rac-N-Benzyl­isatincreatinine (unknown solvate)

Penthala, N.R.; Crooks, P.A.

doi:10.1107/S1600536813000378

organic compounds

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ISSN: 2056-9890

Volume 69| Part 2| February 2013| Pages o290-o291

doi:10.1107/S1600536813000378

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rac-N-Benzylisatincreatinine (unknown solvate)

Narsimha Reddy Penthala ^a and Peter A. Crooks ^a ^*

^aDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
^*Correspondence e-mail: pacrooks@uams.edu

(Received 11 December 2012; accepted 4 January 2013; online 26 January 2013)

The title compound, C₁₉H₁₈N₄O₃ [systematic name: (RS)-1-benzyl-3-hydroxy-3-(2-imino-3-methyl-5-oxoimidazolidin-4-yl)-2,3-dihydro-1H-indol-2-one], was prepared as a racemate (RR and SS) by the aldol condensation of N-benzylisatin with creatinine in the presence of sodium acetate in acetic acid. The r.m.s. deviation of the isatin ring system is 0.033 Å. The benzyl group is disordered over two orientations, with refined occupancies of 0.847 (7) and 0.153 (7). The dihedral angles between the isatin ring system and the benzene ring (major disorder component) and the imidazole ring are 82.82 (7) and 51.31 (3)°, respectively, In the crystal, molecules are linked into (001) sheets by N—H⋯O and O—H⋯N hydrogen bonds, which incorporate R₂²(9) ring motifs. The crystal was grown from mixed solvents (ethanol, methanol and possibly also ethyl acetate). These solvents are disordered in the crystal and the resulting electron density was found to be uninterpretable. The solvent contribution to the scattering was removed with the SQUEEZE routine in PLATON [Spek (2009 ). Acta Cryst. D65, 148–155]. The formula mass and density do not take account of the solvent.

Related literature

For details on the development of isatin derivatives as anticancer agents, see: Penthala et al. (2010a ,b ). For similar structures, see: Tang et al. (2009 ); Penthala et al. (2009a ,b ).

Experimental

Crystal data

C₁₉H₁₈N₄O₃
M_r = 350.37
Orthorhombic, P b c a
a = 13.4466 (2) Å
b = 10.6921 (2) Å
c = 27.2057 (5) Å
V = 3911.43 (12) Å³
Z = 8
Cu Kα radiation
μ = 0.68 mm⁻¹
T = 90 K
0.12 × 0.10 × 0.04 mm

Data collection

Bruker X8 Proteum CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2006 ) T_min = 0.911, T_max = 0.973
55165 measured reflections
3602 independent reflections
3344 reflections with I > 2σ(I)
R_int = 0.043

Refinement

R[F² > 2σ(F²)] = 0.038
wR(F²) = 0.104
S = 1.04
3602 reflections
287 parameters
222 restraints
H-atom parameters constrained
Δρ_max = 0.28 e Å⁻³
Δρ_min = −0.30 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O9—H9⋯N12ⁱ	0.84	1.97	2.8065 (13)	175
N13—H13A⋯O11ⁱⁱ	0.88	2.24	2.9321 (13)	135
N13—H13B⋯O1ⁱⁱⁱ	0.88	1.97	2.8410 (14)	173
Symmetry codes: (i) $[-x+1, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]$ ; (ii) $[x+{\script{1\over 2}}, y, -z+{\script{3\over 2}}]$ ; (iii) $[-x+1, y+{\script{1\over 2}}, -z+{\script{3\over 2}}]$ .

Data collection: APEX2 (Bruker, 2006); cell refinement: SAINT (Bruker, 2006); data reduction: SAINT; 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: SHELX97.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536813000378/hb7013sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536813000378/hb7013Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536813000378/hb7013Isup3.cml

checkCIF report

Comment top

In continuation of our work on the development of anti-cancer agents (Penthala et al., 2010a,b), we have synthesized a series of new compounds containing isatin and creatinine moieties to screen for anticancer activity against a panel of 60 human cancer cell lines (Penthala et al., 2010a). The title compound was prepared by the aldol condensation of N-benzylindol-2,3-dione (N-benzylisatin) with 2-amino-1-methyl-1H-imidazol-4(5H)-one (creatinine) in the presence of sodium acetate in acetic acid. Earlier, we reported on the crystal structure of isatin creatinine analogs containing N-methyl and N-phenyl substituents (Penthala et al., 2009a,b). To obtain detailed information on the structural conformations of the molecules for analysis of structure-activity relationships (SAR), we determined the X-ray crystal structure of the title compound (Fig. 1). In the crystal, the benzyl group is disordered over two positions, with refined occupancies of 0.847 (7) and 0.153 (7). The isatin ring is almost planar, with r.m.s deviations from the mean plane = 0.0508 (11) Å, and with bond distances and angles comparable to those reported for other isatin derivatives (Tang et al., 2009). The benzene ring of the benzyl group makes a dihedral angle with the mean plane of the isatin ring of 82.82 (7)°. The title compound was isolated as a racemate (RR and SS). In the crystal, the molecules are linked into 2-D pleated-sheet networks in the ab plane by a series of intermolecular N—H—O and O—H—N hydrogen bonds. Within these sheets, the hydrogen bonds O9—H···N12, N13—H13A···O11 and N13—H13B···O1 create R²₂(9) ring motifs.

Related literature top

For details on the development of isatin derivatives as anticancer agents, see: Penthala et al. (2010a,b). For similar structures, see: Tang et al. (2009); Penthala et al. (2009a,b).

Experimental top

The title compound was prepared according to a previously reported procedure (Penthala et al., 2009a,b). Recrystallization from ethanol afforded the title compound as pale yellow plates. Spectroscopic data for rac-N-benzylisatincreatinine: ¹H NMR (DMSO-d₆): δ 3.17 (s, 3H, CH₃), 4.21 (s, 1H, CH), 4.74–4.91 (ABq, J= 16.2 Hz), 6.57 (s, 1H, OH), 6.64–6.67 (d, J= 8.1 HZ, 1H, –C₄H), 6.91–6.96 (t, J=7.5 Hz, 1H, –C₅H), 7.11–7.34 (m, 5H, –C₆H, –C₇H and Ar—H), 7.45–7.47 (d, J=7.2 Hz, 2H, Ar—H),7.56 (bs, 2H, NH₂); ¹³C NMR (DMSO-d₆): δ 32.67, 42.89, 69.52, 76.02, 108.99, 121.89, 123.72, 126.99, 127.14 (2 C) 127.43, 128.22 (2 C), 129.34, 136.01, 143.15, 171.96 (C=N), 174.42 (isatin C=O), 182.26 (creatinine C=O).

Computing details top

Data collection: APEX2 (Bruker, 2006); cell refinement: SAINT (Bruker, 2006); data reduction: SAINT (Bruker, 2006); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP (Sheldrick, 2008); software used to prepare material for publication: SHELX97 (Sheldrick, 2008).

Figures top

	Fig. 1. A view of (I). Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. Hydrogen bonding in the crystal structure of (I). Dashed lines represent hydrogen bonds.

1-Benzyl-3-hydroxy-3-(2-imino-3-methyl-5-oxoimidazolidin-4-yl)- 2,3-dihydro-1H-indol-2-one top

Crystal data top

C₁₉H₁₈N₄O₃	F(000) = 1472
M_r = 350.37	D_x = 1.190 Mg m⁻³
Orthorhombic, Pbca	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 9086 reflections
a = 13.4466 (2) Å	θ = 4.6–68.9°
b = 10.6921 (2) Å	µ = 0.68 mm⁻¹
c = 27.2057 (5) Å	T = 90 K
V = 3911.43 (12) Å³	Plate, pale yellow
Z = 8	0.12 × 0.10 × 0.04 mm

Data collection top

Bruker X8 Proteum CCD diffractometer	3602 independent reflections
Radiation source: fine-focus rotating anode	3344 reflections with I > 2σ(I)
Graded multilayer optics monochromator	R_int = 0.043
Detector resolution: 5.6 pixels mm^-1	θ_max = 68.7°, θ_min = 4.6°
ϕ and ω scans	h = −16→16
Absorption correction: multi-scan (SADABS; Bruker, 2006)	k = −12→12
T_min = 0.911, T_max = 0.973	l = −32→31
55165 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)] = 0.038	H-atom parameters constrained
wR(F²) = 0.104	w = 1/[σ²(F_o²) + (0.0555P)² + 1.5834P] where P = (F_o² + 2F_c²)/3
S = 1.04	(Δ/σ)_max = 0.001
3602 reflections	Δρ_max = 0.28 e Å⁻³
287 parameters	Δρ_min = −0.30 e Å⁻³
222 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.00043 (9)

Crystal data top

C₁₉H₁₈N₄O₃	V = 3911.43 (12) Å³
M_r = 350.37	Z = 8
Orthorhombic, Pbca	Cu Kα radiation
a = 13.4466 (2) Å	µ = 0.68 mm⁻¹
b = 10.6921 (2) Å	T = 90 K
c = 27.2057 (5) Å	0.12 × 0.10 × 0.04 mm

Data collection top

Bruker X8 Proteum CCD diffractometer	3602 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2006)	3344 reflections with I > 2σ(I)
T_min = 0.911, T_max = 0.973	R_int = 0.043
55165 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.038	222 restraints
wR(F²) = 0.104	H-atom parameters constrained
S = 1.04	Δρ_max = 0.28 e Å⁻³
3602 reflections	Δρ_min = −0.30 e Å⁻³
287 parameters

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	Occ. (<1)
O1	0.34991 (6)	0.33786 (8)	0.64888 (3)	0.0243 (2)
C1	0.41054 (9)	0.42315 (12)	0.65145 (4)	0.0212 (3)
N2	0.40105 (8)	0.53751 (10)	0.63017 (4)	0.0240 (2)
C3	0.48704 (9)	0.61071 (13)	0.63800 (4)	0.0252 (3)
C4	0.50442 (11)	0.73157 (14)	0.62246 (5)	0.0339 (3)
H4	0.4551	0.7781	0.6054	0.041*
C5	0.59772 (12)	0.78247 (14)	0.63292 (6)	0.0396 (4)
H5	0.6120	0.8657	0.6229	0.047*
C6	0.66974 (11)	0.71461 (14)	0.65753 (5)	0.0359 (3)
H6	0.7331	0.7508	0.6635	0.043*
C7	0.64986 (10)	0.59308 (13)	0.67374 (5)	0.0283 (3)
H7	0.6990	0.5464	0.6909	0.034*
C8	0.55730 (9)	0.54224 (12)	0.66432 (4)	0.0231 (3)
O9	0.56962 (6)	0.31592 (8)	0.66485 (3)	0.0238 (2)
H9	0.5498	0.2516	0.6796	0.036*
C9	0.51144 (9)	0.41884 (11)	0.67907 (4)	0.0202 (3)
C10	0.49128 (8)	0.41474 (11)	0.73572 (4)	0.0180 (3)
H10	0.4592	0.3339	0.7453	0.022*
O11	0.34262 (6)	0.54407 (8)	0.74190 (3)	0.0234 (2)
C11	0.42968 (9)	0.52621 (11)	0.75378 (4)	0.0188 (3)
N12	0.48658 (7)	0.60115 (9)	0.78275 (4)	0.0200 (2)
N13	0.65376 (7)	0.59593 (10)	0.80798 (4)	0.0228 (2)
H13A	0.7113	0.5567	0.8086	0.027*
H13B	0.6474	0.6691	0.8224	0.027*
C13	0.57697 (9)	0.54496 (11)	0.78532 (4)	0.0188 (3)
N14	0.58264 (7)	0.43382 (9)	0.76280 (3)	0.0185 (2)
C14	0.66413 (9)	0.34513 (12)	0.76781 (5)	0.0240 (3)
H14A	0.7141	0.3616	0.7424	0.036*
H14B	0.6386	0.2598	0.7640	0.036*
H14C	0.6945	0.3543	0.8004	0.036*
C15	0.31240 (10)	0.58041 (13)	0.60432 (5)	0.0262 (3)
H15A	0.2929	0.6630	0.6176	0.031*
H15B	0.2574	0.5214	0.6111	0.031*
C16	0.3251 (2)	0.5920 (3)	0.54852 (14)	0.0295 (5)	0.847 (7)
C17	0.2898 (2)	0.6974 (3)	0.52528 (8)	0.0565 (8)	0.847 (7)
H17	0.2631	0.7645	0.5440	0.068*	0.847 (7)
C18	0.2932 (3)	0.7056 (3)	0.47406 (8)	0.0724 (11)	0.847 (7)
H18	0.2687	0.7783	0.4580	0.087*	0.847 (7)
C19	0.3315 (2)	0.6099 (3)	0.44696 (10)	0.0573 (8)	0.847 (7)
H19	0.3337	0.6159	0.4121	0.069*	0.847 (7)
C20	0.3668 (3)	0.5051 (4)	0.46988 (15)	0.0397 (7)	0.847 (7)
H20	0.3936	0.4384	0.4509	0.048*	0.847 (7)
C21	0.3636 (3)	0.4957 (4)	0.52102 (15)	0.0313 (7)	0.847 (7)
H21	0.3881	0.4227	0.5368	0.038*	0.847 (7)
C16'	0.3153 (14)	0.5782 (19)	0.5524 (9)	0.0295 (5)	0.153 (7)
C17'	0.2496 (12)	0.6474 (16)	0.5261 (4)	0.054 (2)	0.153 (7)
H17'	0.2047	0.7002	0.5433	0.065*	0.153 (7)
C18'	0.2450 (13)	0.6442 (17)	0.4741 (4)	0.060 (2)	0.153 (7)
H18'	0.1982	0.6935	0.4565	0.072*	0.153 (7)
C19'	0.3107 (13)	0.5673 (16)	0.4500 (6)	0.054 (2)	0.153 (7)
H19'	0.3098	0.5632	0.4151	0.065*	0.153 (7)
C20'	0.3770 (18)	0.497 (2)	0.4756 (9)	0.042 (2)	0.153 (7)
H20'	0.4220	0.4438	0.4587	0.050*	0.153 (7)
C21'	0.3787 (17)	0.503 (2)	0.5264 (9)	0.033 (2)	0.153 (7)
H21'	0.4255	0.4533	0.5439	0.040*	0.153 (7)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0232 (4)	0.0268 (5)	0.0229 (4)	−0.0029 (4)	−0.0027 (3)	0.0017 (4)
C1	0.0227 (6)	0.0254 (6)	0.0154 (5)	−0.0006 (5)	0.0014 (4)	0.0013 (5)
N2	0.0241 (5)	0.0277 (6)	0.0202 (5)	−0.0014 (4)	−0.0022 (4)	0.0059 (4)
C3	0.0273 (6)	0.0290 (7)	0.0193 (6)	−0.0040 (5)	0.0020 (5)	0.0038 (5)
C4	0.0402 (8)	0.0320 (7)	0.0295 (7)	−0.0029 (6)	−0.0008 (6)	0.0104 (6)
C5	0.0493 (9)	0.0330 (8)	0.0364 (8)	−0.0140 (7)	0.0008 (7)	0.0116 (6)
C6	0.0373 (8)	0.0409 (8)	0.0295 (7)	−0.0162 (6)	0.0000 (6)	0.0063 (6)
C7	0.0280 (7)	0.0359 (7)	0.0210 (6)	−0.0067 (6)	0.0015 (5)	0.0040 (5)
C8	0.0257 (6)	0.0276 (6)	0.0161 (6)	−0.0036 (5)	0.0023 (5)	0.0027 (5)
O9	0.0236 (4)	0.0257 (5)	0.0221 (4)	0.0010 (3)	0.0040 (3)	−0.0004 (3)
C9	0.0199 (6)	0.0230 (6)	0.0178 (6)	−0.0008 (5)	0.0006 (4)	0.0010 (4)
C10	0.0172 (6)	0.0189 (6)	0.0178 (6)	−0.0008 (4)	−0.0004 (4)	0.0016 (4)
O11	0.0178 (4)	0.0229 (4)	0.0295 (5)	0.0006 (3)	−0.0024 (3)	0.0009 (3)
C11	0.0181 (6)	0.0203 (6)	0.0179 (5)	−0.0011 (4)	0.0011 (4)	0.0040 (4)
N12	0.0182 (5)	0.0209 (5)	0.0208 (5)	0.0006 (4)	−0.0003 (4)	−0.0001 (4)
N13	0.0191 (5)	0.0234 (5)	0.0258 (5)	0.0024 (4)	−0.0041 (4)	−0.0046 (4)
C13	0.0196 (6)	0.0223 (6)	0.0146 (5)	−0.0002 (5)	0.0007 (4)	0.0031 (4)
N14	0.0181 (5)	0.0187 (5)	0.0186 (5)	0.0014 (4)	−0.0015 (4)	0.0001 (4)
C14	0.0198 (6)	0.0215 (6)	0.0308 (6)	0.0028 (5)	−0.0044 (5)	−0.0001 (5)
C15	0.0248 (6)	0.0340 (7)	0.0199 (6)	0.0057 (5)	0.0006 (5)	0.0044 (5)
C16	0.0267 (10)	0.0427 (11)	0.0191 (9)	0.0057 (7)	0.0021 (7)	0.0076 (7)
C17	0.0808 (19)	0.0593 (16)	0.0294 (9)	0.0366 (14)	0.0088 (11)	0.0144 (10)
C18	0.106 (2)	0.078 (2)	0.0330 (10)	0.0440 (19)	0.0066 (13)	0.0227 (12)
C19	0.0693 (17)	0.083 (2)	0.0196 (9)	0.0199 (15)	0.0079 (10)	0.0136 (12)
C20	0.0358 (13)	0.0602 (14)	0.0230 (14)	0.0012 (11)	0.0021 (10)	−0.0050 (11)
C21	0.0316 (15)	0.0380 (11)	0.0243 (14)	−0.0012 (10)	−0.0027 (9)	−0.0008 (9)
C16'	0.0267 (10)	0.0427 (11)	0.0191 (9)	0.0057 (7)	0.0021 (7)	0.0076 (7)
C17'	0.068 (4)	0.064 (4)	0.030 (3)	0.024 (4)	0.005 (4)	0.012 (4)
C18'	0.081 (5)	0.072 (5)	0.026 (3)	0.031 (4)	−0.002 (4)	0.019 (4)
C19'	0.069 (4)	0.075 (5)	0.019 (4)	0.014 (4)	−0.001 (4)	0.008 (4)
C20'	0.044 (4)	0.059 (4)	0.023 (4)	0.005 (4)	0.000 (4)	0.001 (4)
C21'	0.029 (4)	0.051 (4)	0.020 (4)	−0.003 (4)	−0.001 (4)	0.004 (4)

Geometric parameters (Å, º) top

O1—C1	1.2253 (15)	C14—H14A	0.9800
C1—N2	1.3588 (16)	C14—H14B	0.9800
C1—C9	1.5516 (16)	C14—H14C	0.9800
N2—C3	1.4124 (17)	C15—C16'	1.41 (2)
N2—C15	1.4582 (16)	C15—C16	1.533 (4)
C3—C4	1.3796 (19)	C15—H15A	0.9900
C3—C8	1.3933 (18)	C15—H15B	0.9900
C4—C5	1.397 (2)	C16—C21	1.374 (3)
C4—H4	0.9500	C16—C17	1.377 (3)
C5—C6	1.383 (2)	C17—C18	1.397 (3)
C5—H5	0.9500	C17—H17	0.9500
C6—C7	1.398 (2)	C18—C19	1.362 (4)
C6—H6	0.9500	C18—H18	0.9500
C7—C8	1.3821 (18)	C19—C20	1.368 (4)
C7—H7	0.9500	C19—H19	0.9500
C8—C9	1.5107 (17)	C20—C21	1.396 (3)
O9—C9	1.4046 (15)	C20—H20	0.9500
O9—H9	0.8400	C21—H21	0.9500
C9—C10	1.5654 (16)	C16'—C17'	1.357 (16)
C10—N14	1.4468 (14)	C16'—C21'	1.368 (17)
C10—C11	1.5322 (16)	C17'—C18'	1.418 (13)
C10—H10	1.0000	C17'—H17'	0.9500
O11—C11	1.2295 (14)	C18'—C19'	1.373 (15)
C11—N12	1.3597 (16)	C18'—H18'	0.9500
N12—C13	1.3576 (15)	C19'—C20'	1.359 (16)
N13—C13	1.3204 (15)	C19'—H19'	0.9500
N13—H13A	0.8800	C20'—C21'	1.385 (17)
N13—H13B	0.8800	C20'—H20'	0.9500
C13—N14	1.3392 (16)	C21'—H21'	0.9500
N14—C14	1.4555 (15)

O1—C1—N2	125.66 (11)	N14—C14—H14B	109.5
O1—C1—C9	125.97 (11)	H14A—C14—H14B	109.5
N2—C1—C9	108.37 (10)	N14—C14—H14C	109.5
C1—N2—C3	110.95 (10)	H14A—C14—H14C	109.5
C1—N2—C15	124.43 (11)	H14B—C14—H14C	109.5
C3—N2—C15	124.59 (11)	C16'—C15—N2	117.0 (8)
C4—C3—C8	122.34 (12)	N2—C15—C16	114.35 (15)
C4—C3—N2	127.69 (12)	C16'—C15—H15A	112.9
C8—C3—N2	109.96 (11)	N2—C15—H15A	108.7
C3—C4—C5	117.03 (13)	C16—C15—H15A	108.7
C3—C4—H4	121.5	C16'—C15—H15B	101.4
C5—C4—H4	121.5	N2—C15—H15B	108.7
C6—C5—C4	121.55 (13)	C16—C15—H15B	108.7
C6—C5—H5	119.2	H15A—C15—H15B	107.6
C4—C5—H5	119.2	C21—C16—C17	119.6 (3)
C5—C6—C7	120.43 (13)	C21—C16—C15	121.4 (3)
C5—C6—H6	119.8	C17—C16—C15	118.9 (3)
C7—C6—H6	119.8	C16—C17—C18	119.8 (3)
C8—C7—C6	118.64 (13)	C16—C17—H17	120.1
C8—C7—H7	120.7	C18—C17—H17	120.1
C6—C7—H7	120.7	C19—C18—C17	120.4 (2)
C7—C8—C3	119.95 (12)	C19—C18—H18	119.8
C7—C8—C9	131.44 (12)	C17—C18—H18	119.8
C3—C8—C9	108.58 (11)	C18—C19—C20	120.0 (3)
C9—O9—H9	109.5	C18—C19—H19	120.0
O9—C9—C8	112.56 (10)	C20—C19—H19	120.0
O9—C9—C1	112.14 (10)	C19—C20—C21	120.2 (3)
C8—C9—C1	101.67 (9)	C19—C20—H20	119.9
O9—C9—C10	110.23 (9)	C21—C20—H20	119.9
C8—C9—C10	110.90 (9)	C16—C21—C20	120.0 (3)
C1—C9—C10	109.04 (9)	C16—C21—H21	120.0
N14—C10—C11	100.73 (9)	C20—C21—H21	120.0
N14—C10—C9	110.50 (9)	C17'—C16'—C21'	117.0 (18)
C11—C10—C9	112.80 (9)	C17'—C16'—C15	120.0 (18)
N14—C10—H10	110.8	C21'—C16'—C15	123.0 (16)
C11—C10—H10	110.8	C16'—C17'—C18'	122.8 (14)
C9—C10—H10	110.8	C16'—C17'—H17'	118.6
O11—C11—N12	126.63 (11)	C18'—C17'—H17'	118.6
O11—C11—C10	123.45 (11)	C19'—C18'—C17'	117.6 (12)
N12—C11—C10	109.88 (10)	C19'—C18'—H18'	121.2
C13—N12—C11	105.83 (10)	C17'—C18'—H18'	121.2
C13—N13—H13A	120.0	C20'—C19'—C18'	120.5 (16)
C13—N13—H13B	120.0	C20'—C19'—H19'	119.8
H13A—N13—H13B	120.0	C18'—C19'—H19'	119.8
N13—C13—N14	122.37 (11)	C19'—C20'—C21'	119.9 (19)
N13—C13—N12	122.79 (11)	C19'—C20'—H20'	120.0
N14—C13—N12	114.84 (10)	C21'—C20'—H20'	120.0
C13—N14—C10	108.04 (9)	C16'—C21'—C20'	122.2 (19)
C13—N14—C14	125.31 (10)	C16'—C21'—H21'	118.9
C10—N14—C14	126.52 (10)	C20'—C21'—H21'	118.9
N14—C14—H14A	109.5

O1—C1—N2—C3	−176.47 (11)	O11—C11—N12—C13	−179.47 (11)
C9—C1—N2—C3	3.04 (13)	C10—C11—N12—C13	−1.45 (12)
O1—C1—N2—C15	5.67 (19)	C11—N12—C13—N13	175.47 (11)
C9—C1—N2—C15	−174.83 (10)	C11—N12—C13—N14	−4.15 (13)
C1—N2—C3—C4	−179.33 (13)	N13—C13—N14—C10	−171.44 (10)
C15—N2—C3—C4	−1.5 (2)	N12—C13—N14—C10	8.18 (13)
C1—N2—C3—C8	1.47 (14)	N13—C13—N14—C14	12.39 (18)
C15—N2—C3—C8	179.33 (11)	N12—C13—N14—C14	−167.99 (10)
C8—C3—C4—C5	1.9 (2)	C11—C10—N14—C13	−7.92 (11)
N2—C3—C4—C5	−177.19 (13)	C9—C10—N14—C13	111.54 (10)
C3—C4—C5—C6	0.3 (2)	C11—C10—N14—C14	168.19 (10)
C4—C5—C6—C7	−1.5 (2)	C9—C10—N14—C14	−72.35 (14)
C5—C6—C7—C8	0.5 (2)	C1—N2—C15—C16'	−101.9 (9)
C6—C7—C8—C3	1.71 (19)	C3—N2—C15—C16'	80.6 (9)
C6—C7—C8—C9	−176.14 (13)	C1—N2—C15—C16	−109.52 (19)
C4—C3—C8—C7	−3.0 (2)	C3—N2—C15—C16	72.9 (2)
N2—C3—C8—C7	176.26 (11)	C16'—C15—C16—C21	−62 (8)
C4—C3—C8—C9	175.30 (12)	N2—C15—C16—C21	50.4 (3)
N2—C3—C8—C9	−5.45 (14)	C16'—C15—C16—C17	113 (8)
C7—C8—C9—O9	−55.07 (17)	N2—C15—C16—C17	−134.8 (2)
C3—C8—C9—O9	126.90 (11)	C21—C16—C17—C18	0.11 (19)
C7—C8—C9—C1	−175.25 (13)	C15—C16—C17—C18	−174.8 (2)
C3—C8—C9—C1	6.72 (12)	C16—C17—C18—C19	−0.1 (2)
C7—C8—C9—C10	68.94 (17)	C17—C18—C19—C20	0.0 (4)
C3—C8—C9—C10	−109.09 (11)	C18—C19—C20—C21	0.1 (4)
O1—C1—C9—O9	53.15 (15)	C17—C16—C21—C20	0.0 (3)
N2—C1—C9—O9	−126.36 (11)	C15—C16—C21—C20	174.8 (2)
O1—C1—C9—C8	173.61 (11)	C19—C20—C21—C16	−0.1 (4)
N2—C1—C9—C8	−5.89 (12)	N2—C15—C16'—C17'	−161.4 (9)
O1—C1—C9—C10	−69.22 (15)	C16—C15—C16'—C17'	−91 (8)
N2—C1—C9—C10	111.28 (11)	N2—C15—C16'—C21'	22.3 (12)
O9—C9—C10—N14	67.00 (12)	C16—C15—C16'—C21'	93 (8)
C8—C9—C10—N14	−58.33 (12)	C21'—C16'—C17'—C18'	−0.1 (3)
C1—C9—C10—N14	−169.48 (10)	C15—C16'—C17'—C18'	−176.5 (14)
O9—C9—C10—C11	178.88 (9)	C16'—C17'—C18'—C19'	−0.1 (3)
C8—C9—C10—C11	53.55 (13)	C17'—C18'—C19'—C20'	0.2 (7)
C1—C9—C10—C11	−57.60 (12)	C18'—C19'—C20'—C21'	−0.2 (9)
N14—C10—C11—O11	−176.13 (11)	C17'—C16'—C21'—C20'	0.1 (7)
C9—C10—C11—O11	66.08 (14)	C15—C16'—C21'—C20'	176.5 (14)
N14—C10—C11—N12	5.78 (12)	C19'—C20'—C21'—C16'	0.0 (10)
C9—C10—C11—N12	−112.01 (11)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O9—H9···N12ⁱ	0.84	1.97	2.8065 (13)	175
N13—H13A···O11ⁱⁱ	0.88	2.24	2.9321 (13)	135
N13—H13B···O1ⁱⁱⁱ	0.88	1.97	2.8410 (14)	173

Symmetry codes: (i) −x+1, y−1/2, −z+3/2; (ii) x+1/2, y, −z+3/2; (iii) −x+1, y+1/2, −z+3/2.

Experimental details

Crystal data
Chemical formula	C₁₉H₁₈N₄O₃
M_r	350.37
Crystal system, space group	Orthorhombic, Pbca
Temperature (K)	90
a, b, c (Å)	13.4466 (2), 10.6921 (2), 27.2057 (5)
V (Å³)	3911.43 (12)
Z	8
Radiation type	Cu Kα
µ (mm⁻¹)	0.68
Crystal size (mm)	0.12 × 0.10 × 0.04

Data collection
Diffractometer	Bruker X8 Proteum CCD diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2006)
T_min, T_max	0.911, 0.973
No. of measured, independent and observed [I > 2σ(I)] reflections	55165, 3602, 3344
R_int	0.043
(sin θ/λ)_max (Å⁻¹)	0.604

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.038, 0.104, 1.04
No. of reflections	3602
No. of parameters	287
No. of restraints	222
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.28, −0.30

Computer programs: APEX2 (Bruker, 2006), SAINT (Bruker, 2006), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), XP (Sheldrick, 2008), SHELX97 (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O9—H9···N12ⁱ	0.84	1.97	2.8065 (13)	175
N13—H13A···O11ⁱⁱ	0.88	2.24	2.9321 (13)	135
N13—H13B···O1ⁱⁱⁱ	0.88	1.97	2.8410 (14)	173

Symmetry codes: (i) −x+1, y−1/2, −z+3/2; (ii) x+1/2, y, −z+3/2; (iii) −x+1, y+1/2, −z+3/2.

Acknowledgements

This investigation was supported by NIH/National Cancer Institute grant RO1 CA140409.

References

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