Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807044212/fl2156sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807044212/fl21564sup2.hkl |
CCDC reference: 663831
Key indicators
- Single-crystal X-ray study
- T = 193 K
- Mean (C-C) = 0.003 Å
- R factor = 0.044
- wR factor = 0.127
- Data-to-parameter ratio = 12.5
checkCIF/PLATON results
No syntax errors found
Alert level C ABSTY03_ALERT_1_C The _exptl_absorpt_correction_type has been given as none. However values have been given for Tmin and Tmax. Remove these if an absorption correction has not been applied. From the CIF: _exptl_absorpt_correction_T_min 0.726 From the CIF: _exptl_absorpt_correction_T_max 0.919 PLAT057_ALERT_3_C Correction for Absorption Required RT(exp) ... 1.13
0 ALERT level A = In general: serious problem 0 ALERT level B = Potentially serious problem 2 ALERT level C = Check and explain 0 ALERT level G = General alerts; check 1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data 0 ALERT type 2 Indicator that the structure model may be wrong or deficient 1 ALERT type 3 Indicator that the structure quality may be low 0 ALERT type 4 Improvement, methodology, query or suggestion 0 ALERT type 5 Informative message, check
Background: Hopkins & Groon (2002); Laufer et al. (2005); Meijer & Raymond (2003). Synthesis: Dalby et al. (1993); Marzilli et al. (1975); Bader & Chiang (1983); Schrauzer (1968). Related purine derivatives: Kowalska et al. (1999); Houlton et al. (1999); Takimoto et al. (1983); Hockova et al. (1999); Sood et al. (1998); Baumann et al. (1994).
The synthetis of 4 (scheme 1) starts from 6- chloropurine 1 showing a tautomerism between the 7H- and the 9H- purine, in which the 9H- isomer is the favoured form. Thus, the direct alkylation of 1 results in mainly N-9- substituted purines with the N-7 substitution as the minor product. In order to obtain a regioselective N-7- alkylation CH3Co(DH)2OH2 was used as an auxiliary. The complex forms an intramolecular N—H ··· O hydrogen bond from purine N-9 to dimethylglyoximato-O-1 and this indirect shielding prevents the N-9- alkylation of 1. As a consequence, the coordination of the cobalt- atom to the N-7 atom of the purine is not possible because of steric hindrance from the neighbouring C-6 substituent. Hence, due to the temporary protection of the N-3 and N-9 positions of 1, by addition of ω- bromoacetophenone, the solid 2 was obtained as the main product and the N-9 alkylated isomer 3 as the minor product. Subsequently, treatment of compound 2 with methanolic ammonia in a high pressure reactor yielded the 6- methoxy- substituted compound 4 (49,5%) and the adenine derivative 5 (34,9%).
Regioselective N-7- alkylation of 6- chloropurine 1 for the preparation of 2-(6-chlor-7H-purin-7-yl)-1-phenylethanone 2: To a solution of methyl(aqua)cobaloxime CH3Co(DH)2OH2 (1.55 mmol) in anhydrous acetonitrile (10 ml) was added 6- chloropurine 1 (1.55 mmol) under vigorous stirring and under light exclusion. After the orange purinecobaloxime- complex had precipitated, K2CO3 (1.55 mmol) and acetonitrile (5 ml) were addded and the reaction mixture was stirred for another 30 min. After the addition of ω- bromoacetophenone (1.55 mmol) the progress of the reaction was monitored by thin - layer chromatography (ethyl acetate: ethanol 9:1). After the reaction was completed, acetonitrile was evaporated and aqueous NaOH (20 ml, 4 M) was added. The aqueous layer was extracted with dichloromethane, and the combined organic extracts were dried over Na2SO4 and evaporated. The residue was purified by flash column chromatography using ethyl acetate: ethanol (9:1) to give 2 (Rf = 0.49 (ethyl acetate: ethanol 9:1)) as a colourless solid (45.0%). The byproduct 2-(6-chlor-9H-purin-9-yl)-1-phenylethanone 3 (Rf = 0.76 (ethyl acetate: ethanol 9:1)) was isolated with a yield of 4.7% (Dalby et al., 1993).
For the synthesis of 2-(6-methoxy-7H-purine-7-yl)-1-phenylethanone 4, NH3 (5 ml) was added to a solution of 3 (1.36 mmol) in 15 ml me thanol. The reaction mixture was heated at T = 363 K in a high pressure reactor from BERGHOF. The progress was again monitored by thin - layer chromatography (ethyl acetate: ethanol 9:1). After cooling to rt, water was added and the mixture extracted with ethyl acetate, dried over Na2SO4 and evaporated. The residue was purified by flash column chromatography using ethyl acetate: ethanol (9:1) to yield 49.5% of 4 (Rf = 0.70, ethyl acetate: ethanol 1:1) and 2-(6-amino-7H-purine-7-yl)-1-phenylethanone 5 (34.9%, Rf = 0.43, ethyl acetate: ethanol 1:1) as a byproduct. Crystals of 4 for X-ray analysis precipitated as colourless sheets by slow evaporation of ethanol- diethylether solution.
Hydrogen atoms attached to carbons were placed at calculated positions with C—H=0.95A% (aromatic) or 0.99–1.00 Å (sp3 C-atom). Hydrogen atom attached to O1W were located in diff. fourier maps. H atoms attached to carbon atoms were refined with isotropic displacement parameters using a riding motion model with fixed C—H distance. The O1W—H distance was free to refine with fixed O1W—H vector direction.
Compound 4 was prepared as an inhibitor of the Vascular Endothelial Growth Factor Receptor (VEGF-R). In 4 the purine system from the cosubstrate ATP of these protein kinases (PK) is combined with an acetophenone moiety in order to interact with the hydrophobic region of the PK. In general, the reversible protein - phosphorylation by PK is an important control mechanism in signal pathways of a cell.
In 4 a water links two symmetry related (2-fold screw axis) purine molecules by H-bonding to N6 and N8, respectively. In turn, each purine molecule hydrogen bonds to two water molecules such that the phenyl rings protrude from opposite sides of an infinite sheet of purine moieties. Thus, a layer-like structure is formed perpendicular to the a axis. The phenyl ring is oriented approximately perpendicular (67.33 (6)°) to the purine ring system.
Background: Hopkins & Groon (2002); Laufer et al. (2005); Meijer & Raymond (2003). Synthesis: Dalby et al. (1993); Marzilli et al. (1975); Bader & Chiang (1983); Schrauzer (1968). Related purine derivatives: Kowalska et al. (1999); Houlton et al. (1999); Takimoto et al. (1983); Hockova et al. (1999); Sood et al. (1998); Baumann et al. (1994).
Data collection: CAD-4 Software (Enraf–Nonius, 1989); cell refinement: CAD-4 Software (Enraf–Nonius, 1989); data reduction: Corinc (Dräger & Gattow 1971); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003) and ORTEP (Johnson, 1968); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997).
C14H12N4O2·H2O | F(000) = 600 |
Mr = 286.29 | Dx = 1.416 Mg m−3 |
Monoclinic, P21/c | Cu Kα radiation, λ = 1.54178 Å |
Hall symbol: -P 2ybc | Cell parameters from 25 reflections |
a = 12.2729 (6) Å | θ = 61–70° |
b = 8.2830 (7) Å | µ = 0.86 mm−1 |
c = 14.3335 (10) Å | T = 193 K |
β = 112.851 (3)° | Plate, colourless |
V = 1342.74 (16) Å3 | 0.40 × 0.20 × 0.10 mm |
Z = 4 |
Enraf–Nonius CAD-4 diffractometer | Rint = 0.083 |
Radiation source: rotating anode | θmax = 70.2°, θmin = 3.9° |
Graphite monochromator | h = −13→14 |
ω/2θ scans | k = 0→10 |
2645 measured reflections | l = −17→0 |
2534 independent reflections | 3 standard reflections every 60 min |
2089 reflections with I > 2σ(I) | intensity decay: 5% |
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)] = 0.044 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.127 | Only H-atom displacement parameters refined |
S = 1.08 | w = 1/[σ2(Fo2) + (0.0712P)2 + 0.325P] where P = (Fo2 + 2Fc2)/3 |
2534 reflections | (Δ/σ)max < 0.001 |
202 parameters | Δρmax = 0.23 e Å−3 |
0 restraints | Δρmin = −0.27 e Å−3 |
C14H12N4O2·H2O | V = 1342.74 (16) Å3 |
Mr = 286.29 | Z = 4 |
Monoclinic, P21/c | Cu Kα radiation |
a = 12.2729 (6) Å | µ = 0.86 mm−1 |
b = 8.2830 (7) Å | T = 193 K |
c = 14.3335 (10) Å | 0.40 × 0.20 × 0.10 mm |
β = 112.851 (3)° |
Enraf–Nonius CAD-4 diffractometer | Rint = 0.083 |
2645 measured reflections | 3 standard reflections every 60 min |
2534 independent reflections | intensity decay: 5% |
2089 reflections with I > 2σ(I) |
R[F2 > 2σ(F2)] = 0.044 | 0 restraints |
wR(F2) = 0.127 | Only H-atom displacement parameters refined |
S = 1.08 | Δρmax = 0.23 e Å−3 |
2534 reflections | Δρmin = −0.27 e Å−3 |
202 parameters |
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 > σ(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 | ||
N1 | 0.18404 (12) | 0.47672 (17) | 0.62611 (10) | 0.0285 (3) | |
C2 | 0.16775 (14) | 0.32546 (19) | 0.58263 (12) | 0.0257 (4) | |
C3 | 0.18454 (14) | 0.1669 (2) | 0.61821 (12) | 0.0262 (4) | |
N4 | 0.15423 (12) | 0.04636 (17) | 0.55245 (11) | 0.0307 (3) | |
C5 | 0.10739 (15) | 0.0839 (2) | 0.45274 (13) | 0.0330 (4) | |
H5 | 0.0840 | −0.0050 | 0.4073 | 0.037 (5)* | |
N6 | 0.09001 (13) | 0.22894 (19) | 0.41046 (10) | 0.0329 (4) | |
C7 | 0.12163 (14) | 0.3509 (2) | 0.47865 (12) | 0.0282 (4) | |
N8 | 0.11165 (13) | 0.51367 (19) | 0.45755 (11) | 0.0339 (4) | |
C9 | 0.14978 (15) | 0.5824 (2) | 0.54765 (13) | 0.0331 (4) | |
H9 | 0.1509 | 0.6954 | 0.5624 | 0.031 (5)* | |
O10 | 0.23226 (11) | 0.14118 (14) | 0.71795 (9) | 0.0325 (3) | |
C11 | 0.2425 (2) | −0.0240 (2) | 0.75123 (15) | 0.0488 (6) | |
H11A | 0.1661 | −0.0783 | 0.7185 | 0.068 (5)* | |
H11B | 0.2664 | −0.0271 | 0.8249 | 0.068 (5)* | |
H11C | 0.3021 | −0.0792 | 0.7329 | 0.068 (5)* | |
C12 | 0.23133 (15) | 0.5177 (2) | 0.73339 (12) | 0.0294 (4) | |
H12A | 0.2233 | 0.4235 | 0.7728 | 0.044 (4)* | |
H12B | 0.1849 | 0.6077 | 0.7448 | 0.044 (4)* | |
C13 | 0.36068 (15) | 0.5666 (2) | 0.77075 (12) | 0.0294 (4) | |
O14 | 0.41546 (12) | 0.5476 (2) | 0.71708 (10) | 0.0485 (4) | |
C15 | 0.41426 (14) | 0.6416 (2) | 0.87259 (12) | 0.0278 (4) | |
C16 | 0.52074 (16) | 0.7238 (3) | 0.89910 (15) | 0.0397 (5) | |
H16 | 0.5591 | 0.7292 | 0.8530 | 0.049 (6)* | |
C17 | 0.57072 (18) | 0.7978 (3) | 0.99248 (17) | 0.0478 (5) | |
H17 | 0.6427 | 0.8558 | 1.0099 | 0.077 (9)* | |
C18 | 0.51658 (17) | 0.7878 (3) | 1.06072 (15) | 0.0435 (5) | |
H18 | 0.5517 | 0.8378 | 1.1252 | 0.051 (6)* | |
C19 | 0.41193 (17) | 0.7056 (3) | 1.03499 (14) | 0.0425 (5) | |
H19 | 0.3749 | 0.6983 | 1.0820 | 0.069 (8)* | |
C20 | 0.36001 (16) | 0.6333 (2) | 0.94135 (14) | 0.0367 (4) | |
H20 | 0.2870 | 0.5778 | 0.9238 | 0.048 (6)* | |
O1W | 0.04215 (13) | 0.77041 (17) | 0.30574 (9) | 0.0418 (4) | |
H1W | 0.0523 (2) | 0.670 (2) | 0.3418 (7) | 0.068 (6)* | |
H2W | −0.0121 (12) | 0.7424 (6) | 0.2431 (13) | 0.068 (6)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.0327 (7) | 0.0265 (7) | 0.0236 (7) | 0.0001 (6) | 0.0079 (6) | −0.0012 (5) |
C2 | 0.0244 (8) | 0.0289 (8) | 0.0228 (8) | 0.0008 (6) | 0.0081 (6) | −0.0006 (6) |
C3 | 0.0233 (7) | 0.0295 (9) | 0.0242 (8) | 0.0001 (6) | 0.0075 (6) | −0.0013 (6) |
N4 | 0.0296 (7) | 0.0298 (7) | 0.0300 (8) | 0.0000 (6) | 0.0087 (6) | −0.0044 (6) |
C5 | 0.0313 (9) | 0.0377 (10) | 0.0286 (9) | −0.0013 (7) | 0.0100 (7) | −0.0091 (8) |
N6 | 0.0332 (8) | 0.0404 (9) | 0.0229 (7) | −0.0004 (6) | 0.0085 (6) | −0.0041 (6) |
C7 | 0.0259 (8) | 0.0350 (9) | 0.0219 (8) | 0.0001 (7) | 0.0074 (6) | 0.0002 (7) |
N8 | 0.0368 (8) | 0.0342 (8) | 0.0270 (7) | −0.0006 (6) | 0.0081 (6) | 0.0040 (6) |
C9 | 0.0364 (9) | 0.0286 (9) | 0.0314 (9) | 0.0020 (7) | 0.0101 (7) | 0.0041 (7) |
O10 | 0.0399 (7) | 0.0281 (6) | 0.0231 (6) | −0.0008 (5) | 0.0055 (5) | 0.0030 (5) |
C11 | 0.0731 (15) | 0.0312 (10) | 0.0331 (10) | −0.0064 (10) | 0.0109 (10) | 0.0067 (8) |
C12 | 0.0342 (9) | 0.0300 (9) | 0.0239 (8) | −0.0013 (7) | 0.0112 (7) | −0.0038 (7) |
C13 | 0.0325 (9) | 0.0295 (8) | 0.0264 (8) | 0.0029 (7) | 0.0116 (7) | 0.0036 (7) |
O14 | 0.0405 (7) | 0.0767 (11) | 0.0337 (7) | −0.0043 (7) | 0.0203 (6) | −0.0095 (7) |
C15 | 0.0285 (8) | 0.0275 (8) | 0.0259 (8) | 0.0038 (6) | 0.0088 (7) | 0.0028 (7) |
C16 | 0.0321 (9) | 0.0485 (12) | 0.0407 (10) | −0.0040 (8) | 0.0164 (8) | −0.0058 (9) |
C17 | 0.0323 (10) | 0.0568 (13) | 0.0518 (12) | −0.0133 (9) | 0.0136 (9) | −0.0167 (11) |
C18 | 0.0375 (10) | 0.0517 (12) | 0.0356 (10) | −0.0015 (9) | 0.0080 (8) | −0.0142 (9) |
C19 | 0.0398 (10) | 0.0588 (13) | 0.0307 (10) | −0.0053 (9) | 0.0158 (8) | −0.0084 (9) |
C20 | 0.0338 (9) | 0.0459 (11) | 0.0312 (9) | −0.0086 (8) | 0.0136 (7) | −0.0047 (8) |
O1W | 0.0568 (9) | 0.0334 (7) | 0.0272 (6) | −0.0036 (6) | 0.0075 (6) | −0.0010 (5) |
N1—C9 | 1.357 (2) | C12—C13 | 1.520 (2) |
N1—C2 | 1.379 (2) | C12—H12A | 0.9900 |
N1—C12 | 1.457 (2) | C12—H12B | 0.9900 |
C2—C7 | 1.389 (2) | C13—O14 | 1.213 (2) |
C2—C3 | 1.395 (2) | C13—C15 | 1.484 (2) |
C3—N4 | 1.323 (2) | C15—C20 | 1.389 (2) |
C3—O10 | 1.335 (2) | C15—C16 | 1.389 (3) |
N4—C5 | 1.353 (2) | C16—C17 | 1.380 (3) |
C5—N6 | 1.325 (2) | C16—H16 | 0.9500 |
C5—H5 | 0.9500 | C17—C18 | 1.382 (3) |
N6—C7 | 1.353 (2) | C17—H17 | 0.9500 |
C7—N8 | 1.377 (2) | C18—C19 | 1.372 (3) |
N8—C9 | 1.320 (2) | C18—H18 | 0.9500 |
C9—H9 | 0.9588 | C19—C20 | 1.379 (3) |
O10—C11 | 1.438 (2) | C19—H19 | 0.9500 |
C11—H11A | 0.9800 | C20—H20 | 0.9500 |
C11—H11B | 0.9800 | O1W—H1W | 0.9625 |
C11—H11C | 0.9800 | O1W—H2W | 0.9160 |
C9—N1—C2 | 105.53 (14) | N1—C12—C13 | 111.55 (13) |
C9—N1—C12 | 126.35 (15) | N1—C12—H12A | 109.3 |
C2—N1—C12 | 128.10 (14) | C13—C12—H12A | 109.3 |
N1—C2—C7 | 105.92 (14) | N1—C12—H12B | 109.3 |
N1—C2—C3 | 135.67 (15) | C13—C12—H12B | 109.3 |
C7—C2—C3 | 118.40 (15) | H12A—C12—H12B | 108.0 |
N4—C3—O10 | 121.82 (15) | O14—C13—C15 | 122.37 (16) |
N4—C3—C2 | 119.29 (15) | O14—C13—C12 | 120.15 (15) |
O10—C3—C2 | 118.88 (15) | C15—C13—C12 | 117.46 (14) |
C3—N4—C5 | 117.73 (15) | C20—C15—C16 | 119.30 (16) |
N6—C5—N4 | 128.18 (16) | C20—C15—C13 | 121.72 (16) |
N6—C5—H5 | 115.9 | C16—C15—C13 | 118.97 (16) |
N4—C5—H5 | 115.9 | C17—C16—C15 | 119.96 (18) |
C5—N6—C7 | 113.35 (14) | C17—C16—H16 | 120.0 |
N6—C7—N8 | 126.59 (15) | C15—C16—H16 | 120.0 |
N6—C7—C2 | 123.01 (16) | C16—C17—C18 | 120.34 (18) |
N8—C7—C2 | 110.39 (15) | C16—C17—H17 | 119.8 |
C9—N8—C7 | 103.88 (14) | C18—C17—H17 | 119.8 |
N8—C9—N1 | 114.27 (16) | C19—C18—C17 | 119.77 (18) |
N8—C9—H9 | 127.3 | C19—C18—H18 | 120.1 |
N1—C9—H9 | 118.3 | C17—C18—H18 | 120.1 |
C3—O10—C11 | 116.91 (14) | C18—C19—C20 | 120.52 (18) |
O10—C11—H11A | 109.5 | C18—C19—H19 | 119.7 |
O10—C11—H11B | 109.5 | C20—C19—H19 | 119.7 |
H11A—C11—H11B | 109.5 | C19—C20—C15 | 120.10 (17) |
O10—C11—H11C | 109.5 | C19—C20—H20 | 120.0 |
H11A—C11—H11C | 109.5 | C15—C20—H20 | 120.0 |
H11B—C11—H11C | 109.5 | H1W—O1W—H2W | 101.6 |
C9—N1—C2—C7 | −1.15 (18) | C2—N1—C9—N8 | 0.7 (2) |
C12—N1—C2—C7 | −179.42 (15) | C12—N1—C9—N8 | 179.03 (15) |
C9—N1—C2—C3 | −179.88 (19) | N4—C3—O10—C11 | −3.8 (2) |
C12—N1—C2—C3 | 1.9 (3) | C2—C3—O10—C11 | 177.03 (16) |
N1—C2—C3—N4 | 177.35 (17) | C9—N1—C12—C13 | −78.3 (2) |
C7—C2—C3—N4 | −1.3 (2) | C2—N1—C12—C13 | 99.68 (19) |
N1—C2—C3—O10 | −3.5 (3) | N1—C12—C13—O14 | −9.8 (2) |
C7—C2—C3—O10 | 177.92 (14) | N1—C12—C13—C15 | 168.46 (14) |
O10—C3—N4—C5 | −179.43 (15) | O14—C13—C15—C20 | −166.61 (18) |
C2—C3—N4—C5 | −0.3 (2) | C12—C13—C15—C20 | 15.2 (2) |
C3—N4—C5—N6 | 2.0 (3) | O14—C13—C15—C16 | 14.2 (3) |
N4—C5—N6—C7 | −1.8 (3) | C12—C13—C15—C16 | −164.03 (16) |
C5—N6—C7—N8 | −178.59 (16) | C20—C15—C16—C17 | −0.8 (3) |
C5—N6—C7—C2 | 0.0 (2) | C13—C15—C16—C17 | 178.45 (19) |
N1—C2—C7—N6 | −177.56 (15) | C15—C16—C17—C18 | 1.3 (3) |
C3—C2—C7—N6 | 1.4 (2) | C16—C17—C18—C19 | −0.7 (3) |
N1—C2—C7—N8 | 1.25 (19) | C17—C18—C19—C20 | −0.3 (3) |
C3—C2—C7—N8 | −179.76 (14) | C18—C19—C20—C15 | 0.8 (3) |
N6—C7—N8—C9 | 177.95 (17) | C16—C15—C20—C19 | −0.3 (3) |
C2—C7—N8—C9 | −0.81 (19) | C13—C15—C20—C19 | −179.46 (18) |
C7—N8—C9—N1 | 0.1 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
O1W—H1W···N8 | 0.96 | 2.00 | 2.923 (2) | 159 |
O1W—H2W···N6i | 0.92 | 2.03 | 2.9066 (19) | 159 |
Symmetry code: (i) −x, y+1/2, −z+1/2. |
Experimental details
Crystal data | |
Chemical formula | C14H12N4O2·H2O |
Mr | 286.29 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 193 |
a, b, c (Å) | 12.2729 (6), 8.2830 (7), 14.3335 (10) |
β (°) | 112.851 (3) |
V (Å3) | 1342.74 (16) |
Z | 4 |
Radiation type | Cu Kα |
µ (mm−1) | 0.86 |
Crystal size (mm) | 0.40 × 0.20 × 0.10 |
Data collection | |
Diffractometer | Enraf–Nonius CAD-4 |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 2645, 2534, 2089 |
Rint | 0.083 |
(sin θ/λ)max (Å−1) | 0.610 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.044, 0.127, 1.08 |
No. of reflections | 2534 |
No. of parameters | 202 |
H-atom treatment | Only H-atom displacement parameters refined |
Δρmax, Δρmin (e Å−3) | 0.23, −0.27 |
Computer programs: CAD-4 Software (Enraf–Nonius, 1989), Corinc (Dräger & Gattow 1971), SIR92 (Altomare et al., 1994), SHELXL97 (Sheldrick, 1997), PLATON (Spek, 2003) and ORTEP (Johnson, 1968).
D—H···A | D—H | H···A | D···A | D—H···A |
O1W—H1W···N8 | 0.96 | 2.00 | 2.923 (2) | 158.9 |
O1W—H2W···N6i | 0.92 | 2.03 | 2.9066 (19) | 158.7 |
Symmetry code: (i) −x, y+1/2, −z+1/2. |
Subscribe to Acta Crystallographica Section E: Crystallographic Communications
The full text of this article is available to subscribers to the journal.
- Information on subscribing
- Sample issue
- If you have already subscribed, you may need to register
Compound 4 was prepared as an inhibitor of the Vascular Endothelial Growth Factor Receptor (VEGF-R). In 4 the purine system from the cosubstrate ATP of these protein kinases (PK) is combined with an acetophenone moiety in order to interact with the hydrophobic region of the PK. In general, the reversible protein - phosphorylation by PK is an important control mechanism in signal pathways of a cell.
In 4 a water links two symmetry related (2-fold screw axis) purine molecules by H-bonding to N6 and N8, respectively. In turn, each purine molecule hydrogen bonds to two water molecules such that the phenyl rings protrude from opposite sides of an infinite sheet of purine moieties. Thus, a layer-like structure is formed perpendicular to the a axis. The phenyl ring is oriented approximately perpendicular (67.33 (6)°) to the purine ring system.