3-(2-Amino-1-methyl-4-oxo-4,5-dihydro-1H-imidazol-5-yl)-3-hydr­oxy-1-phenyl­indolin-2-one ethanol solvate

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

doi:10.1107/S1600536809033881

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 65| Part 10| October 2009| Pages o2439-o2440

doi:10.1107/S1600536809033881

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3-(2-Amino-1-methyl-4-oxo-4,5-dihydro-1H-imidazol-5-yl)-3-hydroxy-1-phenylindolin-2-one ethanol solvate

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@email.uky.edu

(Received 18 August 2009; accepted 24 August 2009; online 12 September 2009)

In the title compound, C₁₈H₁₆N₄O₃·C₂H₅OH, molecules are linked into chains by a series of intermolecular N—H⋯O, N—H⋯N and O—H⋯O hydrogen bonds which stabilize the crystal structure. The indole and creatinine units make a dihedral angle of 56.45 (4)°. The title compound has two chiral centres. The crystal structure indicates the compound is racemic (RR and SS).

Related literature

For the biological activity of isatin and its derivatives, see: Pandeya et al. (2005 ). The endogenous oxindoles 5-hydroxyoxindole and isatin are antiproliferative and proapoptotic, see: Cane et al. (2000 ). For in vitro cytotoxicity evaluation of some substituted isatin derivatives, see: Vine et al. (2007 ). 2-Indol-3-yl-methylenequinuclidin-3-ols and NADPH oxidase activity has been reported by Sekhar et al. (2003 ), and novel substituted (Z)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-one and (Z)-(±)-2-(N-benzylindol-3-yl methylene)quinuclidin-3-ol derivatives as potent thermal sensitizing agents by Sonar et al. (2007 ). For the crystal and molecular structure of isatin, see: Frolova et al. (1988 ). For the structure of 3-(2-amino-1-methyl-4-oxo-4,5-dihydro-1H-imidazol-5-yl)-3-hydroxyindolin-2-one monohydrate, see: Penthala et al. (2009 ) and of 1,1′-diacetyl-3-hydroxy-2,2′,3,3′-tetrahydro-3,3′-bi(1H-indole)-2,2′-dione, see: Usman et al. (2002 ). The aldol condensation enolate mechanism via a six-membered transition state has been described by Zimmerman & Traxler (1957 ).

Experimental

Crystal data

C₁₈H₁₆N₄O₃·C₂H₆O
M_r = 382.42
Triclinic, $[P \overline 1]$
a = 7.4912 (1) Å
b = 11.0018 (2) Å
c = 12.0835 (2) Å
α = 78.152 (1)°
β = 74.413 (1)°
γ = 74.090 (1)°
V = 913.15 (3) Å³
Z = 2
Cu Kα radiation
μ = 0.82 mm⁻¹
T = 90 K
0.11 × 0.11 × 0.08 mm

Data collection

Bruker X8 Proteum diffractometer
Absorption correction: multi-scan (SADABS in APEX2; Bruker, 2006 ) T_min = 0.828, T_max = 0.938
13576 measured reflections
3294 independent reflections
3126 reflections with I > 2σ(I)
R_int = 0.035

Refinement

R[F² > 2σ(F²)] = 0.037
wR(F²) = 0.098
S = 1.07
3294 reflections
258 parameters
H-atom parameters constrained
Δρ_max = 0.37 e Å⁻³
Δρ_min = −0.41 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯O1S	0.84	2.19	2.9579 (14)	152
O2—H2⋯O3ⁱ	0.84	2.58	3.2440 (12)	137
N3—H3A⋯O1ⁱⁱ	0.88	2.02	2.8898 (13)	169
N3—H3B⋯N2ⁱⁱⁱ	0.88	2.06	2.9391 (15)	174
O1S—H1S⋯O3ⁱ	0.84	1.89	2.7048 (13)	162
Symmetry codes: (i) x+1, y, z; (ii) -x+1, -y, -z; (iii) -x, -y, -z.

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: SHELXL97 and local procedures.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809033881/hg2557sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809033881/hg2557Isup2.hkl

checkCIF report

Comment top

1H-Indole-2,3-diones (isatins) are versatile molecules that display diverse biological activities, (Pandeya et al., 2005), including anticancer activity. (Cane et al., 2000 and Vine et al., 2007). Based on the results of earlier work on radiosensitizers such as (Z)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-one and (Z)-(±)-2-(N-benzylindol-3-ylmethylene) quinuclidin-3-ol derivatives (Sekhar et al., 2003; Sonar et al., 2007), we have carried out the design, synthesis and structural analysis of a series of 3-(2-amino-1-methyl-4-oxo-4,5-dihydro-1H-imidazol-5-yl)-3- hydroxyindolin-2-one analogs with different substituents on the indole moiety. This X-ray analysis of the title compound was performed to confirm the stereochemistry of the molecule and to obtain detailed information on the conformation of the molecule, which may be useful in structure-activity relationship (SAR) analysis. The title compound was prepared by the aldol condensation of N-phenylindol-2,3-dione (N -phenyl isatin) with 2-amino- 1-methyl-1H-imidazol-4(5H)-one (creatinine) in the presence of sodium acetate in acetic acid under microwave irradiation. The compound was crystallized from ethyl alcohol. This aldol condensation reaction proceeds by the formation of the E-enolate, as per the Zimmerman-Traxler model (Zimmerman & Traxler, 1957), which favores anti products, and leads to the formation of a racemic compound (equimolar RR and SS enantiomers). The molecular structure and the atom-numbering scheme are shown in Fig.1. The isatin ring is planar (r.m.s. deviation = 0.00342 (10) Å) with bond distances and angles comparable with those previously reported for other isatin derivatives (Frolova et al., 1988; Usman, et al., 2002 and Penthala et al. 2009). The indole and creatinine moieties make a dihedral angle of 56.45 (4)°. Intermolecular N—H···O and O—H···N hydrogen bonds stabilize the crystal structure and form a supramolecular aggregation.

Related literature top

For the biological activity of isatin and its derivatives, see: Pandeya et al. (2005). The endogenous oxindoles 5-hydroxyoxindole and isatin are antiproliferative and proapoptotic, see: Cane et al. (2000). For in vitro cytotoxicity evaluation of some substituted isatin derivatives, see: Vine et al. (2007). 2-Indol-3-yl-methylenequinuclidin-3-ols and NADPH oxidase activity has been reported by Sekhar et al. (2003), and novel substituted (Z)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-one and (Z)-(±)-2-(N-benzylindol-3-yl methylene)quinuclidin-3-ol derivatives as potent thermal sensitizing agents by Sonar et al. (2007). For the crystal and molecular structure of isatin, see: Frolova et al. (1988). For the structure of 3-(2-amino-1-methyl-4-oxo-4,5-dihydro-1H-imidazol-5-yl)- 3-hydroxyindolin-2-one monohydrate, see: Penthala et al. (2009) and for 1,1'-diacetyl-3-hydroxy- 2,2',3,3'-tetrahydro-3,3'-bi(1H-indole)-2,2'-dione, see: Usman et al. (2002). The aldol condensation enolate mechanism via a six-membered transition state has been described by Zimmerman & Traxler (1957).

Experimental top

A mixture of N-phenyl isatin (1 mmol), creatinine (1.1 mmol) and sodium acetate (1.2 mmol) in acetic acid (1 ml) was irradiated in a domestic microwave oven for 30 sec with intermittent cooling every 5 sec. The reaction mixture was allowed to cool to room temperature, 10 ml of saturated sodium bicarbonate solution was added and the mixture was stirred for 10 minutes. The precipitate thus obtained was collected by filtration, washed with cold water and dried to afford the crude product. Crystallization from ethyl alcohol gave a white crystalline product of 3-(2-amino-1-methyl-4-oxo-4,5-dihydro-1H- imidazol-5-yl)-3-hydroxy-1-phenylindolin-2-one ethanolate which was suitable for X-ray analysis. ¹H NMR (DMSO-d₆): δ 3.25 (s, 3H), 4.22 (s, 1H), 6.62 (s, 1H, OH), 6.64–6.65 (d, J=2.4 Hz, 1H), 7.00–7.03 (t, J=7.5 Hz, 1H), 7.17–7.23 (m, 2H), 7.44–7.47 (m, 4H), 7.55–7.57 (d, J=7.5 Hz, 1H), 7.60 (bs, 2H, NH₂) p.p.m.; ¹³C NMR (DMSO-d₆): δ 33.02, 70.60, 76.26, 108.92, 122.74, 124.38, 126.95, 127.10, 128.13, 129.60, 129.86, 134.40, 143.93, 171.90, 174.09, 182.53 p.p.m..

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 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.

3-(2-Amino-1-methyl-4-oxo-4,5-dihydro-1H-imidazol-5-yl)-3-hydroxy-1- phenylindolin-2-one ethanol solvate top

Crystal data top

C₁₈H₁₆N₄O₃·C₂H₆O	Z = 2
M_r = 382.42	F(000) = 404
Triclinic, P1	D_x = 1.391 Mg m⁻³
Hall symbol: -P 1	Cu Kα radiation, λ = 1.54178 Å
a = 7.4912 (1) Å	Cell parameters from 9955 reflections
b = 11.0018 (2) Å	θ = 3.8–68.3°
c = 12.0835 (2) Å	µ = 0.82 mm⁻¹
α = 78.152 (1)°	T = 90 K
β = 74.413 (1)°	Block, colourless
γ = 74.090 (1)°	0.11 × 0.11 × 0.08 mm
V = 913.15 (3) Å³

Data collection top

Bruker X8 Proteum diffractometer	3294 independent reflections
Radiation source: fine-focus rotating anode	3126 reflections with I > 2σ(I)
Graded multilayer optics monochromator	R_int = 0.035
Detector resolution: 5.6 pixels mm^-1	θ_max = 68.3°, θ_min = 3.8°
ϕ and ω scans	h = −9→9
Absorption correction: multi-scan (SADABS in APEX2; Bruker, 2006)	k = −13→10
T_min = 0.828, T_max = 0.938	l = −14→14
13576 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)] = 0.037	H-atom parameters constrained
wR(F²) = 0.098	w = 1/[σ^2^(F_o^2^) + (0.0501P)^2^ + 0.3708P] whereP = (F_o^2^ + 2F_c^2^)/3
S = 1.07	(Δ/σ)_max < 0.001
3294 reflections	Δρ_max = 0.37 e Å⁻³
258 parameters	Δρ_min = −0.41 e Å⁻³
0 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: 0.0068 (7)

Crystal data top

C₁₈H₁₆N₄O₃·C₂H₆O	γ = 74.090 (1)°
M_r = 382.42	V = 913.15 (3) Å³
Triclinic, P1	Z = 2
a = 7.4912 (1) Å	Cu Kα radiation
b = 11.0018 (2) Å	µ = 0.82 mm⁻¹
c = 12.0835 (2) Å	T = 90 K
α = 78.152 (1)°	0.11 × 0.11 × 0.08 mm
β = 74.413 (1)°

Data collection top

Bruker X8 Proteum diffractometer	3294 independent reflections
Absorption correction: multi-scan (SADABS in APEX2; Bruker, 2006)	3126 reflections with I > 2σ(I)
T_min = 0.828, T_max = 0.938	R_int = 0.035
13576 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.037	0 restraints
wR(F²) = 0.098	H-atom parameters constrained
S = 1.07	Δρ_max = 0.37 e Å⁻³
3294 reflections	Δρ_min = −0.41 e Å⁻³
258 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 F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ > 2σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ 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
O1	0.37921 (12)	0.08545 (8)	0.23487 (7)	0.0188 (2)
N1	0.16513 (14)	0.24923 (9)	0.32617 (8)	0.0159 (2)
C1	0.29249 (17)	0.19721 (11)	0.23418 (10)	0.0161 (3)
O2	0.50070 (12)	0.30752 (8)	0.07786 (7)	0.0202 (2)
H2	0.5529	0.3158	0.1284	0.030*
N2	0.03753 (14)	0.13607 (10)	0.04645 (8)	0.0174 (2)
C2	0.30826 (17)	0.30455 (11)	0.12863 (10)	0.0173 (3)
O3	−0.10708 (12)	0.31235 (9)	0.14096 (8)	0.0232 (2)
N3	0.26263 (14)	0.00056 (10)	−0.07643 (9)	0.0185 (2)
H3A	0.3780	−0.0201	−0.1202	0.022*
H3B	0.1798	−0.0454	−0.0697	0.022*
C3	0.18841 (17)	0.42116 (12)	0.18239 (10)	0.0178 (3)
N4	0.33379 (14)	0.17486 (10)	−0.02748 (8)	0.0175 (2)
C4	0.15762 (18)	0.54854 (12)	0.13580 (11)	0.0210 (3)
H4	0.2148	0.5746	0.0573	0.025*
C5	0.04026 (19)	0.63828 (12)	0.20688 (11)	0.0222 (3)
H5	0.0180	0.7266	0.1768	0.027*
C6	−0.04402 (18)	0.59920 (12)	0.32105 (11)	0.0212 (3)
H6	−0.1239	0.6615	0.3680	0.025*
C7	−0.01412 (17)	0.47040 (12)	0.36854 (10)	0.0183 (3)
H7	−0.0728	0.4437	0.4465	0.022*
C8	0.10411 (17)	0.38371 (11)	0.29745 (10)	0.0168 (3)
C9	0.12524 (17)	0.18231 (11)	0.44190 (10)	0.0161 (3)
C10	0.27258 (18)	0.12805 (11)	0.49893 (11)	0.0192 (3)
H10	0.3994	0.1339	0.4615	0.023*
C11	0.2316 (2)	0.06493 (12)	0.61182 (11)	0.0233 (3)
H11	0.3312	0.0268	0.6516	0.028*
C12	0.0459 (2)	0.05757 (12)	0.66629 (11)	0.0247 (3)
H12	0.0185	0.0150	0.7435	0.030*
C13	−0.10000 (19)	0.11217 (12)	0.60827 (11)	0.0233 (3)
H13	−0.2271	0.1071	0.6460	0.028*
C14	−0.06071 (18)	0.17416 (12)	0.49517 (11)	0.0195 (3)
H14	−0.1599	0.2105	0.4548	0.023*
C15	0.22403 (17)	0.28338 (11)	0.03230 (10)	0.0173 (3)
H15	0.2094	0.3626	−0.0256	0.021*
C16	0.03012 (17)	0.24701 (12)	0.08034 (10)	0.0175 (3)
C17	0.21402 (17)	0.09987 (11)	−0.02122 (10)	0.0162 (3)
C18	0.49912 (18)	0.18208 (12)	−0.12386 (10)	0.0207 (3)
H18A	0.5813	0.0964	−0.1304	0.031*
H18B	0.5707	0.2375	−0.1096	0.031*
H18C	0.4562	0.2172	−0.1962	0.031*
O1S	0.57472 (13)	0.29564 (10)	0.30873 (9)	0.0304 (3)
H1S	0.6853	0.2952	0.2685	0.046*
C1S	0.5142 (2)	0.39650 (15)	0.37674 (14)	0.0336 (3)
H1S1	0.5991	0.3811	0.4309	0.040*
H1S2	0.3837	0.3965	0.4237	0.040*
C2S	0.5151 (2)	0.52356 (16)	0.30585 (16)	0.0413 (4)
H2S1	0.6444	0.5248	0.2601	0.062*
H2S2	0.4729	0.5894	0.3570	0.062*
H2S3	0.4285	0.5405	0.2535	0.062*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0220 (4)	0.0146 (4)	0.0180 (4)	−0.0041 (3)	−0.0011 (3)	−0.0034 (3)
N1	0.0206 (5)	0.0124 (5)	0.0138 (5)	−0.0041 (4)	−0.0026 (4)	−0.0012 (4)
C1	0.0187 (6)	0.0160 (6)	0.0152 (6)	−0.0067 (5)	−0.0032 (5)	−0.0030 (4)
O2	0.0216 (5)	0.0249 (5)	0.0171 (4)	−0.0115 (4)	−0.0028 (3)	−0.0033 (3)
N2	0.0185 (5)	0.0188 (5)	0.0149 (5)	−0.0057 (4)	−0.0020 (4)	−0.0028 (4)
C2	0.0216 (6)	0.0160 (6)	0.0145 (6)	−0.0076 (5)	−0.0020 (5)	−0.0016 (5)
O3	0.0225 (5)	0.0246 (5)	0.0212 (5)	−0.0051 (4)	0.0000 (4)	−0.0080 (4)
N3	0.0177 (5)	0.0193 (5)	0.0199 (5)	−0.0067 (4)	−0.0011 (4)	−0.0068 (4)
C3	0.0231 (6)	0.0168 (6)	0.0160 (6)	−0.0068 (5)	−0.0061 (5)	−0.0026 (5)
N4	0.0191 (5)	0.0193 (5)	0.0151 (5)	−0.0075 (4)	0.0000 (4)	−0.0056 (4)
C4	0.0289 (7)	0.0183 (6)	0.0182 (6)	−0.0084 (5)	−0.0086 (5)	0.0002 (5)
C5	0.0306 (7)	0.0136 (6)	0.0253 (7)	−0.0054 (5)	−0.0126 (5)	−0.0003 (5)
C6	0.0253 (6)	0.0173 (6)	0.0234 (6)	−0.0017 (5)	−0.0096 (5)	−0.0068 (5)
C7	0.0220 (6)	0.0179 (6)	0.0165 (6)	−0.0048 (5)	−0.0061 (5)	−0.0033 (5)
C8	0.0215 (6)	0.0140 (6)	0.0173 (6)	−0.0058 (5)	−0.0071 (5)	−0.0017 (4)
C9	0.0236 (6)	0.0110 (5)	0.0131 (6)	−0.0043 (4)	−0.0017 (5)	−0.0028 (4)
C10	0.0230 (6)	0.0150 (6)	0.0188 (6)	−0.0033 (5)	−0.0032 (5)	−0.0042 (5)
C11	0.0337 (7)	0.0156 (6)	0.0194 (6)	−0.0009 (5)	−0.0089 (5)	−0.0024 (5)
C12	0.0409 (8)	0.0152 (6)	0.0154 (6)	−0.0078 (5)	−0.0014 (5)	−0.0011 (5)
C13	0.0280 (7)	0.0191 (6)	0.0206 (6)	−0.0099 (5)	0.0044 (5)	−0.0053 (5)
C14	0.0221 (6)	0.0162 (6)	0.0203 (6)	−0.0047 (5)	−0.0032 (5)	−0.0043 (5)
C15	0.0216 (6)	0.0165 (6)	0.0140 (6)	−0.0060 (5)	−0.0023 (5)	−0.0029 (4)
C16	0.0201 (6)	0.0190 (6)	0.0130 (5)	−0.0053 (5)	−0.0032 (5)	−0.0014 (4)
C17	0.0186 (6)	0.0179 (6)	0.0126 (5)	−0.0056 (5)	−0.0039 (4)	−0.0005 (4)
C18	0.0218 (6)	0.0246 (6)	0.0164 (6)	−0.0099 (5)	0.0011 (5)	−0.0054 (5)
O1S	0.0213 (5)	0.0303 (5)	0.0384 (6)	−0.0077 (4)	−0.0007 (4)	−0.0078 (4)
C1S	0.0254 (7)	0.0339 (8)	0.0426 (9)	−0.0049 (6)	−0.0067 (6)	−0.0115 (7)
C2S	0.0424 (9)	0.0358 (9)	0.0530 (10)	−0.0102 (7)	−0.0231 (8)	−0.0044 (7)

Geometric parameters (Å, º) top

O1—C1	1.2226 (15)	C7—C8	1.3770 (17)
N1—C1	1.3658 (15)	C7—H7	0.9500
N1—C8	1.4220 (15)	C9—C14	1.3876 (18)
N1—C9	1.4353 (15)	C9—C10	1.3886 (18)
C1—C2	1.5531 (16)	C10—C11	1.3929 (18)
O2—C2	1.4136 (15)	C10—H10	0.9500
O2—H2	0.8400	C11—C12	1.386 (2)
N2—C16	1.3477 (16)	C11—H11	0.9500
N2—C17	1.3562 (15)	C12—C13	1.388 (2)
C2—C3	1.5071 (17)	C12—H12	0.9500
C2—C15	1.5472 (16)	C13—C14	1.3895 (18)
O3—C16	1.2314 (15)	C13—H13	0.9500
N3—C17	1.3123 (16)	C14—H14	0.9500
N3—H3A	0.8800	C15—C16	1.5419 (17)
N3—H3B	0.8800	C15—H15	1.0000
C3—C4	1.3794 (17)	C18—H18A	0.9800
C3—C8	1.3918 (17)	C18—H18B	0.9800
N4—C17	1.3546 (16)	C18—H18C	0.9800
N4—C15	1.4560 (15)	O1S—C1S	1.4181 (18)
N4—C18	1.4621 (15)	O1S—H1S	0.8400
C4—C5	1.3972 (18)	C1S—C2S	1.483 (2)
C4—H4	0.9500	C1S—H1S1	0.9900
C5—C6	1.3870 (19)	C1S—H1S2	0.9900
C5—H5	0.9500	C2S—H2S1	0.9800
C6—C7	1.3960 (18)	C2S—H2S2	0.9800
C6—H6	0.9500	C2S—H2S3	0.9800

C1—N1—C8	110.74 (10)	C12—C11—C10	120.23 (12)
C1—N1—C9	124.57 (10)	C12—C11—H11	119.9
C8—N1—C9	123.74 (10)	C10—C11—H11	119.9
O1—C1—N1	125.87 (11)	C11—C12—C13	120.17 (12)
O1—C1—C2	125.91 (10)	C11—C12—H12	119.9
N1—C1—C2	108.21 (10)	C13—C12—H12	119.9
C2—O2—H2	109.5	C12—C13—C14	120.17 (12)
C16—N2—C17	106.75 (10)	C12—C13—H13	119.9
O2—C2—C3	115.27 (10)	C14—C13—H13	119.9
O2—C2—C15	106.63 (9)	C9—C14—C13	119.20 (12)
C3—C2—C15	110.59 (10)	C9—C14—H14	120.4
O2—C2—C1	111.04 (9)	C13—C14—H14	120.4
C3—C2—C1	101.86 (9)	N4—C15—C16	100.87 (9)
C15—C2—C1	111.52 (9)	N4—C15—C2	114.64 (10)
C17—N3—H3A	120.0	C16—C15—C2	112.68 (9)
C17—N3—H3B	120.0	N4—C15—H15	109.4
H3A—N3—H3B	120.0	C16—C15—H15	109.4
C4—C3—C8	120.49 (11)	C2—C15—H15	109.4
C4—C3—C2	130.40 (11)	O3—C16—N2	127.04 (11)
C8—C3—C2	109.10 (10)	O3—C16—C15	123.08 (11)
C17—N4—C15	107.56 (10)	N2—C16—C15	109.88 (10)
C17—N4—C18	122.36 (10)	N3—C17—N4	123.26 (11)
C15—N4—C18	122.80 (10)	N3—C17—N2	122.16 (11)
C3—C4—C5	118.36 (11)	N4—C17—N2	114.58 (10)
C3—C4—H4	120.8	N4—C18—H18A	109.5
C5—C4—H4	120.8	N4—C18—H18B	109.5
C6—C5—C4	120.40 (11)	H18A—C18—H18B	109.5
C6—C5—H5	119.8	N4—C18—H18C	109.5
C4—C5—H5	119.8	H18A—C18—H18C	109.5
C5—C6—C7	121.51 (12)	H18B—C18—H18C	109.5
C5—C6—H6	119.2	C1S—O1S—H1S	109.5
C7—C6—H6	119.2	O1S—C1S—C2S	112.92 (14)
C8—C7—C6	117.14 (11)	O1S—C1S—H1S1	109.0
C8—C7—H7	121.4	C2S—C1S—H1S1	109.0
C6—C7—H7	121.4	O1S—C1S—H1S2	109.0
C7—C8—C3	122.10 (11)	C2S—C1S—H1S2	109.0
C7—C8—N1	128.13 (11)	H1S1—C1S—H1S2	107.8
C3—C8—N1	109.73 (10)	C1S—C2S—H2S1	109.5
C14—C9—C10	121.20 (11)	C1S—C2S—H2S2	109.5
C14—C9—N1	119.23 (11)	H2S1—C2S—H2S2	109.5
C10—C9—N1	119.56 (11)	C1S—C2S—H2S3	109.5
C9—C10—C11	119.02 (12)	H2S1—C2S—H2S3	109.5
C9—C10—H10	120.5	H2S2—C2S—H2S3	109.5
C11—C10—H10	120.5

C8—N1—C1—O1	174.88 (11)	C1—N1—C9—C10	57.36 (16)
C9—N1—C1—O1	5.70 (19)	C8—N1—C9—C10	−110.45 (13)
C8—N1—C1—C2	−5.06 (13)	C14—C9—C10—C11	−0.27 (18)
C9—N1—C1—C2	−174.24 (10)	N1—C9—C10—C11	179.09 (10)
O1—C1—C2—O2	−50.77 (15)	C9—C10—C11—C12	−0.49 (18)
N1—C1—C2—O2	129.18 (10)	C10—C11—C12—C13	0.53 (19)
O1—C1—C2—C3	−174.02 (12)	C11—C12—C13—C14	0.19 (19)
N1—C1—C2—C3	5.93 (12)	C10—C9—C14—C13	0.99 (18)
O1—C1—C2—C15	68.01 (15)	N1—C9—C14—C13	−178.38 (11)
N1—C1—C2—C15	−112.05 (11)	C12—C13—C14—C9	−0.94 (18)
O2—C2—C3—C4	53.97 (17)	C17—N4—C15—C16	4.68 (12)
C15—C2—C3—C4	−67.06 (16)	C18—N4—C15—C16	155.35 (10)
C1—C2—C3—C4	174.30 (13)	C17—N4—C15—C2	126.01 (10)
O2—C2—C3—C8	−125.10 (11)	C18—N4—C15—C2	−83.31 (13)
C15—C2—C3—C8	113.87 (11)	O2—C2—C15—N4	52.11 (12)
C1—C2—C3—C8	−4.77 (12)	C3—C2—C15—N4	178.14 (9)
C8—C3—C4—C5	0.01 (18)	C1—C2—C15—N4	−69.27 (13)
C2—C3—C4—C5	−178.97 (12)	O2—C2—C15—C16	166.73 (9)
C3—C4—C5—C6	−0.60 (19)	C3—C2—C15—C16	−67.24 (13)
C4—C5—C6—C7	0.32 (19)	C1—C2—C15—C16	45.36 (13)
C5—C6—C7—C8	0.56 (18)	C17—N2—C16—O3	178.51 (12)
C6—C7—C8—C3	−1.17 (18)	C17—N2—C16—C15	−1.87 (13)
C6—C7—C8—N1	176.39 (11)	N4—C15—C16—O3	177.90 (11)
C4—C3—C8—C7	0.91 (19)	C2—C15—C16—O3	55.19 (15)
C2—C3—C8—C7	−179.91 (11)	N4—C15—C16—N2	−1.74 (12)
C4—C3—C8—N1	−177.05 (11)	C2—C15—C16—N2	−124.45 (11)
C2—C3—C8—N1	2.13 (14)	C15—N4—C17—N3	172.92 (11)
C1—N1—C8—C7	−175.84 (12)	C18—N4—C17—N3	22.09 (18)
C9—N1—C8—C7	−6.55 (19)	C15—N4—C17—N2	−6.58 (13)
C1—N1—C8—C3	1.96 (14)	C18—N4—C17—N2	−157.41 (11)
C9—N1—C8—C3	171.25 (11)	C16—N2—C17—N3	−174.16 (11)
C1—N1—C9—C14	−123.26 (13)	C16—N2—C17—N4	5.35 (14)
C8—N1—C9—C14	68.92 (15)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O1S	0.84	2.19	2.9579 (14)	152
O2—H2···O3ⁱ	0.84	2.58	3.2440 (12)	137
N3—H3A···O1ⁱⁱ	0.88	2.02	2.8898 (13)	169
N3—H3B···N2ⁱⁱⁱ	0.88	2.06	2.9391 (15)	174
O1S—H1S···O3ⁱ	0.84	1.89	2.7048 (13)	162

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

Experimental details

Crystal data
Chemical formula	C₁₈H₁₆N₄O₃·C₂H₆O
M_r	382.42
Crystal system, space group	Triclinic, P1
Temperature (K)	90
a, b, c (Å)	7.4912 (1), 11.0018 (2), 12.0835 (2)
α, β, γ (°)	78.152 (1), 74.413 (1), 74.090 (1)
V (Å³)	913.15 (3)
Z	2
Radiation type	Cu Kα
µ (mm⁻¹)	0.82
Crystal size (mm)	0.11 × 0.11 × 0.08

Data collection
Diffractometer	Bruker X8 Proteum diffractometer
Absorption correction	Multi-scan (SADABS in APEX2; Bruker, 2006)
T_min, T_max	0.828, 0.938
No. of measured, independent and observed [I > 2σ(I)] reflections	13576, 3294, 3126
R_int	0.035
(sin θ/λ)_max (Å⁻¹)	0.602

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.037, 0.098, 1.07
No. of reflections	3294
No. of parameters	258
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.37, −0.41

Computer programs: APEX2 (Bruker, 2006), SAINT (Bruker, 2006), 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
O2—H2···O1S	0.84	2.19	2.9579 (14)	152.0
O2—H2···O3ⁱ	0.84	2.58	3.2440 (12)	136.6
N3—H3A···O1ⁱⁱ	0.88	2.02	2.8898 (13)	169.3
N3—H3B···N2ⁱⁱⁱ	0.88	2.06	2.9391 (15)	173.5
O1S—H1S···O3ⁱ	0.84	1.89	2.7048 (13)	162.3

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

Acknowledgements

This investigation was supported by NIH/National Cancer Institute grant PO1 CA104457 (PAC) and by NSF MRI grant CHE 0319176 (SP).

References

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Volume 65| Part 10| October 2009| Pages o2439-o2440

doi:10.1107/S1600536809033881

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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

3-(2-Amino-1-methyl-4-oxo-4,5-di­hydro-1H-imidazol-5-yl)-3-hydr­­oxy-1-phenyl­indolin-2-one ethanol solvate

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Experimental

Crystal data

Data collection

Refinement

Supporting information

Acknowledgements

References

organic compounds

3-(2-Amino-1-methyl-4-oxo-4,5-dihydro-1H-imidazol-5-yl)-3-hydroxy-1-phenylindolin-2-one ethanol solvate