3-(2-Amino-1-methyl-4-oxo-4,5-dihydro-1H-imidazol-5-yl)-5-fluoro-3-hydr-oxy-1-methyl-indolin-2-one methanol hemisolvate.

In the title compound, C(13)H(13)FN(4)O(3)·0.5CH(3)OH, mol-ecules are packed in the crystal structure by a series of O-H⋯N, N-H⋯O, N-H⋯F and O-H⋯O inter-molecular 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 ▶); 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

Crystal data

C13H13FN4O3·0.5CH4O

M = 308.30

Monoclinic,

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 ▶) T min = 0.805, T max = 0.979

19606 measured reflections

2448 independent reflections

2196 reflections with I > 2σ(I)

R int = 0.041

Refinement

R[F 2 > 2σ(F 2)] = 0.035

wR(F 2) = 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

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.

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

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809043797/hg2556Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C13H13FN4O3·0.5CH4O	F(000) = 1288
Mr = 308.30	Dx = 1.536 Mg m−3
Monoclinic, I2/a	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: -I 2ya	Cell parameters from 9961 reflections
a = 14.3088 (3) Å	θ = 4.8–68.5°
b = 10.7900 (2) Å	µ = 1.04 mm−1
c = 18.1286 (5) Å	T = 90 K
β = 107.676 (1)°	Rod, colourless
V = 2666.77 (10) Å3	0.15 × 0.03 × 0.02 mm
Z = 8

Bruker X8 Proteum diffractometer	2448 independent reflections
Radiation source: fine-focus rotating anode	2196 reflections with I > 2σ(I)
graded multilayer optics	Rint = 0.041
Detector resolution: 5.6 pixels mm-1	θmax = 68.5°, θmin = 4.8°
φ and ω scans	h = −17→17
Absorption correction: multi-scan (SADABS in APEX2; Bruker, 2006)	k = −13→13
Tmin = 0.805, Tmax = 0.979	l = −17→21
19606 measured reflections

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)] = 0.035	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.092	H-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 parameters	Δρmax = 0.25 e Å−3
0 restraints	Δρmin = −0.27 e Å−3

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.

	x	y	z	Uiso*/Ueq	Occ. (<1)
F1	0.71683 (6)	0.82226 (8)	0.40909 (5)	0.0226 (2)
O1	0.34944 (7)	0.34900 (10)	0.34227 (6)	0.0220 (2)
N1	0.40050 (8)	0.53388 (11)	0.40330 (7)	0.0180 (3)
C1	0.40738 (10)	0.43524 (13)	0.35922 (8)	0.0171 (3)
O2	0.56972 (7)	0.35213 (9)	0.37870 (6)	0.0182 (2)
H2	0.5465	0.2822	0.3628	0.027*
N2	0.48670 (8)	0.61111 (11)	0.17484 (7)	0.0186 (3)
C2	0.50466 (10)	0.44565 (13)	0.33829 (8)	0.0164 (3)
O3	0.34268 (7)	0.56370 (9)	0.20215 (6)	0.0207 (2)
N3	0.64656 (9)	0.58544 (12)	0.16571 (8)	0.0230 (3)
H3A	0.7006	0.5411	0.1762	0.028*
H3B	0.6417	0.6549	0.1393	0.028*
C3	0.54173 (10)	0.57182 (13)	0.37146 (8)	0.0162 (3)
N4	0.57662 (8)	0.44285 (11)	0.22994 (7)	0.0168 (3)
C4	0.62309 (10)	0.64045 (13)	0.37024 (8)	0.0168 (3)
H4	0.6668	0.6122	0.3436	0.020*
C5	0.63765 (10)	0.75245 (14)	0.40985 (8)	0.0181 (3)
C6	0.57663 (11)	0.79772 (14)	0.44928 (8)	0.0205 (3)
H6	0.5904	0.8747	0.4758	0.025*
C7	0.49419 (11)	0.72920 (14)	0.44984 (8)	0.0206 (3)
H7	0.4503	0.7582	0.4762	0.025*
C8	0.47874 (10)	0.61742 (13)	0.41062 (8)	0.0174 (3)
C9	0.32581 (11)	0.54673 (15)	0.44237 (9)	0.0227 (3)
H9A	0.2715	0.5971	0.4105	0.034*
H9B	0.3544	0.5872	0.4926	0.034*
H9C	0.3013	0.4646	0.4503	0.034*
C10	0.48606 (10)	0.43188 (13)	0.25013 (8)	0.0158 (3)
H10	0.4521	0.3519	0.2308	0.019*
C11	0.42843 (10)	0.54179 (13)	0.20572 (8)	0.0166 (3)
C12	0.57275 (10)	0.54783 (13)	0.18962 (8)	0.0174 (3)
C13	0.65283 (10)	0.34938 (13)	0.24071 (9)	0.0200 (3)
H13A	0.6606	0.3276	0.1904	0.030*
H13B	0.6344	0.2753	0.2644	0.030*
H13C	0.7149	0.3822	0.2746	0.030*
O1S	0.2149 (2)	0.6430 (4)	0.05671 (19)	0.0769 (13)	0.50
H1S4	0.2574	0.6239	0.0984	0.115*	0.50
C1S	0.2489 (9)	0.6226 (3)	−0.0003 (6)	0.0403 (9)	0.5
H1S1	0.3121	0.6649	0.0091	0.060*	0.50
H2S1	0.2026	0.6540	−0.0482	0.060*	0.50
H3S1	0.2580	0.5332	−0.0051	0.060*	0.50

	U11	U22	U33	U12	U13	U23
F1	0.0206 (4)	0.0228 (5)	0.0262 (5)	−0.0075 (3)	0.0100 (3)	−0.0027 (3)
O1	0.0189 (5)	0.0224 (5)	0.0266 (6)	−0.0049 (4)	0.0098 (4)	−0.0021 (4)
N1	0.0153 (6)	0.0215 (6)	0.0188 (6)	−0.0016 (5)	0.0076 (5)	−0.0022 (5)
C1	0.0156 (7)	0.0204 (7)	0.0158 (7)	0.0003 (5)	0.0056 (5)	0.0016 (5)
O2	0.0172 (5)	0.0165 (5)	0.0200 (5)	0.0007 (4)	0.0043 (4)	0.0002 (4)
N2	0.0174 (6)	0.0192 (6)	0.0203 (6)	0.0003 (5)	0.0073 (5)	0.0020 (5)
C2	0.0138 (6)	0.0176 (7)	0.0180 (7)	−0.0001 (5)	0.0052 (5)	0.0006 (5)
O3	0.0153 (5)	0.0223 (5)	0.0246 (5)	0.0007 (4)	0.0065 (4)	0.0000 (4)
N3	0.0202 (6)	0.0225 (6)	0.0297 (7)	0.0015 (5)	0.0129 (5)	0.0070 (5)
C3	0.0160 (7)	0.0175 (7)	0.0145 (6)	0.0016 (5)	0.0039 (5)	0.0012 (5)
N4	0.0158 (6)	0.0166 (6)	0.0206 (6)	0.0013 (4)	0.0096 (5)	0.0014 (5)
C4	0.0152 (6)	0.0196 (7)	0.0158 (7)	0.0008 (5)	0.0050 (5)	0.0004 (5)
C5	0.0158 (6)	0.0197 (7)	0.0180 (7)	−0.0029 (5)	0.0037 (5)	0.0029 (5)
C6	0.0231 (7)	0.0192 (7)	0.0184 (7)	−0.0004 (6)	0.0051 (6)	−0.0032 (6)
C7	0.0199 (7)	0.0241 (7)	0.0190 (7)	0.0013 (6)	0.0078 (6)	−0.0028 (6)
C8	0.0147 (6)	0.0211 (7)	0.0160 (7)	0.0000 (5)	0.0039 (5)	0.0012 (5)
C9	0.0184 (7)	0.0321 (8)	0.0206 (7)	−0.0025 (6)	0.0103 (6)	−0.0039 (6)
C10	0.0133 (7)	0.0168 (7)	0.0185 (7)	−0.0015 (5)	0.0069 (5)	−0.0010 (5)
C11	0.0160 (7)	0.0176 (7)	0.0160 (7)	−0.0003 (5)	0.0044 (5)	−0.0027 (5)
C12	0.0181 (7)	0.0184 (7)	0.0160 (7)	−0.0015 (5)	0.0058 (5)	−0.0016 (5)
C13	0.0183 (7)	0.0197 (7)	0.0245 (7)	0.0034 (6)	0.0102 (6)	0.0008 (6)
O1S	0.0548 (19)	0.136 (4)	0.0458 (18)	0.060 (2)	0.0247 (16)	0.038 (2)
C1S	0.0351 (15)	0.0419 (18)	0.0384 (17)	0.012 (4)	0.0029 (13)	−0.033 (4)

F1—C5	1.3641 (16)	C4—C5	1.389 (2)
O1—C1	1.2220 (17)	C4—H4	0.9500
N1—C1	1.3525 (19)	C5—C6	1.375 (2)
N1—C8	1.4117 (18)	C6—C7	1.395 (2)
N1—C9	1.4570 (18)	C6—H6	0.9500
C1—C2	1.5539 (19)	C7—C8	1.383 (2)
O2—C2	1.4168 (16)	C7—H7	0.9500
O2—H2	0.8400	C9—H9A	0.9800
N2—C11	1.3606 (18)	C9—H9B	0.9800
N2—C12	1.3615 (18)	C9—H9C	0.9800
C2—C3	1.5175 (19)	C10—C11	1.5270 (19)
C2—C10	1.546 (2)	C10—H10	1.0000
O3—C11	1.2318 (17)	C13—H13A	0.9800
N3—C12	1.3214 (19)	C13—H13B	0.9800
N3—H3A	0.8800	C13—H13C	0.9800
N3—H3B	0.8800	O1S—C1S	1.288 (10)
C3—C4	1.386 (2)	O1S—H1S4	0.8400
C3—C8	1.395 (2)	C1S—H1S1	0.9800
N4—C12	1.3401 (19)	C1S—H2S1	0.9800
N4—C13	1.4543 (18)	C1S—H3S1	0.9800
N4—C10	1.4544 (17)
C1—N1—C8	111.10 (12)	C7—C8—C3	122.81 (13)
C1—N1—C9	123.91 (12)	C7—C8—N1	127.11 (13)
C8—N1—C9	124.85 (12)	C3—C8—N1	110.08 (12)
O1—C1—N1	125.61 (13)	N1—C9—H9A	109.5
O1—C1—C2	125.69 (13)	N1—C9—H9B	109.5
N1—C1—C2	108.59 (11)	H9A—C9—H9B	109.5
C2—O2—H2	109.5	N1—C9—H9C	109.5
C11—N2—C12	105.90 (12)	H9A—C9—H9C	109.5
O2—C2—C3	109.77 (11)	H9B—C9—H9C	109.5
O2—C2—C10	110.25 (11)	N4—C10—C11	100.60 (11)
C3—C2—C10	115.20 (11)	N4—C10—C2	111.45 (11)
O2—C2—C1	108.60 (11)	C11—C10—C2	111.49 (11)
C3—C2—C1	101.49 (11)	N4—C10—H10	111.0
C10—C2—C1	111.09 (11)	C11—C10—H10	111.0
C12—N3—H3A	120.0	C2—C10—H10	111.0
C12—N3—H3B	120.0	O3—C11—N2	126.72 (13)
H3A—N3—H3B	120.0	O3—C11—C10	123.14 (13)
C4—C3—C8	119.69 (13)	N2—C11—C10	110.09 (11)
C4—C3—C2	131.87 (13)	N3—C12—N4	122.26 (13)
C8—C3—C2	108.42 (12)	N3—C12—N2	123.14 (13)
C12—N4—C13	124.37 (12)	N4—C12—N2	114.60 (12)
C12—N4—C10	108.28 (11)	N4—C13—H13A	109.5
C13—N4—C10	126.78 (11)	N4—C13—H13B	109.5
C3—C4—C5	116.85 (13)	H13A—C13—H13B	109.5
C3—C4—H4	121.6	N4—C13—H13C	109.5
C5—C4—H4	121.6	H13A—C13—H13C	109.5
F1—C5—C6	118.00 (13)	H13B—C13—H13C	109.5
F1—C5—C4	118.03 (12)	C1S—O1S—H1S4	109.5
C6—C5—C4	123.97 (13)	O1S—C1S—H1S1	109.5
C5—C6—C7	119.17 (13)	O1S—C1S—H2S1	109.5
C5—C6—H6	120.4	H1S1—C1S—H2S1	109.5
C7—C6—H6	120.4	O1S—C1S—H3S1	109.5
C8—C7—C6	117.51 (13)	H1S1—C1S—H3S1	109.5
C8—C7—H7	121.2	H2S1—C1S—H3S1	109.5
C6—C7—H7	121.2
C8—N1—C1—O1	−179.11 (13)	C2—C3—C8—N1	−2.46 (15)
C9—N1—C1—O1	5.0 (2)	C1—N1—C8—C7	178.43 (14)
C8—N1—C1—C2	4.55 (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—C3	174.45 (13)
N1—C1—C2—O2	110.02 (12)	C12—N4—C10—C11	6.11 (14)
O1—C1—C2—C3	178.05 (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—C10	55.09 (18)	C13—N4—C10—C2	76.20 (17)
N1—C1—C2—C10	−128.58 (12)	O2—C2—C10—N4	−60.19 (14)
O2—C2—C3—C4	68.20 (19)	C3—C2—C10—N4	64.70 (15)
C10—C2—C3—C4	−56.9 (2)	C1—C2—C10—N4	179.38 (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—C8	124.84 (13)	C1—C2—C10—C11	67.85 (14)
C1—C2—C3—C8	4.74 (14)	C12—N2—C11—O3	−176.78 (14)
C8—C3—C4—C5	0.7 (2)	C12—N2—C11—C10	5.73 (15)
C2—C3—C4—C5	−177.33 (13)	N4—C10—C11—O3	175.06 (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—C7	178.89 (12)	C2—C10—C11—N2	110.92 (13)
C4—C5—C6—C7	−0.6 (2)	C13—N4—C12—N3	−10.8 (2)
C5—C6—C7—C8	0.5 (2)	C10—N4—C12—N3	177.36 (13)
C6—C7—C8—C3	0.1 (2)	C13—N4—C12—N2	168.57 (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—N3	177.68 (13)
C2—C3—C8—C7	177.70 (13)	C11—N2—C12—N4	−1.65 (16)
C4—C3—C8—N1	179.06 (12)

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

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) ; (ii) ; (iii) ; (iv) .