(2Z,3E)-2-{[1-(4-Chloro­benz­yl)-1H-indol-3-yl]methyl­idene}quinuclidin-3-one oxime

Penthala, N.R.; Reddy, T.R.Y.; Parkin, S.; Crooks, P.A.

doi:10.1107/S160053681100612X

organic compounds

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ISSN: 2056-9890

Volume 67| Part 3| March 2011| Page o735

doi:10.1107/S160053681100612X

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(2Z,3E)-2-{[1-(4-Chlorobenzyl)-1H-indol-3-yl]methylidene}quinuclidin-3-one oxime

Narsimha Reddy Penthala,^a Thirupathi Reddy Yerram Reddy,^a Sean Parkin ^b and Peter A. Crooks ^a ^*

^aDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA, and ^bDepartment of Chemistry, University of Kentucky, Lexington, KY 40506, USA
^*Correspondence e-mail: pcrooks@uky.edu

(Received 7 December 2010; accepted 17 February 2011; online 26 February 2011)

In the title compound, C₂₃H₂₂ClN₃O, the benzene ring of the 4-chorobenzyl group makes a dihedral angle of 78.56 (6)° with the best plane of the indole ring. The double bond connecting the azabicyclic and indole groups adopts a Z geometry. The geometry adopted by the C=N bond with respect to the N—OH bond is trans. The absolute configuration of the compound was determined from refinement of the Flack parameter.

Related literature

For 2-indol-3-yl-methylenequinuclidin-3-ols and NADPH oxidase activity, see: Sekhar et al. (2003 ) and for novel substituted (Z)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-one and (Z)-(±)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-ol derivatives as potent thermal sensitizing agents, see: Sonar et al. (2007 ). For di- and triindolylmethanes: molecular structures, see: Mason et al. (2003 ) and for structures of 1H-indole-3-ethylene-3′-methoxysalicylaldimine and 3-[3′-azapentyl-3′-en-4′-(2′′-hydroxyphenyl)]indole, see: Zarza et al. (1988 ). For the radio-sensitization activity associated with N-benzylindolyl-1-azabicyclo[2.2.2]octan-3-ones, see: Sonar et al. (2003 ).

Experimental

Crystal data

C₂₃H₂₂ClN₃O
M_r = 391.89
Orthorhombic, P 2₁ 2₁ 2₁
a = 5.8382 (1) Å
b = 10.7005 (2) Å
c = 30.9451 (6) Å
V = 1933.19 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.22 mm⁻¹
T = 90 K
0.40 × 0.12 × 0.08 mm

Data collection

Nonius KappaCCD diffractometer
Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997 ) T_min = 0.918, T_max = 0.983
37270 measured reflections
4433 independent reflections
3150 reflections with I > 2σ(I)
R_int = 0.103

Refinement

R[F² > 2σ(F²)] = 0.049
wR(F²) = 0.137
S = 1.06
4433 reflections
254 parameters
H-atom parameters constrained
Δρ_max = 0.40 e Å⁻³
Δρ_min = −0.24 e Å⁻³
Absolute structure: Flack (1983 ), 1853 Friedel pairs
Flack parameter: −0.03 (4)

Data collection: COLLECT (Nonius, 1998 ); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO-SMN (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL97 and local procedures.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053681100612X/fj2375sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S160053681100612X/fj2375Isup2.hkl

checkCIF report

Comment top

In view of the radio-sensitization activity associated with N-benzylindolyl-1-azabicyclo[2.2.2]octan-3-ones (Sonar et al., 2007), we have undertaken the synthesis and structural analysis of a series of (2Z,3E)-2-((1-benzyl-1H-indol-3-yl)methylene) quinuclidin-3-one oximes. Systematic structural modification of the active molecule (Z)-2-(1-benzyl-1H-indol-3-ylmethylene)1- azabicyclo[2.2.2]octan-3-ol, was carried out, and the title compound was synthesized as its structural analogue. The X-ray analysis of the title compound was carried out to confirm the double-bond geometry of the molecule, and to determine the molecular conformation in the crystal structure.

X-ray crystallography confirmed the molecular structure and atom connectivity for title compound, as illustrated in Fig. 1. The indole ring is planar, with bond distances and angles comparable with those previously reported for other indole derivatives (Mason et al.., 2003; Zarza et al.., 1988). The benzene ring of the benzyl group linked to the N1 position of the indole ring is slightly twisted, making a dihedral angle of 78.56 (6)° with the plane of the indole ring system.

The title compound is the Z isomer, with the C10—C11 bond in a trans disposition with respect to the C8—C9 bond. The double bond has a nearly planar arrangement, since the r.m.s. deviation from the best plane passing through atoms N2/C10/ C11/C9/C8 is 0.0143 (15) Å. The azabicyclic system presents very small distortions around atoms N2, C14, C13, C12, C16 and C11. The value of the C1=C8—C9=C10 torsion angle -13.87° indicates the deviation of the indole ring from the plane of the double bond connected to the azabicyclic ring.

Related literature top

For 2-indol-3-yl-methylenequinuclidin-3-ols and NADPH oxidase activity, see: Sekhar et al. (2003) and for novel substituted (Z)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-one and (Z)-(±)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-ol derivatives as potent thermal sensitizing agents, see: Sonar et al. (2007). Di- and triindolylmethanes: molecular structures have been described by Mason et al. (2003); structures of 1H-indole-3-ethylene-3'-methoxysalicylaldimine and 3-[3'-azapentyl-3'-en-4'-(2''-hydroxyphenyl)]indole were described by Zarza, et al. (1988). For the radio-sensitization activity associated with N-benzylindolyl-1-azabicyclo[2.2.2]octan-3-ones, see: Sonar et al. (2003).

Experimental top

Compound 2-((1-(4-chlorobenzyl)-1H-indol-3-yl)methylene) quinuclidin-3-one was prepared by aldol condensation of 1-(4-chlorobenzyl-indole-3-carboxaldehyde with 1-azabicyclo[2.2.2]octan- 3-one to afford (Z)-2-(1-(4-chlorobenzyl-1H-indol-3-yl methylene)-1-azabicyclo[2.2.2]octan-3-one, as a single geometric isomer, according to the previously reported procedure of Sonar et al. (2003). A mixture (Z)-2-(1-(4-chlorobenzyl-1H-indol-3-yl methylene)1-azabicyclo[2.2.2]octan-3-one (0.5 g, 1.32 mmol), hydroxylamine hydrocloride (0.18 g, 2.65 mmol) and sodium acetate trihydrate (0.36 g, 2.65 mmol) was stirred in methanol (25 ml) under reflux for 8 hrs. The reaction mixture was cooled to room temperature, diluted with water (15 ml), and the light yellow solid that separated was collected by filtration, washed with water and dried, to afford the the crude product. Crystallization from methanol gave a colorless crystalline product of (2Z,3E)-2- ((1-(4-chlorobenzyl)-1H-indol-3-yl)methylene) quinuclidin-3-one oxime that was suitable for X-ray analysis. ¹H NMR (CDCl₃): δ 1.76–1.79 (m, 4H), 2.91–3.09 (m, 4H), 3.67–3.69 (m, 1H), 5.34 (s, 2H), 7.01–7.04 (d, 2H), 7.10 (s, 1H), 7.14–7.25 (m, 5H), 7.30 (bs, 1H), 7.79–7.83 (d, 1H), 8.21 (s, 1H) p.p.m.; ¹³C NMR (DMSO d₆): δ 24.46, 25.87, 47.77, 50.06, 109.92, 110.45, 111.47, 119.34, 120.34, 122.39, 128.05, 128.63, 129.09, 131.27, 133.54, 135.80, 135.98, 138.23, 161.31 p.p.m..

Computing details top

Data collection: COLLECT (Nonius, 1998); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO-SMN (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and local procedures.

Figures top

Fig. 1. A view of the molecule with the atom numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.

(2Z,3E)-2-{[1-(4-Chlorobenzyl)-1H-indol-3- yl]methylidene}quinuclidin-3-one oxime top

Crystal data top

C₂₃H₂₂ClN₃O	F(000) = 824
M_r = 391.89	D_x = 1.346 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 2610 reflections
a = 5.8382 (1) Å	θ = 1.0–27.5°
b = 10.7005 (2) Å	µ = 0.22 mm⁻¹
c = 30.9451 (6) Å	T = 90 K
V = 1933.19 (6) Å³	Plate, colourless
Z = 4	0.40 × 0.12 × 0.08 mm

Data collection top

Nonius KappaCCD diffractometer	4433 independent reflections
Radiation source: fine-focus sealed tube	3150 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.103
Detector resolution: 9.1 pixels mm^-1	θ_max = 27.5°, θ_min = 1.3°
ω scans at fixed χ = 55°	h = −7→7
Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997)	k = −13→13
T_min = 0.918, T_max = 0.983	l = −39→40
37270 measured reflections

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.049	H-atom parameters constrained
wR(F²) = 0.137	w = 1/[σ²(F_o²) + (0.0788P)²] where P = (F_o² + 2F_c²)/3
S = 1.06	(Δ/σ)_max < 0.001
4433 reflections	Δρ_max = 0.40 e Å⁻³
254 parameters	Δρ_min = −0.24 e Å⁻³
0 restraints	Absolute structure: Flack (1983), 1853 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.03 (4)

Crystal data top

C₂₃H₂₂ClN₃O	V = 1933.19 (6) Å³
M_r = 391.89	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 5.8382 (1) Å	µ = 0.22 mm⁻¹
b = 10.7005 (2) Å	T = 90 K
c = 30.9451 (6) Å	0.40 × 0.12 × 0.08 mm

Data collection top

Nonius KappaCCD diffractometer	4433 independent reflections
Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997)	3150 reflections with I > 2σ(I)
T_min = 0.918, T_max = 0.983	R_int = 0.103
37270 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.049	H-atom parameters constrained
wR(F²) = 0.137	Δρ_max = 0.40 e Å⁻³
S = 1.06	Δρ_min = −0.24 e Å⁻³
4433 reflections	Absolute structure: Flack (1983), 1853 Friedel pairs
254 parameters	Absolute structure parameter: −0.03 (4)
0 restraints

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.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > 2σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	U_iso*/U_eq
N1	0.1498 (4)	0.0866 (2)	0.89083 (7)	0.0245 (5)
N2	0.0660 (4)	0.1260 (2)	0.75130 (7)	0.0265 (5)
N3	0.3789 (4)	0.4000 (2)	0.71465 (7)	0.0311 (6)
O1	0.3831 (4)	0.45515 (18)	0.67293 (6)	0.0327 (5)
H1O	0.4731	0.5164	0.6730	0.049*
Cl1	0.28052 (15)	−0.51575 (6)	0.95786 (2)	0.0408 (2)
C1	0.1254 (5)	0.1143 (3)	0.84757 (8)	0.0263 (6)
H1	0.0091	0.0816	0.8293	0.032*
C2	0.3379 (5)	0.1501 (2)	0.90706 (9)	0.0257 (6)
C3	0.4304 (5)	0.1521 (2)	0.94836 (9)	0.0313 (7)
H3	0.3656	0.1040	0.9711	0.038*
C4	0.6191 (5)	0.2263 (3)	0.95518 (10)	0.0338 (7)
H4	0.6823	0.2314	0.9834	0.041*
C5	0.7198 (5)	0.2941 (2)	0.92199 (9)	0.0357 (7)
H5	0.8529	0.3425	0.9276	0.043*
C6	0.6283 (5)	0.2917 (2)	0.88076 (9)	0.0303 (7)
H6	0.6975	0.3385	0.8582	0.036*
C7	0.4340 (5)	0.2203 (2)	0.87271 (9)	0.0252 (6)
C8	0.2938 (5)	0.1964 (2)	0.83457 (8)	0.0241 (6)
C9	0.3253 (5)	0.2570 (2)	0.79299 (9)	0.0249 (6)
H9	0.4310	0.3245	0.7925	0.030*
C10	0.2250 (5)	0.2300 (2)	0.75544 (8)	0.0232 (6)
C11	0.2554 (5)	0.2987 (2)	0.71447 (8)	0.0254 (6)
C12	0.1228 (5)	0.2401 (3)	0.67821 (9)	0.0307 (7)
H12	0.1483	0.2857	0.6504	0.037*
C13	−0.1316 (5)	0.2419 (3)	0.69126 (10)	0.0371 (7)
H13A	−0.2244	0.1972	0.6694	0.044*
H13B	−0.1872	0.3292	0.6931	0.044*
C14	−0.1551 (5)	0.1767 (3)	0.73590 (9)	0.0306 (7)
H14A	−0.2140	0.2376	0.7573	0.037*
H14B	−0.2677	0.1078	0.7336	0.037*
C15	0.1538 (5)	0.0380 (2)	0.71842 (8)	0.0297 (7)
H15A	0.0415	−0.0303	0.7143	0.036*
H15B	0.2984	0.0004	0.7289	0.036*
C16	0.1976 (6)	0.1027 (3)	0.67474 (9)	0.0355 (7)
H16A	0.3624	0.0980	0.6674	0.043*
H16B	0.1096	0.0603	0.6517	0.043*
C17	−0.0065 (5)	0.0109 (2)	0.91598 (9)	0.0283 (6)
H17A	−0.1531	0.0046	0.9001	0.034*
H17B	−0.0380	0.0546	0.9435	0.034*
C18	0.0755 (5)	−0.1200 (3)	0.92624 (8)	0.0256 (6)
C19	−0.0692 (5)	−0.1968 (3)	0.95003 (8)	0.0289 (6)
H19	−0.2120	−0.1649	0.9597	0.035*
C20	−0.0099 (5)	−0.3190 (2)	0.95994 (9)	0.0295 (6)
H20	−0.1105	−0.3710	0.9760	0.035*
C21	0.1993 (5)	−0.3631 (2)	0.94579 (9)	0.0291 (7)
C22	0.3478 (5)	−0.2890 (2)	0.92239 (8)	0.0292 (7)
H22	0.4916	−0.3209	0.9131	0.035*
C23	0.2838 (5)	−0.1665 (2)	0.91249 (8)	0.0263 (6)
H23	0.3841	−0.1148	0.8962	0.032*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0254 (13)	0.0248 (12)	0.0232 (12)	0.0017 (10)	0.0011 (10)	−0.0014 (9)
N2	0.0248 (13)	0.0252 (12)	0.0297 (13)	−0.0052 (11)	0.0008 (11)	0.0003 (10)
N3	0.0348 (15)	0.0266 (12)	0.0321 (13)	0.0075 (11)	0.0085 (12)	0.0067 (10)
O1	0.0341 (13)	0.0300 (11)	0.0340 (11)	−0.0025 (9)	0.0030 (9)	0.0037 (8)
Cl1	0.0491 (5)	0.0268 (4)	0.0464 (4)	0.0042 (4)	0.0006 (4)	0.0036 (3)
C1	0.0252 (15)	0.0261 (13)	0.0277 (15)	0.0036 (12)	−0.0044 (12)	−0.0025 (12)
C2	0.0287 (17)	0.0232 (14)	0.0252 (14)	0.0076 (12)	−0.0020 (12)	−0.0046 (11)
C3	0.0337 (17)	0.0270 (15)	0.0332 (17)	0.0081 (13)	−0.0022 (14)	−0.0056 (12)
C4	0.0417 (19)	0.0278 (14)	0.0318 (16)	0.0108 (14)	−0.0103 (15)	−0.0074 (13)
C5	0.0348 (18)	0.0264 (14)	0.0460 (18)	0.0022 (14)	−0.0096 (15)	−0.0120 (13)
C6	0.0320 (17)	0.0222 (14)	0.0367 (17)	0.0010 (13)	−0.0031 (14)	−0.0031 (12)
C7	0.0217 (15)	0.0228 (14)	0.0311 (15)	0.0027 (12)	0.0008 (12)	−0.0048 (12)
C8	0.0264 (15)	0.0173 (12)	0.0287 (14)	0.0014 (12)	0.0010 (12)	−0.0016 (10)
C9	0.0198 (14)	0.0208 (12)	0.0342 (15)	0.0015 (12)	0.0011 (12)	0.0005 (11)
C10	0.0175 (14)	0.0199 (12)	0.0323 (15)	−0.0013 (12)	0.0050 (12)	0.0021 (11)
C11	0.0221 (15)	0.0217 (13)	0.0325 (15)	0.0015 (12)	0.0029 (13)	0.0031 (11)
C12	0.0309 (17)	0.0337 (16)	0.0275 (16)	−0.0038 (14)	0.0004 (13)	0.0065 (12)
C13	0.0264 (17)	0.0386 (17)	0.0462 (18)	−0.0001 (14)	−0.0041 (15)	0.0116 (14)
C14	0.0216 (16)	0.0336 (15)	0.0368 (17)	−0.0003 (13)	−0.0009 (13)	0.0009 (13)
C15	0.0326 (17)	0.0222 (13)	0.0342 (16)	−0.0013 (13)	−0.0030 (13)	−0.0045 (12)
C16	0.0412 (19)	0.0346 (16)	0.0306 (16)	−0.0054 (15)	0.0029 (14)	−0.0057 (13)
C17	0.0265 (16)	0.0286 (15)	0.0298 (15)	0.0020 (13)	0.0035 (12)	0.0011 (12)
C18	0.0261 (15)	0.0285 (14)	0.0224 (14)	0.0010 (13)	−0.0023 (12)	−0.0018 (11)
C19	0.0289 (16)	0.0324 (15)	0.0254 (15)	0.0032 (13)	0.0012 (13)	−0.0002 (12)
C20	0.0311 (17)	0.0284 (14)	0.0288 (15)	−0.0034 (13)	0.0066 (13)	0.0033 (13)
C21	0.0377 (18)	0.0229 (13)	0.0268 (14)	0.0035 (13)	−0.0051 (13)	−0.0020 (11)
C22	0.0308 (17)	0.0297 (15)	0.0270 (15)	0.0041 (13)	−0.0003 (13)	−0.0038 (12)
C23	0.0255 (16)	0.0289 (14)	0.0247 (14)	−0.0023 (13)	0.0022 (13)	−0.0009 (11)

Geometric parameters (Å, º) top

N1—C1	1.379 (3)	C11—C12	1.500 (4)
N1—C2	1.385 (4)	C12—C16	1.538 (4)
N1—C17	1.448 (3)	C12—C13	1.539 (4)
N2—C10	1.455 (3)	C12—H12	1.0000
N2—C15	1.479 (3)	C13—C14	1.554 (4)
N2—C14	1.479 (4)	C13—H13A	0.9900
N3—C11	1.302 (4)	C13—H13B	0.9900
N3—O1	1.420 (3)	C14—H14A	0.9900
O1—H1O	0.8400	C14—H14B	0.9900
Cl1—C21	1.741 (3)	C15—C16	1.540 (4)
C1—C8	1.378 (4)	C15—H15A	0.9900
C1—H1	0.9500	C15—H15B	0.9900
C2—C3	1.387 (4)	C16—H16A	0.9900
C2—C7	1.418 (4)	C16—H16B	0.9900
C3—C4	1.374 (4)	C17—C18	1.514 (4)
C3—H3	0.9500	C17—H17A	0.9900
C4—C5	1.388 (4)	C17—H17B	0.9900
C4—H4	0.9500	C18—C23	1.381 (4)
C5—C6	1.383 (4)	C18—C19	1.389 (4)
C5—H5	0.9500	C19—C20	1.387 (4)
C6—C7	1.390 (4)	C19—H19	0.9500
C6—H6	0.9500	C20—C21	1.380 (4)
C7—C8	1.459 (4)	C20—H20	0.9500
C8—C9	1.453 (4)	C21—C22	1.381 (4)
C9—C10	1.333 (3)	C22—C23	1.397 (4)
C9—H9	0.9500	C22—H22	0.9500
C10—C11	1.476 (3)	C23—H23	0.9500

C1—N1—C2	109.2 (2)	C12—C13—H13A	110.1
C1—N1—C17	125.3 (2)	C14—C13—H13A	110.1
C2—N1—C17	125.4 (2)	C12—C13—H13B	110.1
C10—N2—C15	109.1 (2)	C14—C13—H13B	110.1
C10—N2—C14	107.7 (2)	H13A—C13—H13B	108.4
C15—N2—C14	108.3 (2)	N2—C14—C13	112.0 (2)
C11—N3—O1	110.6 (2)	N2—C14—H14A	109.2
N3—O1—H1O	109.5	C13—C14—H14A	109.2
C8—C1—N1	110.3 (2)	N2—C14—H14B	109.2
C8—C1—H1	124.9	C13—C14—H14B	109.2
N1—C1—H1	124.9	H14A—C14—H14B	107.9
N1—C2—C3	130.6 (3)	N2—C15—C16	112.0 (2)
N1—C2—C7	107.6 (2)	N2—C15—H15A	109.2
C3—C2—C7	121.9 (3)	C16—C15—H15A	109.2
C4—C3—C2	117.6 (3)	N2—C15—H15B	109.2
C4—C3—H3	121.2	C16—C15—H15B	109.2
C2—C3—H3	121.2	H15A—C15—H15B	107.9
C3—C4—C5	121.8 (3)	C12—C16—C15	108.8 (2)
C3—C4—H4	119.1	C12—C16—H16A	109.9
C5—C4—H4	119.1	C15—C16—H16A	109.9
C6—C5—C4	120.6 (3)	C12—C16—H16B	109.9
C6—C5—H5	119.7	C15—C16—H16B	109.9
C4—C5—H5	119.7	H16A—C16—H16B	108.3
C5—C6—C7	119.4 (3)	N1—C17—C18	115.6 (2)
C5—C6—H6	120.3	N1—C17—H17A	108.4
C7—C6—H6	120.3	C18—C17—H17A	108.4
C6—C7—C2	118.7 (3)	N1—C17—H17B	108.4
C6—C7—C8	134.4 (3)	C18—C17—H17B	108.4
C2—C7—C8	106.9 (2)	H17A—C17—H17B	107.4
C1—C8—C9	129.3 (3)	C23—C18—C19	119.0 (3)
C1—C8—C7	106.0 (2)	C23—C18—C17	123.2 (3)
C9—C8—C7	124.5 (2)	C19—C18—C17	117.8 (3)
C10—C9—C8	128.3 (3)	C20—C19—C18	121.5 (3)
C10—C9—H9	115.9	C20—C19—H19	119.2
C8—C9—H9	115.9	C18—C19—H19	119.2
C9—C10—N2	121.5 (2)	C21—C20—C19	118.2 (3)
C9—C10—C11	126.0 (2)	C21—C20—H20	120.9
N2—C10—C11	112.5 (2)	C19—C20—H20	120.9
N3—C11—C10	118.5 (2)	C20—C21—C22	121.7 (3)
N3—C11—C12	129.5 (2)	C20—C21—Cl1	119.6 (2)
C10—C11—C12	111.9 (2)	C22—C21—Cl1	118.7 (2)
C11—C12—C16	107.8 (2)	C21—C22—C23	119.0 (3)
C11—C12—C13	107.3 (2)	C21—C22—H22	120.5
C16—C12—C13	107.7 (3)	C23—C22—H22	120.5
C11—C12—H12	111.3	C18—C23—C22	120.4 (3)
C16—C12—H12	111.3	C18—C23—H23	119.8
C13—C12—H12	111.3	C22—C23—H23	119.8
C12—C13—C14	108.2 (2)

C2—N1—C1—C8	−0.5 (3)	C9—C10—C11—N3	−4.8 (4)
C17—N1—C1—C8	175.3 (2)	N2—C10—C11—N3	174.5 (2)
C1—N1—C2—C3	−180.0 (3)	C9—C10—C11—C12	178.1 (3)
C17—N1—C2—C3	4.3 (4)	N2—C10—C11—C12	−2.7 (3)
C1—N1—C2—C7	0.2 (3)	N3—C11—C12—C16	127.3 (3)
C17—N1—C2—C7	−175.5 (2)	C10—C11—C12—C16	−55.9 (3)
N1—C2—C3—C4	−179.1 (3)	N3—C11—C12—C13	−117.0 (3)
C7—C2—C3—C4	0.7 (4)	C10—C11—C12—C13	59.8 (3)
C2—C3—C4—C5	−2.1 (4)	C11—C12—C13—C14	−54.6 (3)
C3—C4—C5—C6	1.9 (4)	C16—C12—C13—C14	61.1 (3)
C4—C5—C6—C7	−0.2 (4)	C10—N2—C14—C13	60.5 (3)
C5—C6—C7—C2	−1.1 (4)	C15—N2—C14—C13	−57.4 (3)
C5—C6—C7—C8	179.7 (3)	C12—C13—C14—N2	−3.5 (4)
N1—C2—C7—C6	−179.3 (2)	C10—N2—C15—C16	−55.6 (3)
C3—C2—C7—C6	0.9 (4)	C14—N2—C15—C16	61.4 (3)
N1—C2—C7—C8	0.1 (3)	C11—C12—C16—C15	57.8 (3)
C3—C2—C7—C8	−179.7 (2)	C13—C12—C16—C15	−57.6 (3)
N1—C1—C8—C9	−175.4 (2)	N2—C15—C16—C12	−3.0 (3)
N1—C1—C8—C7	0.5 (3)	C1—N1—C17—C18	104.6 (3)
C6—C7—C8—C1	178.9 (3)	C2—N1—C17—C18	−80.3 (3)
C2—C7—C8—C1	−0.4 (3)	N1—C17—C18—C23	−0.6 (4)
C6—C7—C8—C9	−5.0 (5)	N1—C17—C18—C19	−179.5 (2)
C2—C7—C8—C9	175.8 (2)	C23—C18—C19—C20	−0.5 (4)
C1—C8—C9—C10	−13.9 (5)	C17—C18—C19—C20	178.4 (2)
C7—C8—C9—C10	170.9 (3)	C18—C19—C20—C21	0.5 (4)
C8—C9—C10—N2	−2.2 (4)	C19—C20—C21—C22	0.0 (4)
C8—C9—C10—C11	176.9 (3)	C19—C20—C21—Cl1	179.6 (2)
C15—N2—C10—C9	−121.0 (3)	C20—C21—C22—C23	−0.5 (4)
C14—N2—C10—C9	121.6 (3)	Cl1—C21—C22—C23	179.9 (2)
C15—N2—C10—C11	59.7 (3)	C19—C18—C23—C22	0.0 (4)
C14—N2—C10—C11	−57.7 (3)	C17—C18—C23—C22	−178.9 (3)
O1—N3—C11—C10	−178.2 (2)	C21—C22—C23—C18	0.5 (4)
O1—N3—C11—C12	−1.6 (4)

Experimental details

Crystal data
Chemical formula	C₂₃H₂₂ClN₃O
M_r	391.89
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	90
a, b, c (Å)	5.8382 (1), 10.7005 (2), 30.9451 (6)
V (Å³)	1933.19 (6)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.22
Crystal size (mm)	0.40 × 0.12 × 0.08

Data collection
Diffractometer	Nonius KappaCCD diffractometer
Absorption correction	Multi-scan (SCALEPACK; Otwinowski & Minor, 1997)
T_min, T_max	0.918, 0.983
No. of measured, independent and observed [I > 2σ(I)] reflections	37270, 4433, 3150
R_int	0.103
(sin θ/λ)_max (Å⁻¹)	0.649

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.049, 0.137, 1.06
No. of reflections	4433
No. of parameters	254
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.40, −0.24
Absolute structure	Flack (1983), 1853 Friedel pairs
Absolute structure parameter	−0.03 (4)

Computer programs: COLLECT (Nonius, 1998), SCALEPACK (Otwinowski & Minor, 1997), DENZO-SMN (Otwinowski & Minor, 1997), SHELXS97 (Sheldrick, 2008), XP in SHELXTL (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008) and local procedures.

Acknowledgements

We are grateful to the NCI/NIH for their financial support under grant No. CA 140409.

References

Flack, H. D. (1983). Acta Cryst. A39, 876–881. CrossRef CAS Web of Science IUCr Journals Google Scholar
Mason, M. R., Barnard, T. S., Segla, M. F., Xie, B. & Kirschbaum, K. (2003). J. Chem. Crystallogr. 33, 531–540. Web of Science CSD CrossRef CAS Google Scholar
Nonius (1998). COLLECT. Nonius BV, Delft, The Netherlands. Google Scholar
Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307–326. New York: Academic Press. Google Scholar
Sekhar, K. R., Crooks, P. A., Sonar, V. N., Friedman, D. B., Chan, J. Y., Meredith, M. J., Stames, J. H., Kelton, K. R., Summar, S. R., Sasi, S. & Freeman, M. L. (2003). Cancer Res. 63, 5636–5645. Web of Science PubMed CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sonar, V. N., Parkin, S. & Crooks, P. A. (2003). Acta Cryst. E59, o1478–o1480. Web of Science CSD CrossRef IUCr Journals Google Scholar
Sonar, V. N., Reddy, Y. T., Sekhar, K. R., Sowmya, S., Freeman, M. L. & Crooks, P. A. (2007). Bioorg. Med. Chem. Lett. 17, 6821–6824. Web of Science CrossRef PubMed CAS Google Scholar
Zarza, P. M., Gill, P., Díaz González, M. C., Martin Reyes, M. G., Arrieta, J. M., Nastopoulos, V., Germain, G. & Debaerdemaeker, T. (1988). Acta Cryst. C44, 678–681. CSD CrossRef CAS Web of Science IUCr Journals Google Scholar

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