rac-5-Bromo-N-benzyl­isatincreatinine ethanol monosolvate

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

doi:10.1107/S160053681300038X

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 69| Part 2| February 2013| Pages o288-o289

doi:10.1107/S160053681300038X

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rac-5-Bromo-N-benzylisatincreatinine ethanol monosolvate

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)

In the title compound [systematic name: rac-1-benzyl-5-bromo-3-hydroxy-3-(2-imino-3-methyl-5-oxoimidazolidin-4-yl)-2,3-dihydro-1H-indol-2-one ethanol monosolvate], C₁₉H₁₇BrN₄O₃·C₂H₅OH, which crystallized as a racemate (RR and SS), the isatin ring is almost planar, with an r.m.s. deviations from the mean plane of 0.0276 (14) Å. The phenyl ring of the benzyl group makes a dihedral angle with the mean plane of the isatin ring of 87.40 (5)° and the dihedral angle between the imidazole and isatin rings is 58.56 (7)°. In the crystal, molecules are linked into two-dimensional pleated-sheet networks in the ac plane formed by O—H⋯O, N—H⋯O and O—H⋯N hydrogen bonds; within these sheets there are R₄⁴(10) rings that involve three molecules of the title compound and a single ethanol solvent molecule. In addition, there are π–π interactions between inversion-related benzyl groups, with an interplanar spacing of 3.444 (3) Å.

Related literature

Background information on the biological importance of isatins has been given by Pandeya et al. (2005 ), and by Vine et al. (2007 ). For similar structures, see: Tang et al. (2009 ); Penthala et al. (2009a ,b ).

Experimental

Crystal data

C₁₉H₁₇BrN₄O₃·C₂H₆O
M_r = 475.34
Monoclinic, P 2₁ /n
a = 7.8384 (16) Å
b = 24.553 (5) Å
c = 10.936 (2) Å
β = 99.54 (3)°
V = 2075.6 (7) Å³
Z = 4
Mo Kα radiation
μ = 2.02 mm⁻¹
T = 90 K
0.20 × 0.15 × 0.10 mm

Data collection

Nonius KappaCCD diffractometer
Absorption correction: multi-scan [SCALEPACK (Otwinowski & Minor, 1997 ) and XABS2 (Parkin et al., 1995 )] T_min = 0.689, T_max = 0.824
41507 measured reflections
4752 independent reflections
4147 reflections with I > 2σ(I)
R_int = 0.038

Refinement

R[F² > 2σ(F²)] = 0.029
wR(F²) = 0.074
S = 1.05
4752 reflections
282 parameters
3 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 1.19 e Å⁻³
Δρ_min = −0.45 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O9—H9⋯O1Sⁱ	0.84	1.87	2.694 (2)	169
N13—H13A⋯O11ⁱⁱ	0.81 (2)	2.00 (2)	2.811 (2)	171 (2)
N13—H13B⋯O9ⁱⁱⁱ	0.82 (2)	2.36 (2)	2.933 (2)	128 (2)
N13—H13B⋯O1ⁱⁱⁱ	0.82 (2)	2.46 (2)	3.158 (2)	144 (2)
O1S—H1S⋯N12	0.84	1.91	2.745 (2)	174
Symmetry codes: (i) x+1, y, z; (ii) $[x+{\script{1\over 2}}, -y+{\script{1\over 2}}, z+{\script{1\over 2}}]$ ; (iii) $[x-{\script{1\over 2}}, -y+{\script{1\over 2}}, z+{\script{1\over 2}}]$ .

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/S160053681300038X/hg5279sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S160053681300038X/hg5279Isup2.hkl

Supporting information file. DOI: 10.1107/S160053681300038X/hg5279Isup3.cml

checkCIF report

Comment top

In view of the biological importance of isatins (Pandeya et al., 2005; Vine et al., 2007) we have synthesized a series of novel compounds containing isatin and creatinine moieties to screen for their anticancer activity. The title compound was prepared by the aldol condensation of 5-bromo-N-benzylindol-2,3-dione (5-bromo-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 substitituents (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. The compound crystallized as a racemate (RR and SS). The molecular structure of title compound is shown in Fig. 1. The isatin ring is almost planar with r.m.s deviation from the mean plane of 0.0276 (14) Å, 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 87.40 (5)°. In the title compound the molecules are linked into 2-D pleated-sheet networks in the ac plane by O—H···O, N—H···O and O—H···N hydrogen bonds. Within these sheets there are R⁴₄(10) rings that involve three molecules of the title compound and a single ethanol solvent molecule.

Related literature top

Background information on the biological importance of isatins has been given by Pandeya et al. (2005), and by Vine et al. (2007). 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 a pale-yellow crystalline product that was suitable for X-ray analysis. Spectroscopic data for rac-5-bromo-N-benzylisatin creatinine: ¹H NMR(DMSO-d₆): δ 3.2 0 (s, 3H, CH₃), 4.22 (s, 1H, CH), 4.74–4.92 (ABq, 2H, CH₂), 6.62–6.64 (d, J=8.1 Hz, 1H, C₇H), 6.74 (s, 1H, OH), 7.19–7.20 (d, J=1.5 Hz, 1H,-C₄H), 7.25–7.46 (m, 6H, C₅H, C₆H, Ar—H), 7.82 (bs, 2H, NH₂); ¹³C NMR (DMSO-d₆): δ 32.71, 42.76, 69.61, 75.87, 110.43, 123.55, 125.67, 126.89, 127.05 (2 C), 128.21 (2 C), 129.01, 129.17, 135.39, 141.91, 172.10 (C=N), 173.98 (isatin C=O), 181.93 (creatinine C=O).

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 displacement ellipsoids drawn at the 50% probability level.
	Fig. 2. Hydrogen bonding in the crystal structure of the title compound. Dashed lines represent hydrogen bonds, while the open bonds indicate continuation of the structure, approximately in the (0 1 - 1) direction.

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

Crystal data top

C₁₉H₁₇BrN₄O₃·C₂H₆O	F(000) = 976
M_r = 475.34	D_x = 1.521 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 51652 reflections
a = 7.8384 (16) Å	θ = 1.0–27.5°
b = 24.553 (5) Å	µ = 2.02 mm⁻¹
c = 10.936 (2) Å	T = 90 K
β = 99.54 (3)°	Block, colourless
V = 2075.6 (7) Å³	0.20 × 0.15 × 0.10 mm
Z = 4

Data collection top

Nonius KappaCCD diffractometer	4752 independent reflections
Radiation source: fine-focus sealed tube	4147 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.038
Detector resolution: 9.1 pixels mm^-1	θ_max = 27.5°, θ_min = 1.7°
ω scans at fixed χ = 55°	h = −10→10
Absorption correction: multi-scan [SCALEPACK (Otwinowski & Minor, 1997) and XABS2 (Parkin et al., 1995)]	k = −31→31
T_min = 0.689, T_max = 0.824	l = −14→14
41507 measured reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.029	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.074	H atoms treated by a mixture of independent and constrained refinement
S = 1.05	w = 1/[σ²(F_o²) + (0.0318P)² + 2.2794P] where P = (F_o² + 2F_c²)/3
4752 reflections	(Δ/σ)_max = 0.002
282 parameters	Δρ_max = 1.19 e Å⁻³
3 restraints	Δρ_min = −0.45 e Å⁻³

Crystal data top

C₁₉H₁₇BrN₄O₃·C₂H₆O	V = 2075.6 (7) Å³
M_r = 475.34	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 7.8384 (16) Å	µ = 2.02 mm⁻¹
b = 24.553 (5) Å	T = 90 K
c = 10.936 (2) Å	0.20 × 0.15 × 0.10 mm
β = 99.54 (3)°

Data collection top

Nonius KappaCCD diffractometer	4752 independent reflections
Absorption correction: multi-scan [SCALEPACK (Otwinowski & Minor, 1997) and XABS2 (Parkin et al., 1995)]	4147 reflections with I > 2σ(I)
T_min = 0.689, T_max = 0.824	R_int = 0.038
41507 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.029	3 restraints
wR(F²) = 0.074	H atoms treated by a mixture of independent and constrained refinement
S = 1.05	Δρ_max = 1.19 e Å⁻³
4752 reflections	Δρ_min = −0.45 e Å⁻³
282 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-value wR and goodness of fit S are based on F². Conventional R-values 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-values based on F² are statistically about twice as large as those based on F, and R-values 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
Br1	0.49690 (3)	0.374439 (8)	0.816959 (17)	0.02004 (7)
O1	0.41024 (17)	0.35297 (6)	0.10785 (12)	0.0171 (3)
C1	0.4044 (2)	0.36264 (7)	0.21623 (17)	0.0130 (3)
N2	0.35261 (19)	0.41049 (6)	0.26345 (14)	0.0131 (3)
C3	0.3743 (2)	0.40838 (7)	0.39354 (17)	0.0127 (3)
C4	0.3378 (2)	0.44865 (8)	0.47375 (18)	0.0152 (4)
H4	0.2896	0.4825	0.4435	0.018*
C5	0.3745 (2)	0.43786 (8)	0.60104 (17)	0.0160 (4)
H5	0.3503	0.4646	0.6587	0.019*
C6	0.4460 (2)	0.38823 (8)	0.64338 (16)	0.0140 (4)
C7	0.4822 (2)	0.34757 (7)	0.56274 (16)	0.0129 (3)
H7	0.5311	0.3138	0.5931	0.015*
C8	0.4445 (2)	0.35808 (7)	0.43654 (17)	0.0121 (3)
O9	0.64140 (16)	0.31074 (6)	0.31688 (12)	0.0163 (3)
H9	0.7024	0.3118	0.3877	0.024*
C9	0.4680 (2)	0.32370 (7)	0.32616 (16)	0.0124 (3)
C10	0.3592 (2)	0.27084 (7)	0.31485 (16)	0.0123 (3)
H10	0.3696	0.2511	0.2364	0.015*
O11	0.07782 (17)	0.31156 (5)	0.24552 (12)	0.0169 (3)
C11	0.1692 (2)	0.28271 (7)	0.32180 (16)	0.0127 (3)
N12	0.12428 (19)	0.25919 (6)	0.42372 (14)	0.0137 (3)
N13	0.2659 (2)	0.20205 (7)	0.57992 (15)	0.0166 (3)
H13A	0.356 (3)	0.1946 (9)	0.625 (2)	0.020*
H13B	0.175 (3)	0.2005 (10)	0.608 (2)	0.020*
C13	0.2659 (2)	0.23119 (7)	0.47904 (16)	0.0128 (3)
N14	0.40463 (19)	0.23525 (6)	0.42122 (14)	0.0121 (3)
C14	0.5592 (2)	0.20123 (8)	0.44579 (18)	0.0177 (4)
H14A	0.6453	0.2187	0.5088	0.026*
H14B	0.6073	0.1967	0.3692	0.026*
H14C	0.5288	0.1655	0.4758	0.026*
C15	0.3028 (2)	0.45903 (8)	0.18962 (17)	0.0156 (4)
H15A	0.3328	0.4536	0.1060	0.019*
H15B	0.3718	0.4902	0.2282	0.019*
C16	0.1127 (2)	0.47366 (8)	0.17564 (16)	0.0146 (4)
C17	−0.0132 (3)	0.43353 (8)	0.17080 (19)	0.0197 (4)
H17	0.0203	0.3965	0.1834	0.024*
C18	−0.1880 (3)	0.44717 (8)	0.14763 (19)	0.0204 (4)
H18	−0.2733	0.4195	0.1438	0.024*
C19	−0.2373 (3)	0.50119 (8)	0.13010 (18)	0.0187 (4)
H19	−0.3564	0.5106	0.1133	0.022*
C20	−0.1119 (3)	0.54152 (8)	0.13722 (19)	0.0198 (4)
H20	−0.1454	0.5786	0.1266	0.024*
C21	0.0624 (3)	0.52780 (8)	0.15986 (18)	0.0181 (4)
H21	0.1476	0.5556	0.1646	0.022*
O1S	−0.13483 (17)	0.30418 (6)	0.53172 (13)	0.0191 (3)
H1S	−0.0600	0.2885	0.4975	0.029*
C1S	−0.0616 (3)	0.35257 (9)	0.5930 (2)	0.0249 (4)
H1S1	0.0641	0.3470	0.6199	0.030*
H1S2	−0.1143	0.3588	0.6680	0.030*
C2S	−0.0892 (3)	0.40229 (9)	0.5114 (2)	0.0300 (5)
H2S1	−0.0366	0.3965	0.4372	0.045*
H2S2	−0.0355	0.4339	0.5570	0.045*
H2S3	−0.2135	0.4088	0.4869	0.045*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Br1	0.02698 (11)	0.02127 (11)	0.01143 (10)	0.00486 (8)	0.00183 (7)	−0.00050 (7)
O1	0.0183 (7)	0.0219 (7)	0.0113 (6)	−0.0017 (6)	0.0030 (5)	0.0000 (5)
C1	0.0084 (8)	0.0169 (9)	0.0139 (9)	−0.0023 (6)	0.0026 (6)	0.0011 (7)
N2	0.0139 (7)	0.0146 (7)	0.0108 (7)	−0.0001 (6)	0.0016 (6)	0.0019 (6)
C3	0.0094 (8)	0.0160 (9)	0.0125 (8)	−0.0025 (7)	0.0010 (6)	0.0011 (7)
C4	0.0140 (8)	0.0131 (8)	0.0180 (9)	0.0005 (7)	0.0014 (7)	0.0005 (7)
C5	0.0157 (9)	0.0167 (9)	0.0157 (9)	−0.0001 (7)	0.0029 (7)	−0.0033 (7)
C6	0.0130 (8)	0.0191 (9)	0.0094 (8)	−0.0015 (7)	0.0005 (7)	−0.0006 (7)
C7	0.0105 (8)	0.0151 (9)	0.0129 (8)	0.0000 (7)	0.0016 (7)	0.0012 (7)
C8	0.0081 (8)	0.0144 (8)	0.0140 (9)	−0.0019 (6)	0.0028 (6)	−0.0006 (7)
O9	0.0104 (6)	0.0260 (7)	0.0129 (6)	0.0032 (5)	0.0033 (5)	−0.0005 (5)
C9	0.0103 (8)	0.0157 (9)	0.0113 (8)	0.0014 (7)	0.0019 (6)	0.0010 (7)
C10	0.0129 (8)	0.0137 (8)	0.0102 (8)	0.0018 (7)	0.0016 (6)	0.0004 (7)
O11	0.0148 (6)	0.0168 (7)	0.0174 (7)	−0.0004 (5)	−0.0025 (5)	0.0033 (5)
C11	0.0111 (8)	0.0121 (8)	0.0138 (9)	−0.0012 (6)	−0.0006 (7)	−0.0023 (7)
N12	0.0112 (7)	0.0151 (7)	0.0144 (7)	0.0011 (6)	0.0013 (6)	0.0023 (6)
N13	0.0123 (8)	0.0232 (9)	0.0146 (8)	0.0022 (7)	0.0033 (6)	0.0049 (6)
C13	0.0123 (8)	0.0130 (8)	0.0128 (8)	−0.0010 (7)	0.0014 (7)	−0.0015 (7)
N14	0.0117 (7)	0.0134 (7)	0.0116 (7)	0.0031 (6)	0.0031 (6)	0.0025 (6)
C14	0.0159 (9)	0.0185 (9)	0.0197 (10)	0.0076 (7)	0.0063 (7)	0.0034 (7)
C15	0.0160 (9)	0.0150 (9)	0.0155 (9)	−0.0009 (7)	0.0019 (7)	0.0044 (7)
C16	0.0168 (9)	0.0173 (9)	0.0095 (8)	0.0000 (7)	0.0017 (7)	0.0019 (7)
C17	0.0192 (10)	0.0152 (9)	0.0243 (10)	0.0004 (7)	0.0026 (8)	0.0040 (8)
C18	0.0175 (9)	0.0189 (10)	0.0254 (10)	−0.0036 (8)	0.0051 (8)	0.0021 (8)
C19	0.0179 (9)	0.0234 (10)	0.0152 (9)	0.0041 (8)	0.0044 (7)	0.0023 (8)
C20	0.0232 (10)	0.0153 (9)	0.0214 (10)	0.0034 (8)	0.0055 (8)	0.0009 (7)
C21	0.0201 (9)	0.0164 (9)	0.0182 (9)	−0.0028 (8)	0.0044 (7)	−0.0006 (7)
O1S	0.0127 (6)	0.0229 (7)	0.0217 (7)	0.0024 (5)	0.0033 (5)	−0.0021 (6)
C1S	0.0218 (10)	0.0275 (11)	0.0240 (11)	0.0005 (9)	−0.0002 (8)	−0.0052 (9)
C2S	0.0239 (11)	0.0286 (12)	0.0376 (13)	−0.0076 (9)	0.0049 (10)	0.0006 (10)

Geometric parameters (Å, º) top

Br1—C6	1.9042 (18)	C13—N14	1.349 (2)
O1—C1	1.217 (2)	N14—C14	1.460 (2)
C1—N2	1.372 (2)	C14—H14A	0.9800
C1—C9	1.552 (2)	C14—H14B	0.9800
N2—C3	1.406 (2)	C14—H14C	0.9800
N2—C15	1.456 (2)	C15—C16	1.516 (3)
C3—C4	1.383 (3)	C15—H15A	0.9900
C3—C8	1.401 (3)	C15—H15B	0.9900
C4—C5	1.399 (3)	C16—C17	1.389 (3)
C4—H4	0.9500	C16—C21	1.389 (3)
C5—C6	1.388 (3)	C17—C18	1.392 (3)
C5—H5	0.9500	C17—H17	0.9500
C6—C7	1.392 (3)	C18—C19	1.386 (3)
C7—C8	1.387 (3)	C18—H18	0.9500
C7—H7	0.9500	C19—C20	1.388 (3)
C8—C9	1.509 (2)	C19—H19	0.9500
O9—C9	1.416 (2)	C20—C21	1.389 (3)
O9—H9	0.8400	C20—H20	0.9500
C9—C10	1.546 (2)	C21—H21	0.9500
C10—N14	1.451 (2)	O1S—C1S	1.436 (3)
C10—C11	1.532 (2)	O1S—H1S	0.8400
C10—H10	1.0000	C1S—C2S	1.506 (3)
O11—C11	1.230 (2)	C1S—H1S1	0.9900
C11—N12	1.353 (2)	C1S—H1S2	0.9900
N12—C13	1.359 (2)	C2S—H2S1	0.9800
N13—C13	1.315 (2)	C2S—H2S2	0.9800
N13—H13A	0.81 (2)	C2S—H2S3	0.9800
N13—H13B	0.82 (2)

O1—C1—N2	126.51 (17)	C13—N14—C10	108.09 (14)
O1—C1—C9	125.11 (17)	C13—N14—C14	125.49 (15)
N2—C1—C9	108.24 (15)	C10—N14—C14	125.31 (15)
C1—N2—C3	110.84 (15)	N14—C14—H14A	109.5
C1—N2—C15	124.14 (16)	N14—C14—H14B	109.5
C3—N2—C15	124.60 (15)	H14A—C14—H14B	109.5
C4—C3—C8	121.89 (17)	N14—C14—H14C	109.5
C4—C3—N2	127.78 (17)	H14A—C14—H14C	109.5
C8—C3—N2	110.31 (16)	H14B—C14—H14C	109.5
C3—C4—C5	117.77 (17)	N2—C15—C16	114.75 (15)
C3—C4—H4	121.1	N2—C15—H15A	108.6
C5—C4—H4	121.1	C16—C15—H15A	108.6
C6—C5—C4	120.19 (17)	N2—C15—H15B	108.6
C6—C5—H5	119.9	C16—C15—H15B	108.6
C4—C5—H5	119.9	H15A—C15—H15B	107.6
C5—C6—C7	122.12 (17)	C17—C16—C21	119.26 (18)
C5—C6—Br1	119.66 (14)	C17—C16—C15	121.06 (17)
C7—C6—Br1	118.22 (14)	C21—C16—C15	119.56 (17)
C8—C7—C6	117.69 (17)	C16—C17—C18	120.50 (18)
C8—C7—H7	121.2	C16—C17—H17	119.7
C6—C7—H7	121.2	C18—C17—H17	119.7
C7—C8—C3	120.34 (17)	C19—C18—C17	119.93 (18)
C7—C8—C9	131.13 (17)	C19—C18—H18	120.0
C3—C8—C9	108.53 (15)	C17—C18—H18	120.0
C9—O9—H9	109.5	C18—C19—C20	119.74 (18)
O9—C9—C8	115.38 (15)	C18—C19—H19	120.1
O9—C9—C10	109.18 (14)	C20—C19—H19	120.1
C8—C9—C10	113.26 (14)	C19—C20—C21	120.23 (18)
O9—C9—C1	105.76 (14)	C19—C20—H20	119.9
C8—C9—C1	102.06 (14)	C21—C20—H20	119.9
C10—C9—C1	110.69 (14)	C20—C21—C16	120.32 (18)
N14—C10—C11	100.72 (14)	C20—C21—H21	119.8
N14—C10—C9	112.50 (14)	C16—C21—H21	119.8
C11—C10—C9	111.34 (14)	C1S—O1S—H1S	109.5
N14—C10—H10	110.6	O1S—C1S—C2S	112.79 (18)
C11—C10—H10	110.6	O1S—C1S—H1S1	109.0
C9—C10—H10	110.6	C2S—C1S—H1S1	109.0
O11—C11—N12	127.07 (17)	O1S—C1S—H1S2	109.0
O11—C11—C10	122.53 (16)	C2S—C1S—H1S2	109.0
N12—C11—C10	110.35 (15)	H1S1—C1S—H1S2	107.8
C11—N12—C13	106.12 (15)	C1S—C2S—H2S1	109.5
C13—N13—H13A	121.0 (16)	C1S—C2S—H2S2	109.5
C13—N13—H13B	117.3 (16)	H2S1—C2S—H2S2	109.5
H13A—N13—H13B	118 (2)	C1S—C2S—H2S3	109.5
N13—C13—N14	123.05 (17)	H2S1—C2S—H2S3	109.5
N13—C13—N12	122.36 (16)	H2S2—C2S—H2S3	109.5
N14—C13—N12	114.59 (16)

O1—C1—N2—C3	−175.80 (17)	C8—C9—C10—N14	−61.17 (19)
C9—C1—N2—C3	0.11 (19)	C1—C9—C10—N14	−175.10 (14)
O1—C1—N2—C15	−2.9 (3)	O9—C9—C10—C11	−178.91 (14)
C9—C1—N2—C15	172.95 (15)	C8—C9—C10—C11	51.04 (19)
C1—N2—C3—C4	179.53 (18)	C1—C9—C10—C11	−62.89 (18)
C15—N2—C3—C4	6.7 (3)	N14—C10—C11—O11	−178.92 (16)
C1—N2—C3—C8	0.7 (2)	C9—C10—C11—O11	61.6 (2)
C15—N2—C3—C8	−172.11 (16)	N14—C10—C11—N12	3.60 (19)
C8—C3—C4—C5	0.4 (3)	C9—C10—C11—N12	−115.88 (16)
N2—C3—C4—C5	−178.32 (17)	O11—C11—N12—C13	179.74 (18)
C3—C4—C5—C6	0.4 (3)	C10—C11—N12—C13	−2.93 (19)
C4—C5—C6—C7	−0.6 (3)	C11—N12—C13—N13	−178.18 (17)
C4—C5—C6—Br1	179.46 (14)	C11—N12—C13—N14	1.0 (2)
C5—C6—C7—C8	0.0 (3)	N13—C13—N14—C10	−179.41 (17)
Br1—C6—C7—C8	179.97 (13)	N12—C13—N14—C10	1.4 (2)
C6—C7—C8—C3	0.7 (3)	N13—C13—N14—C14	12.2 (3)
C6—C7—C8—C9	179.66 (17)	N12—C13—N14—C14	−167.02 (17)
C4—C3—C8—C7	−1.0 (3)	C11—C10—N14—C13	−2.85 (18)
N2—C3—C8—C7	177.94 (15)	C9—C10—N14—C13	115.79 (16)
C4—C3—C8—C9	179.88 (16)	C11—C10—N14—C14	165.59 (16)
N2—C3—C8—C9	−1.21 (19)	C9—C10—N14—C14	−75.8 (2)
C7—C8—C9—O9	−63.7 (3)	C1—N2—C15—C16	111.7 (2)
C3—C8—C9—O9	115.31 (17)	C3—N2—C15—C16	−76.5 (2)
C7—C8—C9—C10	63.1 (2)	N2—C15—C16—C17	−33.1 (3)
C3—C8—C9—C10	−117.84 (16)	N2—C15—C16—C21	150.87 (17)
C7—C8—C9—C1	−177.84 (18)	C21—C16—C17—C18	1.4 (3)
C3—C8—C9—C1	1.18 (18)	C15—C16—C17—C18	−174.63 (18)
O1—C1—C9—O9	54.1 (2)	C16—C17—C18—C19	−0.5 (3)
N2—C1—C9—O9	−121.83 (15)	C17—C18—C19—C20	−0.8 (3)
O1—C1—C9—C8	175.19 (17)	C18—C19—C20—C21	1.0 (3)
N2—C1—C9—C8	−0.78 (18)	C19—C20—C21—C16	0.0 (3)
O1—C1—C9—C10	−64.0 (2)	C17—C16—C21—C20	−1.2 (3)
N2—C1—C9—C10	120.05 (16)	C15—C16—C21—C20	174.94 (17)
O9—C9—C10—N14	68.89 (18)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O9—H9···O1Sⁱ	0.84	1.87	2.694 (2)	169
N13—H13A···O11ⁱⁱ	0.81 (2)	2.00 (2)	2.811 (2)	171 (2)
N13—H13B···O9ⁱⁱⁱ	0.82 (2)	2.36 (2)	2.933 (2)	128 (2)
N13—H13B···O1ⁱⁱⁱ	0.82 (2)	2.46 (2)	3.158 (2)	144 (2)
O1S—H1S···N12	0.84	1.91	2.745 (2)	174

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

Experimental details

Crystal data
Chemical formula	C₁₉H₁₇BrN₄O₃·C₂H₆O
M_r	475.34
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	90
a, b, c (Å)	7.8384 (16), 24.553 (5), 10.936 (2)
β (°)	99.54 (3)
V (Å³)	2075.6 (7)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	2.02
Crystal size (mm)	0.20 × 0.15 × 0.10

Data collection
Diffractometer	Nonius KappaCCD diffractometer
Absorption correction	Multi-scan [SCALEPACK (Otwinowski & Minor, 1997) and XABS2 (Parkin et al., 1995)]
T_min, T_max	0.689, 0.824
No. of measured, independent and observed [I > 2σ(I)] reflections	41507, 4752, 4147
R_int	0.038
(sin θ/λ)_max (Å⁻¹)	0.649

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.029, 0.074, 1.05
No. of reflections	4752
No. of parameters	282
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)	1.19, −0.45

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.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O9—H9···O1Sⁱ	0.84	1.87	2.694 (2)	168.6
N13—H13A···O11ⁱⁱ	0.81 (2)	2.00 (2)	2.811 (2)	171 (2)
N13—H13B···O9ⁱⁱⁱ	0.82 (2)	2.36 (2)	2.933 (2)	128 (2)
N13—H13B···O1ⁱⁱⁱ	0.82 (2)	2.46 (2)	3.158 (2)	144 (2)
O1S—H1S···N12	0.84	1.91	2.745 (2)	174.2

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

Acknowledgements

This investigation was supported by NIH/National Cancer Institute grant PO1 CA140409. We thank Dr S. Parkin, University of Kentucky, for X-ray crystallographic services.

References

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