17)
C15—C10—H10	110.9	C29—C28—C27	119.39 (17)
C10—C11—C12	101.90 (13)	C28—C29—C30	121.9 (2)
C10—C11—H11A	111.4	C28—C29—H29	119.1
C12—C11—H11A	111.4	C30—C29—H29	119.1
C10—C11—H11B	111.4	C31—C30—C29	118.96 (19)
C12—C11—H11B	111.4	C31—C30—H30	120.5
H11A—C11—H11B	109.3	C29—C30—H30	120.5
C13—C12—C11	107.57 (14)	C30—C31—C32	120.8 (2)
C13—C12—C27	113.75 (15)	C30—C31—Cl1	119.69 (17)
C11—C12—C27	117.37 (15)	C32—C31—Cl1	119.56 (18)
C13—C12—C14	108.77 (13)	C31—C32—C33	119.4 (2)
C11—C12—C14	102.87 (13)	C31—C32—H32	120.3
C27—C12—C14	105.68 (13)	C33—C32—H32	120.3
O1—C13—C8	121.20 (16)	C28—C33—C32	121.3 (2)
O1—C13—C12	123.65 (16)	C28—C33—H33	119.4
C8—C13—C12	115.15 (14)	C32—C33—H33	119.4
N2—C14—C22	115.32 (13)	N2—C34—H34A	109.5
N2—C14—C12	102.19 (13)	N2—C34—H34B	109.5
C22—C14—C12	117.84 (14)	H34A—C34—H34B	109.5
N2—C14—C15	112.19 (14)	N2—C34—H34C	109.5
C22—C14—C15	103.50 (13)	H34A—C34—H34C	109.5
C12—C14—C15	105.66 (13)	H34B—C34—H34C	109.5
O2—C15—C16	112.06 (14)	C35A—O3—H3O	109.5
O2—C15—C10	107.96 (14)	C35Aⁱ—C35A—O3	121.1 (13)
C16—C15—C10	115.87 (14)	C35Aⁱ—C35A—H35A	107.1
O2—C15—C14	112.86 (14)	O3—C35A—H35A	107.1
C16—C15—C14	104.98 (13)	C35Aⁱ—C35A—H35B	107.1
C10—C15—C14	102.84 (13)	O3—C35A—H35B	107.1
C17—C16—C21	119.23 (18)	H35A—C35A—H35B	106.8
C17—C16—C15	132.34 (19)	C35Bⁱ—C35B—O3	118.6 (12)
C21—C16—C15	108.42 (15)	C35Bⁱ—C35B—H35C	107.7
C16—C17—C18	118.6 (2)	O3—C35B—H35C	107.7
C16—C17—H17	120.7	C35Bⁱ—C35B—H35D	107.7
C18—C17—H17	120.7	O3—C35B—H35D	107.7
C19—C18—C17	122.5 (2)	H35C—C35B—H35D	107.1

C9—N1—C1—C6	−2.3 (3)	N2—C14—C15—C16	114.11 (14)
C9—N1—C1—C2	176.14 (17)	C22—C14—C15—C16	−10.84 (16)
N1—C1—C2—C3	−178.35 (19)	C12—C14—C15—C16	−135.32 (13)
C6—C1—C2—C3	0.1 (3)	N2—C14—C15—C10	−124.27 (14)
C1—C2—C3—C4	−1.4 (4)	C22—C14—C15—C10	110.77 (14)
C2—C3—C4—C5	0.0 (3)	C12—C14—C15—C10	−13.71 (17)
C3—C4—C5—C6	2.6 (3)	O2—C15—C16—C17	−50.2 (3)
N1—C1—C6—C7	3.5 (3)	C10—C15—C16—C17	74.3 (2)
C2—C1—C6—C7	−174.87 (17)	C14—C15—C16—C17	−173.05 (19)
N1—C1—C6—C5	−179.23 (16)	O2—C15—C16—C21	131.07 (15)
C2—C1—C6—C5	2.4 (3)	C10—C15—C16—C21	−104.43 (16)
C4—C5—C6—C7	173.33 (18)	C14—C15—C16—C21	8.23 (17)
C4—C5—C6—C1	−3.7 (3)	C21—C16—C17—C18	−1.0 (3)
C1—C6—C7—C8	−0.8 (2)	C15—C16—C17—C18	−179.61 (18)
C5—C6—C7—C8	−177.90 (16)	C16—C17—C18—C19	2.0 (3)
C6—C7—C8—C9	−2.9 (2)	C17—C18—C19—C20	−0.3 (3)
C6—C7—C8—C13	175.65 (15)	C18—C19—C20—C21	−2.1 (3)
C1—N1—C9—C8	−1.7 (2)	C18—C19—C20—C25	177.5 (2)
C1—N1—C9—C10	−179.11 (15)	C17—C16—C21—C22	179.04 (16)
C7—C8—C9—N1	4.4 (2)	C15—C16—C21—C22	−2.0 (2)
C13—C8—C9—N1	−174.18 (15)	C17—C16—C21—C20	−1.5 (3)
C7—C8—C9—C10	−178.25 (15)	C15—C16—C21—C20	177.38 (15)
C13—C8—C9—C10	3.2 (2)	C25—C20—C21—C16	−176.57 (16)
N1—C9—C10—C11	142.05 (15)	C19—C20—C21—C16	3.0 (3)
C8—C9—C10—C11	−35.4 (2)	C25—C20—C21—C22	2.8 (3)
N1—C9—C10—C15	−105.91 (17)	C19—C20—C21—C22	−177.60 (17)
C8—C9—C10—C15	76.61 (19)	C16—C21—C22—C23	176.50 (16)
C9—C10—C11—C12	68.81 (16)	C20—C21—C22—C23	−2.9 (3)
C15—C10—C11—C12	−50.91 (16)	C16—C21—C22—C14	−5.43 (19)
C10—C11—C12—C13	−73.10 (16)	C20—C21—C22—C14	175.16 (15)
C10—C11—C12—C27	157.13 (15)	N2—C14—C22—C23	64.8 (3)
C10—C11—C12—C14	41.64 (17)	C12—C14—C22—C23	−56.1 (3)
C7—C8—C13—O1	−5.8 (2)	C15—C14—C22—C23	−172.29 (19)
C9—C8—C13—O1	172.71 (16)	N2—C14—C22—C21	−112.90 (16)
C7—C8—C13—C12	174.08 (14)	C12—C14—C22—C21	126.16 (15)
C9—C8—C13—C12	−7.4 (2)	C15—C14—C22—C21	10.01 (17)
C11—C12—C13—O1	−137.17 (17)	C21—C22—C23—C24	0.5 (3)
C27—C12—C13—O1	−5.4 (2)	C14—C22—C23—C24	−176.98 (18)
C14—C12—C13—O1	112.08 (18)	C22—C23—C24—C25	1.9 (3)
C11—C12—C13—C8	42.91 (18)	C23—C24—C25—C20	−2.0 (3)
C27—C12—C13—C8	174.68 (13)	C21—C20—C25—C24	−0.3 (3)
C14—C12—C13—C8	−67.84 (17)	C19—C20—C25—C24	−179.9 (2)
C26—N2—C14—C22	−89.00 (17)	C34—N2—C26—C27	−169.53 (17)
C34—N2—C14—C22	36.0 (2)	C14—N2—C26—C27	−42.71 (19)
C26—N2—C14—C12	40.12 (17)	N2—C26—C27—C28	−99.30 (18)
C34—N2—C14—C12	165.16 (16)	N2—C26—C27—C12	25.9 (2)
C26—N2—C14—C15	152.85 (15)	C13—C12—C27—C28	−118.14 (16)
C34—N2—C14—C15	−82.11 (19)	C11—C12—C27—C28	8.7 (2)
C13—C12—C14—N2	−145.22 (14)	C14—C12—C27—C28	122.61 (16)
C11—C12—C14—N2	100.90 (15)	C13—C12—C27—C26	117.64 (17)
C27—C12—C14—N2	−22.73 (17)	C11—C12—C27—C26	−115.54 (18)
C13—C12—C14—C22	−17.71 (19)	C14—C12—C27—C26	−1.61 (19)
C11—C12—C14—C22	−131.58 (15)	C26—C27—C28—C33	36.1 (3)
C27—C12—C14—C22	104.78 (17)	C12—C27—C28—C33	−82.5 (2)
C13—C12—C14—C15	97.27 (15)	C26—C27—C28—C29	−142.47 (19)
C11—C12—C14—C15	−16.61 (17)	C12—C27—C28—C29	99.0 (2)
C27—C12—C14—C15	−140.24 (14)	C33—C28—C29—C30	0.3 (3)
C9—C10—C15—O2	163.29 (14)	C27—C28—C29—C30	178.93 (19)
C11—C10—C15—O2	−80.11 (16)	C28—C29—C30—C31	0.6 (3)
C9—C10—C15—C16	36.7 (2)	C29—C30—C31—C32	−0.7 (4)
C11—C10—C15—C16	153.30 (15)	C29—C30—C31—Cl1	179.10 (17)
C9—C10—C15—C14	−77.19 (17)	C30—C31—C32—C33	−0.3 (4)
C11—C10—C15—C14	39.40 (16)	Cl1—C31—C32—C33	179.97 (19)
N2—C14—C15—O2	−8.21 (19)	C29—C28—C33—C32	−1.3 (3)
C22—C14—C15—O2	−133.17 (15)	C27—C28—C33—C32	−179.8 (2)
C12—C14—C15—O2	102.35 (16)	C31—C32—C33—C28	1.3 (4)

Symmetry code: (i) −x, −y+1, −z+1.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2O···N2	0.87 (3)	2.20 (3)	2.695 (2)	116 (2)
O3—H3O···N1	0.82	2.28	2.984 (4)	145
O2—H2O···O3ⁱⁱ	0.87 (3)	2.26 (3)	3.021 (5)	146 (2)
C33—H33···O3ⁱⁱ	0.93	2.53	3.408 (6)	157

Symmetry code: (ii) −x+1, −y+1, −z+1.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2O···N2	0.87 (3)	2.20 (3)	2.695 (2)	116 (2)
O3—H3O···N1	0.82	2.28	2.984 (4)	145
O2—H2O···O3ⁱ	0.87 (3)	2.26 (3)	3.021 (5)	146 (2)
C33—H33···O3ⁱ	0.93	2.53	3.408 (6)	157

Symmetry code: (i) −x+1, −y+1, −z+1.

Experimental details

Crystal data
Chemical formula	C₃₄H₂₅ClN₂O₂·0.5CH₄O
M_r	544.53
Crystal system, space group	Triclinic, P1
Temperature (K)	293
a, b, c (Å)	10.3848 (3), 10.4306 (3), 14.4513 (4)
α, β, γ (°)	69.394 (1), 72.388 (1), 70.871 (1)
V (Å³)	1352.92 (7)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.18
Crystal size (mm)	0.22 × 0.16 × 0.12

Data collection
Diffractometer	Bruker SMART APEXII area-detector
Absorption correction	Multi-scan (SADABS; Bruker, 2008)
T_min, T_max	0.966, 0.978
No. of measured, independent and observed [I > 2σ(I)] reflections	20173, 5563, 4425
R_int	0.019
(sin θ/λ)_max (Å⁻¹)	0.629

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.052, 0.178, 1.05
No. of reflections	5563
No. of parameters	386
No. of restraints	3
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.66, −0.44

Computer programs: APEX2 (Bruker, 2008), SAINT (Bruker, 2008), SHELXS97 (Sheldrick, 2008), SHELXL2014 (Sheldrick, 2015) and PLATON (Spek, 2009).

Acknowledgements

The authors thank the TBI X-ray facility, CAS in Crystallography and Biophysics, University of Madras, India, for the data collection.

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