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

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 65| Part 11| November 2009| Pages o2909-o2910
https://doi.org/10.1107/S1600536809043797

3-(2-Amino-1-methyl-4-oxo-4,5-di­hydro-1H-imidazol-5-yl)-5-fluoro-3-hydr­­oxy-1-methyl­indolin-2-one methanol hemisolvate

Narsimha Reddy Penthala,a Thirupathi Reddy Yerram Reddy,a Sean Parkinb and Peter A. Crooksa*

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 22 October 2009; online 31 October 2009)

In the title compound, C13H13FN4O3·0.5CH3OH, mol­ecules are packed in the crystal structure by a series of O—H⋯N, N—H⋯O, N—H⋯F and O—H⋯O inter­molecular hydrogen bonds. The indole and creatinine units make a dihedral angle of 60.80 (4)°.

Related literature

For the biological activity of isatin and its derivatives, see: Pandeya et al. (2005[Pandeya, S. N., Smitha, S., Jyoti, M. & Sridhar, S. K. (2005). Acta Pharm. 55, 27-46.]); The endogenous oxindoles 5-hydroxy­oxindole and isatin are anti­proliferative and proapoptotic, see: Cane et al. (2000[Cane, A., Tournaire, M. C., Barritault, D. & Crumeyrolle-Arias, M. (2000). Biochem. Biophys. Res. Commun. 276, 379-384.]). For the in vitro cytotoxicity evaluation of some substituted isatin derivatives, see: Vine et al. (2007[Vine, K. L., Locke, J. M., Ranson, M., Benkendorff, K., Pyne, S. G. & Bremner, J. B. (2007). Bioorg. Med. Chem. 15, 931-938.]). For 2-indol-3-yl-methyl­enequinuclidin-3-ols and NADPH oxidase activity, see: Sekhar et al. (2003[Sekhar, K. R., Crooks, P. A., Sonar, V. N., Friedman, D. B., Chan, J. Y., Meredith, M. J., Starnes, J. H., Kelton, K. R., Summar, S. R., Sasi, S. & Freeman, M. L. (2003). Cancer Res. 63, 5636-5645.]) and for 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, see: Sonar et al. (2007[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.]). For the crystal and mol­ecular structure of isatin, see: Frolova et al. (1988[Frolova, N. A., Kravtsov, V. Kh., Biyushkin, V. N., Chumakov, Yu. M., Bel'kova, O. N. & Malinovskii, T. I. (1988). J. Struct. Chem. 29, 491-493.]), for 3-(2-amino-1-methyl-4-oxo-4,5-dihydro-1H-imidazol-5-yl)-3-hydroxy­indolin-2-one monohydrate, see: Penthala et al. (2009[Penthala, N. R., Reddy, T. R. Y., Parkin, S. & Crooks, P. A. (2009). Acta Cryst. E65, o552.]) 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[Usman, A., Razak, I. A., Fun, H.-K., Chantrapromma, S., Zhao, B.-G. & Xu, J.-H. (2002). Acta Cryst. C58, o24-o25.]). For the aldol condensation enolate mechanism via a six-membered transition state, see: Zimmerman & Traxler (1957[Zimmerman, H. E. & Traxler, M. D. (1957). J. Am. Chem. Soc. 79, 1920-1923.]).

[Scheme 1]

Experimental

Crystal data

  • C13H13FN4O3·0.5CH4O

  • Mr = 308.30

  • Monoclinic, I 2/a

  • a = 14.3088 (3) Å

  • b = 10.7900 (2) Å

  • c = 18.1286 (5) Å

  • β = 107.676 (1)°

  • V = 2666.77 (10) Å3

  • Z = 8

  • Cu Kα radiation

  • μ = 1.04 mm−1

  • T = 90 K

  • 0.15 × 0.03 × 0.02 mm
Data collection

  • Bruker X8 Proteum diffractometer

  • Absorption correction: multi-scan (SADABS in APEX2; Bruker, 2006[Bruker (2006). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.805, Tmax = 0.979

  • 19606 measured reflections

  • 2448 independent reflections

  • 2196 reflections with I > 2σ(I)

  • Rint = 0.041
Refinement

  • R[F2 > 2σ(F2)] = 0.035

  • wR(F2) = 0.092

  • S = 1.04

  • 2448 reflections

  • 211 parameters

  • H-atom parameters constrained

  • Δρmax = 0.25 e Å−3

  • Δρmin = −0.27 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A
O2—H2⋯N2i 0.84 1.97 2.8074 (16) 171
N3—H3A⋯O3ii 0.88 2.25 3.1265 (16) 177
N3—H3B⋯O1iii 0.88 2.12 2.8490 (17) 140
N3—H3B⋯F1iv 0.88 2.45 2.8743 (14) 110
O1S—H1S4⋯O3 0.84 2.01 2.846 (3) 171
Symmetry codes: (i) [-x+1, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]; (ii) [x+{\script{1\over 2}}, -y+1, z]; (iii) [-x+1, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]; (iv) [-x+{\script{3\over 2}}, -y+{\script{3\over 2}}, -z+{\script{1\over 2}}].

Data collection: APEX2 (Bruker, 2006[Bruker (2006). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2006[Bruker (2006). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: XP in SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXL97 and local procedures.

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S1600536809043797/hg2556sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536809043797/hg2556Isup2.hkl

checkCIF report


Comment top

Isatin analogs display diverse biological activities, (Pandeya et al., 2005; Cane et al., 2000 and Vine et al., 2007). In continuation of our work on radiosensitizers (Sekhar et al., 2003; Sonar et al., 2007), we focused on 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. The main aim of X-ray analysis of the title compound was to confirm the stereochemistry of the molecule and to obtain detailed information on the structural conformation, which may be useful in structure-activity relationship (SAR) analysis. The title compound was prepared by the aldol condensation of 5-fluoro-N-methyl indol-2,3-dione 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 methyl alcohol. This aldol condensation reaction proceeds by the formation of the E-enolate, as per the Zimmerman-Traxler model (Zimmerman & Traxler, 1957). The molecular structure and the atom-numbering scheme are shown in Fig.1. The isatin ring is planar with r.m.s. deviation of 0.0232 (11) Å and the creatinine ring has r.m.s. deviation of 0.0307 (8) 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 60.80 (4) °. Intermolecular O—H···N, N—H···O, N—H···F and O—H···O 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 the in vitro cytotoxicity evaluation of some substituted isatin derivatives, see: Vine et al. (2007). 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-yl methylene)quinuclidin-3-ol derivatives as potent thermal sensitizing agents, see: Sonar et al. (2007). For the crystal and molecular structure of isatin, see: Frolova et al. (1988), for 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). For the aldol condensation enolate mechanism via a six-membered transition state, see: Zimmerman & Traxler (1957).

Experimental top

A mixture of 5-fluoro-N-methyl 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 methyl alcohol gave a white crystalline product of 3-(2-amino-1-methyl-4-oxo-4,5-dihydro-1H-imidazol-5-yl)- 5-fluoro-3-hydroxy-1-methylindolin-2-one methanolate, which was suitable for X-ray analysis. 1H NMR (DMSO-d6): δ 3.05 (s, 3H), 3.18 (s, 3H), 4.11 (s, 1H), 6.58 (s, 1H, OH), 6.85–6.89 (dd, J=2.7 Hz, J=5.4 Hz, 1H), 6.93–6.97 (dd, J=2.7 Hz, J=4.2 Hz, 1H), 7.11–7.18 (m, 1H), 7.42 (bs, 1H, NH), 7.72 (bs, 1H, NH), p.p.m.; 13C NMR (DMSO-d6): δ 26.08, 32.76, 48.62, 69.87, 76.29, 109.14, 109.25, 111.16, 111.50, 115.42, 115.72, 128.84, 128.95, 140.23, 156.35, 159.49, 171.98, 173.97, 181.85 p.p.m..

Refinement top

H atoms were found in difference Fourier maps and subsequently placed in idealized positions with constrained distances of 0.98Å (RCH3), 1.00 Å (R3CH), 0.95 Å (CArH), 0.84 Å (O—H), 0.88 Å (N—H), and with Uiso(H) values set to either 1.2Ueq or 1.5Ueq (RCH3, OH) of the attached atom.

The presence of difference map peaks in the vicinity of the 2-fold axis at ca (1/4,0.62,0) were consistent with a disordered methanol solvent molecule. This methanol was modelled at half occupancy, such that application of the 2-fold site symmetry generates a full occupancy for the site. There is an O—H···O hydrogen-bonding interaction between this methanol and O3 of the main molecule (see Table 1).

Structure description top

Isatin analogs display diverse biological activities, (Pandeya et al., 2005; Cane et al., 2000 and Vine et al., 2007). In continuation of our work on radiosensitizers (Sekhar et al., 2003; Sonar et al., 2007), we focused on 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. The main aim of X-ray analysis of the title compound was to confirm the stereochemistry of the molecule and to obtain detailed information on the structural conformation, which may be useful in structure-activity relationship (SAR) analysis. The title compound was prepared by the aldol condensation of 5-fluoro-N-methyl indol-2,3-dione 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 methyl alcohol. This aldol condensation reaction proceeds by the formation of the E-enolate, as per the Zimmerman-Traxler model (Zimmerman & Traxler, 1957). The molecular structure and the atom-numbering scheme are shown in Fig.1. The isatin ring is planar with r.m.s. deviation of 0.0232 (11) Å and the creatinine ring has r.m.s. deviation of 0.0307 (8) 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 60.80 (4) °. Intermolecular O—H···N, N—H···O, N—H···F and O—H···O hydrogen bonds stabilize the crystal structure and form a supramolecular aggregation.

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 the in vitro cytotoxicity evaluation of some substituted isatin derivatives, see: Vine et al. (2007). 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-yl methylene)quinuclidin-3-ol derivatives as potent thermal sensitizing agents, see: Sonar et al. (2007). For the crystal and molecular structure of isatin, see: Frolova et al. (1988), for 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). For the aldol condensation enolate mechanism via a six-membered transition state, see: Zimmerman & Traxler (1957).

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
[Figure 1] 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)- 5-fluoro-3-hydroxy-1-methylindolin-2-one methanol hemisolvate top
Crystal data top
C13H13FN4O3·0.5CH4OF(000) = 1288
Mr = 308.30Dx = 1.536 Mg m−3
Monoclinic, I2/aCu Kα radiation, λ = 1.54178 Å
Hall symbol: -I 2yaCell parameters from 9961 reflections
a = 14.3088 (3) Åθ = 4.8–68.5°
b = 10.7900 (2) ŵ = 1.04 mm−1
c = 18.1286 (5) ÅT = 90 K
β = 107.676 (1)°Rod, colourless
V = 2666.77 (10) Å30.15 × 0.03 × 0.02 mm
Z = 8
Data collection top
Bruker X8 Proteum
diffractometer		2448 independent reflections
Radiation source: fine-focus rotating anode2196 reflections with I > 2σ(I)
Graded multilayer optics monochromatorRint = 0.041
Detector resolution: 5.6 pixels mm-1θmax = 68.5°, θmin = 4.8°
φ and ω scansh = −17→17
Absorption correction: multi-scan
(SADABS in APEX2; Bruker, 2006)		k = −13→13
Tmin = 0.805, Tmax = 0.979l = −17→21
19606 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.035Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.092H-atom parameters constrained
S = 1.04 w = 1/[σ2(Fo2) + (0.0452P)2 + 3.1985P]
where P = (Fo2 + 2Fc2)/3
2448 reflections(Δ/σ)max < 0.001
211 parametersΔρmax = 0.25 e Å−3
0 restraintsΔρmin = −0.27 e Å−3
Crystal data top
C13H13FN4O3·0.5CH4OV = 2666.77 (10) Å3
Mr = 308.30Z = 8
Monoclinic, I2/aCu Kα radiation
a = 14.3088 (3) ŵ = 1.04 mm−1
b = 10.7900 (2) ÅT = 90 K
c = 18.1286 (5) Å0.15 × 0.03 × 0.02 mm
β = 107.676 (1)°
Data collection top
Bruker X8 Proteum
diffractometer		2448 independent reflections
Absorption correction: multi-scan
(SADABS in APEX2; Bruker, 2006)		2196 reflections with I > 2σ(I)
Tmin = 0.805, Tmax = 0.979Rint = 0.041
19606 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0350 restraints
wR(F2) = 0.092H-atom parameters constrained
S = 1.04Δρmax = 0.25 e Å−3
2448 reflectionsΔρmin = −0.27 e Å−3
211 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
xyzUiso*/UeqOcc. (<1)
F10.71683 (6)0.82226 (8)0.40909 (5)0.0226 (2)
O10.34944 (7)0.34900 (10)0.34227 (6)0.0220 (2)
N10.40050 (8)0.53388 (11)0.40330 (7)0.0180 (3)
C10.40738 (10)0.43524 (13)0.35922 (8)0.0171 (3)
O20.56972 (7)0.35213 (9)0.37870 (6)0.0182 (2)
H20.54650.28220.36280.027*
N20.48670 (8)0.61111 (11)0.17484 (7)0.0186 (3)
C20.50466 (10)0.44565 (13)0.33829 (8)0.0164 (3)
O30.34268 (7)0.56370 (9)0.20215 (6)0.0207 (2)
N30.64656 (9)0.58544 (12)0.16571 (8)0.0230 (3)
H3A0.70060.54110.17620.028*
H3B0.64170.65490.13930.028*
C30.54173 (10)0.57182 (13)0.37146 (8)0.0162 (3)
N40.57662 (8)0.44285 (11)0.22994 (7)0.0168 (3)
C40.62309 (10)0.64045 (13)0.37024 (8)0.0168 (3)
H40.66680.61220.34360.020*
C50.63765 (10)0.75245 (14)0.40985 (8)0.0181 (3)
C60.57663 (11)0.79772 (14)0.44928 (8)0.0205 (3)
H60.59040.87470.47580.025*
C70.49419 (11)0.72920 (14)0.44984 (8)0.0206 (3)
H70.45030.75820.47620.025*
C80.47874 (10)0.61742 (13)0.41062 (8)0.0174 (3)
C90.32581 (11)0.54673 (15)0.44237 (9)0.0227 (3)
H9A0.27150.59710.41050.034*
H9B0.35440.58720.49260.034*
H9C0.30130.46460.45030.034*
C100.48606 (10)0.43188 (13)0.25013 (8)0.0158 (3)
H100.45210.35190.23080.019*
C110.42843 (10)0.54179 (13)0.20572 (8)0.0166 (3)
C120.57275 (10)0.54783 (13)0.18962 (8)0.0174 (3)
C130.65283 (10)0.34938 (13)0.24071 (9)0.0200 (3)
H13A0.66060.32760.19040.030*
H13B0.63440.27530.26440.030*
H13C0.71490.38220.27460.030*
O1S0.2149 (2)0.6430 (4)0.05671 (19)0.0769 (13)0.50
H1S40.25740.62390.09840.115*0.50
C1S0.2489 (9)0.6226 (3)−0.0003 (6)0.0403 (9)0.5
H1S10.31210.66490.00910.060*0.50
H2S10.20260.6540−0.04820.060*0.50
H3S10.25800.5332−0.00510.060*0.50
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
F10.0206 (4)0.0228 (5)0.0262 (5)−0.0075 (3)0.0100 (3)−0.0027 (3)
O10.0189 (5)0.0224 (5)0.0266 (6)−0.0049 (4)0.0098 (4)−0.0021 (4)
N10.0153 (6)0.0215 (6)0.0188 (6)−0.0016 (5)0.0076 (5)−0.0022 (5)
C10.0156 (7)0.0204 (7)0.0158 (7)0.0003 (5)0.0056 (5)0.0016 (5)
O20.0172 (5)0.0165 (5)0.0200 (5)0.0007 (4)0.0043 (4)0.0002 (4)
N20.0174 (6)0.0192 (6)0.0203 (6)0.0003 (5)0.0073 (5)0.0020 (5)
C20.0138 (6)0.0176 (7)0.0180 (7)−0.0001 (5)0.0052 (5)0.0006 (5)
O30.0153 (5)0.0223 (5)0.0246 (5)0.0007 (4)0.0065 (4)0.0000 (4)
N30.0202 (6)0.0225 (6)0.0297 (7)0.0015 (5)0.0129 (5)0.0070 (5)
C30.0160 (7)0.0175 (7)0.0145 (6)0.0016 (5)0.0039 (5)0.0012 (5)
N40.0158 (6)0.0166 (6)0.0206 (6)0.0013 (4)0.0096 (5)0.0014 (5)
C40.0152 (6)0.0196 (7)0.0158 (7)0.0008 (5)0.0050 (5)0.0004 (5)
C50.0158 (6)0.0197 (7)0.0180 (7)−0.0029 (5)0.0037 (5)0.0029 (5)
C60.0231 (7)0.0192 (7)0.0184 (7)−0.0004 (6)0.0051 (6)−0.0032 (6)
C70.0199 (7)0.0241 (7)0.0190 (7)0.0013 (6)0.0078 (6)−0.0028 (6)
C80.0147 (6)0.0211 (7)0.0160 (7)0.0000 (5)0.0039 (5)0.0012 (5)
C90.0184 (7)0.0321 (8)0.0206 (7)−0.0025 (6)0.0103 (6)−0.0039 (6)
C100.0133 (7)0.0168 (7)0.0185 (7)−0.0015 (5)0.0069 (5)−0.0010 (5)
C110.0160 (7)0.0176 (7)0.0160 (7)−0.0003 (5)0.0044 (5)−0.0027 (5)
C120.0181 (7)0.0184 (7)0.0160 (7)−0.0015 (5)0.0058 (5)−0.0016 (5)
C130.0183 (7)0.0197 (7)0.0245 (7)0.0034 (6)0.0102 (6)0.0008 (6)
O1S0.0548 (19)0.136 (4)0.0458 (18)0.060 (2)0.0247 (16)0.038 (2)
C1S0.0351 (15)0.0419 (18)0.0384 (17)0.012 (4)0.0029 (13)−0.033 (4)
Geometric parameters (Å, º) top
F1—C51.3641 (16)C4—C51.389 (2)
O1—C11.2220 (17)C4—H40.9500
N1—C11.3525 (19)C5—C61.375 (2)
N1—C81.4117 (18)C6—C71.395 (2)
N1—C91.4570 (18)C6—H60.9500
C1—C21.5539 (19)C7—C81.383 (2)
O2—C21.4168 (16)C7—H70.9500
O2—H20.8400C9—H9A0.9800
N2—C111.3606 (18)C9—H9B0.9800
N2—C121.3615 (18)C9—H9C0.9800
C2—C31.5175 (19)C10—C111.5270 (19)
C2—C101.546 (2)C10—H101.0000
O3—C111.2318 (17)C13—H13A0.9800
N3—C121.3214 (19)C13—H13B0.9800
N3—H3A0.8800C13—H13C0.9800
N3—H3B0.8800O1S—C1S1.288 (10)
C3—C41.386 (2)O1S—H1S40.8400
C3—C81.395 (2)C1S—H1S10.9800
N4—C121.3401 (19)C1S—H2S10.9800
N4—C131.4543 (18)C1S—H3S10.9800
N4—C101.4544 (17)
C1—N1—C8111.10 (12)C7—C8—C3122.81 (13)
C1—N1—C9123.91 (12)C7—C8—N1127.11 (13)
C8—N1—C9124.85 (12)C3—C8—N1110.08 (12)
O1—C1—N1125.61 (13)N1—C9—H9A109.5
O1—C1—C2125.69 (13)N1—C9—H9B109.5
N1—C1—C2108.59 (11)H9A—C9—H9B109.5
C2—O2—H2109.5N1—C9—H9C109.5
C11—N2—C12105.90 (12)H9A—C9—H9C109.5
O2—C2—C3109.77 (11)H9B—C9—H9C109.5
O2—C2—C10110.25 (11)N4—C10—C11100.60 (11)
C3—C2—C10115.20 (11)N4—C10—C2111.45 (11)
O2—C2—C1108.60 (11)C11—C10—C2111.49 (11)
C3—C2—C1101.49 (11)N4—C10—H10111.0
C10—C2—C1111.09 (11)C11—C10—H10111.0
C12—N3—H3A120.0C2—C10—H10111.0
C12—N3—H3B120.0O3—C11—N2126.72 (13)
H3A—N3—H3B120.0O3—C11—C10123.14 (13)
C4—C3—C8119.69 (13)N2—C11—C10110.09 (11)
C4—C3—C2131.87 (13)N3—C12—N4122.26 (13)
C8—C3—C2108.42 (12)N3—C12—N2123.14 (13)
C12—N4—C13124.37 (12)N4—C12—N2114.60 (12)
C12—N4—C10108.28 (11)N4—C13—H13A109.5
C13—N4—C10126.78 (11)N4—C13—H13B109.5
C3—C4—C5116.85 (13)H13A—C13—H13B109.5
C3—C4—H4121.6N4—C13—H13C109.5
C5—C4—H4121.6H13A—C13—H13C109.5
F1—C5—C6118.00 (13)H13B—C13—H13C109.5
F1—C5—C4118.03 (12)C1S—O1S—H1S4109.5
C6—C5—C4123.97 (13)O1S—C1S—H1S1109.5
C5—C6—C7119.17 (13)O1S—C1S—H2S1109.5
C5—C6—H6120.4H1S1—C1S—H2S1109.5
C7—C6—H6120.4O1S—C1S—H3S1109.5
C8—C7—C6117.51 (13)H1S1—C1S—H3S1109.5
C8—C7—H7121.2H2S1—C1S—H3S1109.5
C6—C7—H7121.2
C8—N1—C1—O1−179.11 (13)C2—C3—C8—N1−2.46 (15)
C9—N1—C1—O15.0 (2)C1—N1—C8—C7178.43 (14)
C8—N1—C1—C24.55 (15)C9—N1—C8—C7−5.7 (2)
C9—N1—C1—C2−171.35 (12)C1—N1—C8—C3−1.40 (16)
O1—C1—C2—O2−66.31 (17)C9—N1—C8—C3174.45 (13)
N1—C1—C2—O2110.02 (12)C12—N4—C10—C116.11 (14)
O1—C1—C2—C3178.05 (13)C13—N4—C10—C11−165.51 (13)
N1—C1—C2—C3−5.62 (14)C12—N4—C10—C2−112.18 (13)
O1—C1—C2—C1055.09 (18)C13—N4—C10—C276.20 (17)
N1—C1—C2—C10−128.58 (12)O2—C2—C10—N4−60.19 (14)
O2—C2—C3—C468.20 (19)C3—C2—C10—N464.70 (15)
C10—C2—C3—C4−56.9 (2)C1—C2—C10—N4179.38 (11)
C1—C2—C3—C4−177.03 (14)O2—C2—C10—C11−171.72 (10)
O2—C2—C3—C8−110.02 (13)C3—C2—C10—C11−46.83 (16)
C10—C2—C3—C8124.84 (13)C1—C2—C10—C1167.85 (14)
C1—C2—C3—C84.74 (14)C12—N2—C11—O3−176.78 (14)
C8—C3—C4—C50.7 (2)C12—N2—C11—C105.73 (15)
C2—C3—C4—C5−177.33 (13)N4—C10—C11—O3175.06 (13)
C3—C4—C5—F1−179.53 (12)C2—C10—C11—O3−66.68 (17)
C3—C4—C5—C6−0.1 (2)N4—C10—C11—N2−7.34 (14)
F1—C5—C6—C7178.89 (12)C2—C10—C11—N2110.92 (13)
C4—C5—C6—C7−0.6 (2)C13—N4—C12—N3−10.8 (2)
C5—C6—C7—C80.5 (2)C10—N4—C12—N3177.36 (13)
C6—C7—C8—C30.1 (2)C13—N4—C12—N2168.57 (12)
C6—C7—C8—N1−179.68 (13)C10—N4—C12—N2−3.30 (16)
C4—C3—C8—C7−0.8 (2)C11—N2—C12—N3177.68 (13)
C2—C3—C8—C7177.70 (13)C11—N2—C12—N4−1.65 (16)
C4—C3—C8—N1179.06 (12)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O2—H2···N2i0.841.972.8074 (16)171
N3—H3A···O3ii0.882.253.1265 (16)177
N3—H3B···O1iii0.882.122.8490 (17)140
N3—H3B···F1iv0.882.452.8743 (14)110
O1S—H1S4···O30.842.012.846 (3)171
Symmetry codes: (i) −x+1, y−1/2, −z+1/2; (ii) x+1/2, −y+1, z; (iii) −x+1, y+1/2, −z+1/2; (iv) −x+3/2, −y+3/2, −z+1/2.

Experimental details

Crystal data
Chemical formulaC13H13FN4O3·0.5CH4O
Mr308.30
Crystal system, space groupMonoclinic, I2/a
Temperature (K)90
a, b, c (Å)14.3088 (3), 10.7900 (2), 18.1286 (5)
β (°) 107.676 (1)
V (Å3)2666.77 (10)
Z8
Radiation typeCu Kα
µ (mm−1)1.04
Crystal size (mm)0.15 × 0.03 × 0.02
Data collection
DiffractometerBruker X8 Proteum
Absorption correctionMulti-scan
(SADABS in APEX2; Bruker, 2006)
Tmin, Tmax0.805, 0.979
No. of measured, independent and
observed [I > 2σ(I)] reflections		19606, 2448, 2196
Rint0.041
(sin θ/λ)max (Å−1)0.604
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.035, 0.092, 1.04
No. of reflections2448
No. of parameters211
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å−3)0.25, −0.27

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···AD—HH···AD···AD—H···A
O2—H2···N2i0.841.972.8074 (16)170.9
N3—H3A···O3ii0.882.253.1265 (16)177.1
N3—H3B···O1iii0.882.122.8490 (17)139.9
N3—H3B···F1iv0.882.452.8743 (14)110.0
O1S—H1S4···O30.842.012.846 (3)171.2
Symmetry codes: (i) −x+1, y−1/2, −z+1/2; (ii) x+1/2, −y+1, z; (iii) −x+1, y+1/2, −z+1/2; (iv) −x+3/2, −y+3/2, −z+1/2.
 

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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ISSN: 2056-9890
Volume 65| Part 11| November 2009| Pages o2909-o2910
https://doi.org/10.1107/S1600536809043797
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