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Erlotinib [systematic name: N-(3-ethynylphen­yl)-6,7-bis­(2-methoxy­ethoxy)quinazolin-4-amine], a small-mol­ecule epi­der­mal growth factor receptor inhibitor, useful for the treatment of non-small-cell lung cancer, has been crystallized as erlotinib monohydrate, C22H23N3O4·H2O, (I), the erlotinib hemioxalate salt [systematic name: 4-amino-N-(3-ethynyl­phen­yl)-6,7-bis­(2-methoxy­ethoxy)quinazolin-1-ium hemioxalate], C22H24N3O4+·0.5C2O42-, (II), and the cocrystal erlotinib fumaric acid hemisolvate dihydrate, C22H23N3O4·0.5C4H4O4·2H2O, (III). In (II) and (III), the oxalate anion and the fumaric acid mol­ecule are located across inversion centres. The water mol­ecules in (I) and (III) play an active role in hydrogen-bonding inter­actions which lead to the formation of tetra­meric and hexa­meric hydrogen-bonded networks, while in (II) the cations and anions form a tetra­meric hydrogen-bonded network in the crystal packing. The title multicomponent crystals of erlotinib have been elucidated to study the assembly of mol­ecules through inter­molecular inter­actions, such as hydrogen bonds and aromatic [pi]-[pi] stacking.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270109052470/sf3120sup1.cif
Contains datablocks I, II, III, global

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270109052470/sf3120Isup2.hkl
Contains datablock I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270109052470/sf3120IIsup3.hkl
Contains datablock II

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270109052470/sf3120IIIsup4.hkl
Contains datablock III

CCDC references: 765476; 765477; 765478

Comment top

Understanding the various types and strengths of noncovalent interactions that bind molecules in crystal structures is very important for molecular recognition in chemical and complex biological processes (Glusker, 1998). These studies are significant because of their application in crystal engineering, supramolecular chemistry, and the design of functional materials and drugs (Desiraju & Steiner, 1999). In this context, the multicomponent crystals of the drug molecule of erlotinib were grown. Erlotinib is a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (Rusch et al., 1996). EGFR is a protein tyrosine kinase that plays a crucial role in signal transduction pathways which regulate key cellular functions such as survival and proliferation. Over- expression of EGFR tyrosine kinase is reported in a variety of human tumours and is associated with poor prognosis (Yarden & Ullrich, 1988). Similar to gefitinib, erlotinib specifically targets the EGFR tyrosine kinase, which is highly expressed and occasionally mutated in various forms of cancer. Gefitinib (Iressa) and erlotinib (Tarceca) are the two clinically used EGFR tyrosine kinase inhibitors (TKIs) that demonstrate significant efficacy in non-small-cell lung cancer, leading to FDA (US Food and Drug Administration) approval for the treatment of this refractory disease. Multicomponent crystals are composed of two or more components associated through intermolecular interactions, and the salts and cocrystals can both be described as multicomponent crystals (Stahly, 2007). Recently, we have reported the crystal structure of erlotinib hydrochloride (Selvanayagam et al., 2008). In the present study, the crystal structures of erlotinib hydrate, (I), erlotinib hemioxalate, (II), and erlotinib hemifumaric acid dihydrate, (III), and their intermolecular interactions which hold the assembly of molecules in the crystalline lattice are presented.

The asymmetric unit of (I) contains one erlotinib molecule and one water molecule, the asymmetric unit of (II) contains one erlotinib cation protonated at atom N1 and an oxalate dianion lying across an inversion centre, while the asymmetric unit of (III) consists of one erlotinib molecule and fumaric acid lying across an inversion centre and two water molecules (Figs. 1, 2, 3). The bond distances and angles of the erlotinib molecules in (I), (II) and (III) are similar and agree well with the values found in related structures (Selvanayagam et al., 2008; Xia, 2005; Ghosh et al., 2001). In (I), the atoms C13/O2/C14 of the 2-methoxyethoxy side chain are disordered over two sites, with occupancies of 0.554 (7) and 0.446 (7), and in (III) the atoms O5/O6/C23/C24 of the hemifumaric acid are disordered over two sites, with occupancies of 0.55 (2) and 0.45 (2).

The inequality of the C—O distances and O—C—C angles (Table 1) confirms the carboxylate group (O5/O6/C23) in (II), while in (III) the near equality of C—O distances and O—C—C angles (Table 1) clearly shows the existence of the carboxylic group (O5/O6/C23). In (III), the O—H bond of the carboxyl group is in cis conformation with respect to the CO bond, as evidenced from the H5O—O5—C23—O6 torsion angle of 12.7°.

The crystal structure of the erlotinib inhibitor in complex with the EGFR kinase domain [Stamos et al., 2002; Protein Data Bank (PDB; Berman et al., 2000) entry 1m17)] is available and the extracted ligand structure is used for comparison. The torsion angles C3—C2—N3—C15 and C2—N3—C15—C16 define the relative orientation of the quinazoline and ethynylphenyl moieties. In all three structures the two ring systems are relatively close to coplanar; the dihedral angles between these two ring moieties being 6.2 (1) for (I), 2.8 (1) for (II) and 22.8 (1)° for (III). The corresponding interplanar angle between the aromatic ring systems is 42° for the erlotinib–EGFR kinase complex and 34.4 (1)° for erlotinib HCl. However, in (III) and in both the erlotinib–EGFR kinase complex and erlotinib HCl there is a rotation of the ethynylphenyl ring with respect to the quinazoline ring system.

An overlay of the erlotinib molecules, superimposing the quinazoline ring system, reveals the twist in the ethynylphenyl ring with respect to the quinazoline ring system as well as the relative orientation difference of the two 2-methoxyethoxy side chains (Fig. 4).

The conformation of the 2-methoxyethoxy side chains can be defined from the torsion angles C—O—C—C, O—C—C—O, C—C—O—C and the conformation is anti (a)-gauche (g)-anti (a) for both C5 and C6 side chains. The main difference between the two rings and between the three structures is the change of signs in anti and gauge conformations. However, in the case of the erlotinib–EGFR kinase complex and erlotinib HCl structures, a significant difference is observed in the conformation of the side chains. The corresponding conformations are found to be (-)a-(-)g-(+)g and (-)a-(+)g-(-)a for erlotinib-EGFR kinase complex (+)a-(-)g-(-)a and (+)a-(-)a-(-)g for the erlotinib HCl.

For convenience, we denote the atoms N1/C1/N2/C2/C3/C8 and C3–C8 rings of the quinazoline rings as A and B, respectively, and the atoms C15–C20 of the ethynylphenyl ring as C.

In (I) and (III), three types of hydrogen bonds, viz N—H···O, O—H···O and O—H···N, are observed, while in (II), only one type of N—H···O hydrogen bonding is observed (Tables 2, 3, 4). In all three structures, hydrogen bonds and aromatic π-π stacking interactions play a key role in assembling the supramolecular structure.

In (I) the water molecule acts as both donor and acceptor (Table 2). As donor, it forms a hydrogen bond to the O3 of the 2-methoxyethoxy side chain and to N1 of the quinazoline ring of a second erlotinib molecule. As acceptor, it links to the atom N3 of a third erlotinib molecule. The combination of the first and third of these hydrogen bonds leads to the formation of a centrosymmetric tetramer which may be described in graph-set notation as R44(18) (Etter, 1990; Etter et al., 1990; Bernstein et al., 1995). The R44(18) tetramers are further linked by O—H···N hydrogen bonds, thereby leading to an infinite one-dimensional chain running along the a axis (Fig. 5). Intermolecular stacking via aromatic π-π interactions is also present between the B and C rings [centroid-to-centroid separation = 3.7381 (9) Å; symmetry code: 1 - x,1 -y,2 - z] and forms centrosymmetric dimers in (I).

In (II), cation-to-anion N—H···O hydrogen bonds stabilize the crystal structure (Table 3). The N1 of the erlotinib cation forms a hydrogen bond to O6 of the oxalate anion, while N3 links to O5 of a translation-related anion. This creates hydrogen-bonded columns along b including a R44(22) motif (Fig. 6). Face-to-face stacking interactions between adjacent symmetry-related quinazoline rings A and B [centroid-to-centroid separation = 3.7625 (14) Å; symmetry code: 1 - x,1 - y, -z] and between the quinazoline ring B and the ethynylphenyl ring C [centroid-to-centroid separation = 3.4637 (15) Å; symmetry code: 1 - x, 1 - y, -z] consolidate the supramolecular structure. Propagation of these two π-stacking interactions links the molecules into sheets in (II).

In (III), both the water molecules play a dual role as donor and acceptor (Table 4). The water molecule, O1W, as donor links the two O atoms of the methoxyethoxy side chains through intramolecular O—H···O hydrogen bonds and so forms an R22(13) motif. In its capacity as donor, the second water molecule, O2W, forms hydrogen bonds to O1W and to the carbonyl O atom of a fumaric acid molecule. In addition, O2W acts as acceptor in a hydrogen bond from N3 of the erlotinib molecule, analogous to the hydrogen bond observed in (I). In the erlotinib–EGFR kinase complex structure, the same N atom (N3) is also hydrogen bonded only with the water molecule. Thus, in (III), the water–water linkage interconnects the erlotinib molecules via O—H···O and O···H—N hydrogen bonds and leads to the formation of an R66(30) motif. Each R66(30) motif is arranged as a hexameric hydrogen-bonded network consisting of two sets of centrosymmetrically related erlotinib molecules and two sets of water–water linkages (Fig. 7). The fumaric acid lying across the centre of inversion forms a linear hydrogen-bonded trimer through an intramolecular O—H···N hydrogen bond with the two erlotinib molecules. In addition, it forms an O—H···O hydrogen bond with the second water molecule (O2W). Thus, the combination of these two O—H···N and O—H···O hydrogen bonds forms another set of hexameric hydrogen-bonded networks of R66(24) motif. The R66(30) and R66(24) motifs are arranged alternately and aggregate as infinite two-dimensional supramolecular hydrogen-bonded networks (Fig. 7).

In (III), the pairs of molecules are linked to centrosymmetric dimers similar to (I), by means of two aromatic ππ interactions, between ring A and its inversion-related ring A [centroid-to-centroid separation = 3.7249 (17) Å; symmetry code: -x,1 - y,1 - z] and between ring A and ring B [centroid-to-centroid separation = 3.6201 (16) Å; symmetry code: 1 - x,1 - y,1 - z]. In all three structures, weak C—H···O, C—H···N and C—H···π interactions are observed.

Related literature top

For related literature, see: Berman et al. (2000); Bernstein et al. (1995); Desiraju & Steiner (1999); Etter (1990); Etter, MacDonald & Bernstein (1990); Ghosh et al. (2001); Glusker (1998); Rusch et al. (1996); Selvanayagam et al. (2008); Sheldrick (2008); Stahly (2007); Stamos et al. (2002); Xia (2005); Yarden & Ullrich (1988).

Experimental top

To obtain crystals of (I) suitable for X-ray study, erlotinib (SMS Pharma Research Centre, Hyderabad) (40 mg) was dissolved in water (10 ml) and the solution allowed to evaporate slowly. Crystals of (II) and (III) were obtained by slow evaporation from the mixture of methanol (5 ml) and water (1 ml) with erlotinib (40 mg) and oxalic acid (10 mg) in (II) and with erlotinib (40 mg) and fumaric acid (120 mg) in (III).

Refinement top

All the N-bound H atoms of the erlotinib molecules [(I), (II) and (III)] were located in difference Fourier maps and their positions and isotropic displacement parameters were refined. The water H atoms of (I) and (III) were located in difference Fourier maps and their positions were refined. The isotropic displacement parameters of the water H atoms were fixed at 1.2 times the Ueq values of their parent O atoms. All other H atoms were located in a difference density map positioned geometrically and included as riding atoms, with C—H = 0.93–0.98 Å and Uiso(H) = 1.2Ueq(C). The site-occupancy factors of the disordered atoms C13/O2/C14 of (I) were refined to 0.554 (7) and 0.446 (7). The geometries about the disordered atoms were restrained with C12—C13 = C12—C131 = 1.52 (1) Å and C13—O2 = C131—O21 = O2—C14 = O21—C141 = 1.42 (1) Å. The atom C11 of (I) shows a large displacement parameter and the anisotropic displacement parameters of atoms C10/O4/C11 were restrained to be similar [SIMU instruction in SHELXL97 (Sheldrick, 2008)], and the direction of motion along the axis between these atoms was also restrained (DELU instruction in SHELXL97). In (III), the atoms O5/O6/C23/C24 of the hemifumaric acid molecule are disordered over two sites (O5/O6/C23/C24 and O51/O61/C231/C241) and the site-occupation factors refined to 0.55 (2) and 0.45 (2). The anisotropic displacement parameters of the major and minor components were restrained to be similar (SIMU instruction in SHELXL97), and the direction of motion along the axis between these atoms was also restrained (DELU instruction in SHELXL97). Distance restraints were also applied to the disordered components. The O-bound H atom of the fumaric acid was located in difference Fourier maps and found to be shared by both the disordered atoms O5 and O51. The positions and isotropic displacement parameter were refined. The methyl groups were allowed to rotate but not to tip.

Computing details top

For all compounds, data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT (Bruker, 2001); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg & Putz, 2005); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. A view of (I), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii. The dashed lines indicate the hydrogen bonds. The minor component of the disordered atoms C131/O21/C141 has been omitted for clarity.
[Figure 2] Fig. 2. A view of (II), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii. The dashed lines indicate the hydrogen bonds. [Symmetry code: (i) -x + 2, -y + 2, -z.]
[Figure 3] Fig. 3. A view of (III), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii. The minor component of the disordered O51/O61/C231/C241 of the hemifumaric acid molecule has been omitted for clarity. The dashed lines indicate the hydrogen bonds. [Symmetry code: (i) -x, -y, -z + 1.]
[Figure 4] Fig. 4. A superposition of the molecular conformations of erlotinib molecules. The overlay was made by making a least-squares fit through the quinazoline ring system of erlotinib–EGFR kinase complex (labelled 5). The labels and r.m.s deviations (Å) are as follows: erlotinib hydrate (I), 0.076; erlotinib hemioxalate (II), 0.087; erlotinib hemifumaric acid dihydrate (III), 0.07; erlotinib HCl, (labelled 4), 0.076.
[Figure 5] Fig. 5. A packing diagram for (I), viewed down the c axis, showing the centrosymmetric tetramer R44(18) ring motif. Hydrogen bonds are shown as dashed lines. H atoms not involved in hydrogen bonding and the minor component of the disordered atoms C131/O21/C141 have been omitted for clarity. Only atoms involved in the hydrogen bonding are labelled. [Symmetry codes: (i) -x + 2, -y + 1, -z + 2; (ii) x + 1, y, z.]
[Figure 6] Fig. 6. A packing diagram for (II), viewed through the a axis, showing centrosymmetric tetrameric [R44(22)] hydrogen-bonded columns. Hydrogen bonds are shown as dashed lines and H atoms not involved in hydrogen bonding have been omitted for clarity. Only atoms involved in the hydrogen bonding are labelled. [Symmetry codes: (i) x, y - 1, z.]
[Figure 7] Fig. 7. A partial packing view of (III), showing two hexameric [R66(30) and R66(24)] hydrogen-bonded networks. Hydrogen bonds are shown as dashed lines and H atoms not involved in hydrogen bonding and the minor component of the disordered O51/O61/C231/C241 of the hemifumaric acid molecule have been omitted for clarity. Only atoms involved in the hydrogen bonding are labelled. [Symmetry codes: (i) -x,1 - y,-z; (ii) 1 - x,1 - y,1 - z.]
(I) N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine monohydrate top
Crystal data top
C22H23N3O4·H2OZ = 2
Mr = 411.45F(000) = 436
Triclinic, P1Dx = 1.313 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 9.0227 (10) ÅCell parameters from 5228 reflections
b = 10.4548 (11) Åθ = 2.2–27.9°
c = 13.2014 (14) ŵ = 0.09 mm1
α = 98.705 (2)°T = 294 K
β = 108.738 (2)°Block, colorless
γ = 111.873 (2)°0.19 × 0.13 × 0.09 mm
V = 1041.05 (19) Å3
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
3169 reflections with I > 2σ(I)
Radiation source: sealed tubeRint = 0.017
Graphite monochromatorθmax = 25.0°, θmin = 2.2°
ω scanh = 1010
10097 measured reflectionsk = 1212
3666 independent reflectionsl = 1515
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)] = 0.043Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.120H atoms treated by a mixture of independent and constrained refinement
S = 1.03 w = 1/[σ2(Fo2) + (0.0652P)2 + 0.166P]
where P = (Fo2 + 2Fc2)/3
3666 reflections(Δ/σ)max = 0.001
311 parametersΔρmax = 0.18 e Å3
21 restraintsΔρmin = 0.28 e Å3
Crystal data top
C22H23N3O4·H2Oγ = 111.873 (2)°
Mr = 411.45V = 1041.05 (19) Å3
Triclinic, P1Z = 2
a = 9.0227 (10) ÅMo Kα radiation
b = 10.4548 (11) ŵ = 0.09 mm1
c = 13.2014 (14) ÅT = 294 K
α = 98.705 (2)°0.19 × 0.13 × 0.09 mm
β = 108.738 (2)°
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
3169 reflections with I > 2σ(I)
10097 measured reflectionsRint = 0.017
3666 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.04321 restraints
wR(F2) = 0.120H atoms treated by a mixture of independent and constrained refinement
S = 1.03Δρmax = 0.18 e Å3
3666 reflectionsΔρmin = 0.28 e Å3
311 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
C10.75210 (19)1.01314 (16)1.11192 (14)0.0571 (4)
H10.71621.08091.13450.068*
C20.98121 (17)0.96540 (14)1.11893 (11)0.0435 (3)
C30.85915 (16)0.82402 (14)1.04030 (11)0.0413 (3)
C40.90549 (17)0.72113 (14)0.99468 (11)0.0448 (3)
H41.02310.74351.01510.054*
C50.77919 (17)0.58952 (14)0.92095 (12)0.0458 (3)
C60.59847 (17)0.55081 (14)0.89195 (11)0.0450 (3)
C70.55111 (17)0.64950 (15)0.93433 (11)0.0467 (3)
H70.43320.62500.91480.056*
C80.68000 (17)0.78811 (14)1.00743 (11)0.0436 (3)
C90.95945 (19)0.52836 (17)0.84211 (14)0.0584 (4)
H9B1.05360.51980.89740.070*
H9A1.00070.62830.84220.070*
C100.9051 (3)0.4313 (2)0.72896 (16)0.0751 (5)
H10A0.80680.43660.67490.090*
H10B1.00110.46220.70580.090*
C110.7474 (4)0.1821 (3)0.6302 (2)0.1361 (11)
H11A0.72220.08850.64040.204*
H11B0.80310.19420.57910.204*
H11C0.64020.18990.60010.204*
C120.30426 (18)0.37191 (17)0.77667 (13)0.0591 (4)
H12A0.27530.43690.73810.071*
H12B0.26170.36790.83550.071*
C130.2314 (18)0.2233 (8)0.6960 (8)0.073 (3)0.554 (7)
H13A0.28690.16900.73220.087*0.554 (7)
H13B0.10660.17180.67570.087*0.554 (7)
O20.2608 (13)0.2329 (9)0.5980 (8)0.077 (2)0.554 (7)
C140.2189 (9)0.1003 (5)0.5236 (4)0.122 (2)0.554 (7)
H14A0.25810.11850.46540.183*0.554 (7)
H14B0.09430.04120.49070.183*0.554 (7)
H14C0.27570.05080.56420.183*0.554 (7)
C1310.196 (2)0.2216 (11)0.6928 (11)0.069 (3)0.446 (7)
H13C0.23030.15390.72430.083*0.446 (7)
H13D0.07290.19080.67670.083*0.446 (7)
O210.2208 (16)0.2218 (13)0.5925 (11)0.085 (3)0.446 (7)
C1410.3550 (8)0.1845 (7)0.5906 (5)0.0836 (18)0.446 (7)
H14D0.36730.18740.52130.125*0.446 (7)
H14E0.32570.08860.59660.125*0.446 (7)
H14F0.46330.25210.65260.125*0.446 (7)
C151.30051 (17)1.13446 (14)1.23772 (11)0.0449 (3)
C161.2899 (2)1.25678 (16)1.28597 (12)0.0535 (4)
H161.18141.25661.26840.064*
C171.4412 (2)1.37874 (17)1.36015 (13)0.0616 (4)
H171.43301.46041.39130.074*
C181.6036 (2)1.38200 (16)1.38890 (12)0.0602 (4)
H181.70371.46471.43940.072*
C191.61654 (18)1.26067 (16)1.34183 (12)0.0534 (4)
C201.46473 (18)1.13763 (15)1.26602 (12)0.0502 (3)
H201.47341.05661.23390.060*
C211.7847 (2)1.26054 (18)1.37171 (14)0.0641 (4)
C221.9222 (2)1.2602 (2)1.39920 (19)0.0876 (6)
H222.03091.26001.42090.105*
N10.62628 (15)0.88598 (13)1.04533 (11)0.0531 (3)
N20.92649 (15)1.05919 (13)1.15217 (11)0.0535 (3)
N31.15649 (14)1.00449 (13)1.15992 (10)0.0470 (3)
H3N1.1848 (19)0.9423 (17)1.1363 (13)0.050 (4)*
O10.48834 (12)0.41491 (10)0.82075 (8)0.0555 (3)
O30.81022 (14)0.48559 (11)0.86847 (11)0.0688 (3)
O40.8565 (2)0.28741 (14)0.73162 (11)0.0847 (4)
O1W1.32150 (16)0.80957 (14)1.09388 (13)0.0706 (4)
H1W1.316 (3)0.745 (3)1.120 (2)0.085*
H2W1.405 (3)0.828 (2)1.0738 (17)0.086*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0508 (8)0.0498 (8)0.0741 (10)0.0246 (7)0.0308 (8)0.0117 (7)
C20.0422 (7)0.0422 (7)0.0479 (7)0.0172 (6)0.0217 (6)0.0163 (6)
C30.0397 (7)0.0417 (7)0.0446 (7)0.0171 (6)0.0203 (6)0.0161 (6)
C40.0363 (7)0.0438 (7)0.0552 (8)0.0172 (6)0.0211 (6)0.0155 (6)
C50.0446 (7)0.0405 (7)0.0550 (8)0.0181 (6)0.0253 (6)0.0138 (6)
C60.0418 (7)0.0423 (7)0.0443 (7)0.0124 (6)0.0179 (6)0.0126 (6)
C70.0354 (7)0.0512 (8)0.0515 (8)0.0168 (6)0.0184 (6)0.0164 (6)
C80.0405 (7)0.0468 (7)0.0479 (7)0.0199 (6)0.0218 (6)0.0171 (6)
C90.0506 (8)0.0578 (9)0.0749 (10)0.0279 (7)0.0324 (8)0.0182 (8)
C100.0946 (13)0.0755 (11)0.0768 (11)0.0495 (10)0.0453 (10)0.0293 (9)
C110.178 (3)0.0878 (16)0.0848 (16)0.0264 (17)0.0309 (17)0.0140 (13)
C120.0414 (8)0.0585 (9)0.0571 (9)0.0083 (7)0.0145 (7)0.0145 (7)
C130.045 (5)0.059 (3)0.072 (4)0.003 (2)0.006 (2)0.018 (3)
O20.098 (5)0.057 (2)0.056 (3)0.028 (3)0.017 (3)0.0123 (19)
C140.164 (6)0.076 (3)0.094 (3)0.046 (3)0.035 (4)0.004 (3)
C1310.043 (5)0.060 (4)0.073 (5)0.006 (3)0.016 (3)0.000 (3)
O210.074 (4)0.098 (6)0.055 (3)0.041 (3)0.002 (2)0.000 (3)
C1410.086 (4)0.087 (4)0.075 (3)0.043 (3)0.030 (3)0.011 (3)
C150.0448 (7)0.0408 (7)0.0422 (7)0.0134 (6)0.0161 (6)0.0137 (6)
C160.0541 (8)0.0496 (8)0.0492 (8)0.0229 (7)0.0150 (7)0.0110 (6)
C170.0694 (10)0.0485 (8)0.0517 (8)0.0248 (8)0.0136 (7)0.0051 (7)
C180.0594 (9)0.0478 (8)0.0463 (8)0.0112 (7)0.0088 (7)0.0060 (6)
C190.0471 (8)0.0523 (8)0.0463 (8)0.0123 (6)0.0141 (6)0.0147 (6)
C200.0469 (8)0.0451 (8)0.0516 (8)0.0157 (6)0.0190 (6)0.0125 (6)
C210.0474 (9)0.0580 (9)0.0603 (9)0.0089 (7)0.0128 (7)0.0078 (7)
C220.0481 (10)0.0858 (14)0.0990 (15)0.0188 (9)0.0163 (10)0.0106 (11)
N10.0445 (6)0.0527 (7)0.0669 (8)0.0243 (6)0.0274 (6)0.0153 (6)
N20.0485 (7)0.0458 (7)0.0647 (8)0.0195 (5)0.0266 (6)0.0102 (6)
N30.0397 (6)0.0398 (6)0.0548 (7)0.0153 (5)0.0173 (5)0.0086 (5)
O10.0443 (5)0.0455 (5)0.0588 (6)0.0104 (4)0.0165 (5)0.0052 (4)
O30.0599 (7)0.0431 (6)0.1028 (9)0.0160 (5)0.0491 (6)0.0054 (5)
O40.1224 (11)0.0707 (8)0.0702 (8)0.0544 (8)0.0394 (7)0.0174 (6)
O1W0.0510 (7)0.0592 (7)0.1148 (10)0.0278 (6)0.0439 (7)0.0317 (7)
Geometric parameters (Å, º) top
C1—N11.3075 (19)C12—H12B0.9700
C1—N21.3457 (18)C13—O21.413 (7)
C1—H10.9300C13—H13A0.9700
C2—N21.3295 (18)C13—H13B0.9700
C2—N31.3647 (17)O2—C141.410 (8)
C2—C31.4364 (19)C14—H14A0.9600
C3—C81.4107 (18)C14—H14B0.9600
C3—C41.4127 (19)C14—H14C0.9600
C4—C51.3612 (19)C131—O211.413 (8)
C4—H40.9300C131—H13C0.9700
C5—O31.3647 (17)C131—H13D0.9700
C5—C61.4246 (18)O21—C1411.409 (9)
C6—O11.3540 (16)C141—H14D0.9600
C6—C71.367 (2)C141—H14E0.9600
C7—C81.408 (2)C141—H14F0.9600
C7—H70.9300C15—C161.391 (2)
C8—N11.3794 (18)C15—C201.393 (2)
C9—O31.4261 (18)C15—N31.4122 (17)
C9—C101.483 (2)C16—C171.384 (2)
C9—H9B0.9700C16—H160.9300
C9—H9A0.9700C17—C181.376 (2)
C10—O41.411 (2)C17—H170.9300
C10—H10A0.9700C18—C191.388 (2)
C10—H10B0.9700C18—H180.9300
C11—O41.368 (3)C19—C201.3962 (19)
C11—H11A0.9600C19—C211.440 (2)
C11—H11B0.9600C20—H200.9300
C11—H11C0.9600C21—C221.177 (2)
C12—O11.4293 (18)C22—H220.9300
C12—C131.506 (7)N3—H3N0.836 (16)
C12—C1311.511 (8)O1W—H1W0.80 (2)
C12—H12A0.9700O1W—H2W0.85 (2)
N1—C1—N2128.76 (13)C12—C13—H13A109.5
N1—C1—H1115.6O2—C13—H13B109.5
N2—C1—H1115.6C12—C13—H13B109.5
N2—C2—N3119.37 (12)H13A—C13—H13B108.1
N2—C2—C3121.15 (12)C14—O2—C13115.3 (6)
N3—C2—C3119.49 (12)O2—C14—H14A109.5
C8—C3—C4118.78 (12)O2—C14—H14B109.5
C8—C3—C2116.14 (12)H14A—C14—H14B109.5
C4—C3—C2125.08 (12)O2—C14—H14C109.5
C5—C4—C3120.43 (12)H14A—C14—H14C109.5
C5—C4—H4119.8H14B—C14—H14C109.5
C3—C4—H4119.8O21—C131—C12109.8 (10)
C4—C5—O3124.87 (12)O21—C131—H13C109.7
C4—C5—C6120.72 (12)C12—C131—H13C109.7
O3—C5—C6114.40 (12)O21—C131—H13D109.7
O1—C6—C7126.28 (12)C12—C131—H13D109.7
O1—C6—C5114.10 (12)H13C—C131—H13D108.2
C7—C6—C5119.61 (12)C141—O21—C131112.9 (11)
C6—C7—C8120.33 (12)O21—C141—H14D109.5
C6—C7—H7119.8O21—C141—H14E109.5
C8—C7—H7119.8H14D—C141—H14E109.5
N1—C8—C7118.42 (12)O21—C141—H14F109.5
N1—C8—C3121.56 (12)H14D—C141—H14F109.5
C7—C8—C3120.02 (12)H14E—C141—H14F109.5
O3—C9—C10107.48 (13)C16—C15—C20118.82 (13)
O3—C9—H9B110.2C16—C15—N3125.21 (13)
C10—C9—H9B110.2C20—C15—N3115.97 (12)
O3—C9—H9A110.2C17—C16—C15119.80 (14)
C10—C9—H9A110.2C17—C16—H16120.1
H9B—C9—H9A108.5C15—C16—H16120.1
O4—C10—C9109.79 (15)C18—C17—C16121.56 (15)
O4—C10—H10A109.7C18—C17—H17119.2
C9—C10—H10A109.7C16—C17—H17119.2
O4—C10—H10B109.7C17—C18—C19119.39 (14)
C9—C10—H10B109.7C17—C18—H18120.3
H10A—C10—H10B108.2C19—C18—H18120.3
O4—C11—H11A109.5C18—C19—C20119.46 (14)
O4—C11—H11B109.5C18—C19—C21120.49 (13)
H11A—C11—H11B109.5C20—C19—C21120.05 (14)
O4—C11—H11C109.5C15—C20—C19120.97 (14)
H11A—C11—H11C109.5C15—C20—H20119.5
H11B—C11—H11C109.5C19—C20—H20119.5
O1—C12—C13101.7 (6)C22—C21—C19178.02 (19)
O1—C12—C131113.2 (7)C21—C22—H22180.0
O1—C12—H12A111.4C1—N1—C8115.44 (12)
C13—C12—H12A111.4C2—N2—C1116.78 (12)
C131—C12—H12A106.4C2—N3—C15130.25 (12)
O1—C12—H12B111.4C2—N3—H3N116.0 (11)
C13—C12—H12B111.4C15—N3—H3N113.7 (11)
C131—C12—H12B104.8C6—O1—C12118.19 (12)
H12A—C12—H12B109.3C5—O3—C9119.26 (11)
O2—C13—C12110.8 (7)C11—O4—C10115.55 (17)
O2—C13—H13A109.5H1W—O1W—H2W106 (2)
N2—C2—C3—C84.29 (19)N3—C15—C16—C17179.07 (13)
N3—C2—C3—C8175.99 (11)C15—C16—C17—C180.8 (2)
N2—C2—C3—C4175.60 (12)C16—C17—C18—C190.5 (2)
N3—C2—C3—C44.1 (2)C17—C18—C19—C200.1 (2)
C8—C3—C4—C50.4 (2)C17—C18—C19—C21179.13 (14)
C2—C3—C4—C5179.68 (12)C16—C15—C20—C190.3 (2)
C3—C4—C5—O3176.88 (13)N3—C15—C20—C19179.78 (12)
C3—C4—C5—C62.6 (2)C18—C19—C20—C150.6 (2)
C4—C5—C6—O1177.87 (12)C21—C19—C20—C15178.70 (13)
O3—C5—C6—O12.63 (18)N2—C1—N1—C83.1 (2)
C4—C5—C6—C73.2 (2)C7—C8—N1—C1179.29 (13)
O3—C5—C6—C7176.27 (12)C3—C8—N1—C10.8 (2)
O1—C6—C7—C8179.58 (12)N3—C2—N2—C1177.87 (12)
C5—C6—C7—C80.8 (2)C3—C2—N2—C12.4 (2)
C6—C7—C8—N1177.91 (12)N1—C1—N2—C21.6 (2)
C6—C7—C8—C32.2 (2)N2—C2—N3—C151.0 (2)
C4—C3—C8—N1177.28 (12)C3—C2—N3—C15179.23 (12)
C2—C3—C8—N12.62 (19)C16—C15—N3—C23.3 (2)
C4—C3—C8—C72.80 (19)C20—C15—N3—C2177.24 (13)
C2—C3—C8—C7177.30 (11)C7—C6—O1—C125.8 (2)
O3—C9—C10—O463.80 (18)C5—C6—O1—C12172.97 (12)
O1—C12—C13—O274.6 (10)C13—C12—O1—C6175.3 (4)
C131—C12—C13—O2110 (5)C131—C12—O1—C6176.4 (6)
C12—C13—O2—C14171.8 (9)C4—C5—O3—C931.4 (2)
O1—C12—C131—O2170.2 (13)C6—C5—O3—C9148.11 (13)
C13—C12—C131—O2165 (4)C10—C9—O3—C5139.61 (15)
C12—C131—O21—C14192.9 (14)C9—C10—O4—C11157.4 (2)
C20—C15—C16—C170.3 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N3—H3N···O1W0.836 (16)2.290 (17)3.1123 (18)167.9 (14)
O1W—H1W···O3i0.80 (2)2.30 (2)3.0485 (18)156 (2)
O1W—H2W···N1ii0.85 (2)2.03 (2)2.8742 (18)173 (2)
C4—H4···O1W0.932.333.248 (2)171
C16—H16···N20.932.272.874 (2)122
C20—H20···O1W0.932.503.323 (2)148
C12—H12B···Cg2iii0.972.763.642 (2)151
Symmetry codes: (i) x+2, y+1, z+2; (ii) x+1, y, z; (iii) x+1, y+1, z+2.
(II) 4-amino-N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-1-ium hemioxalate top
Crystal data top
C22H24N3O4+·0.5C2O42Z = 2
Mr = 438.45F(000) = 462
Triclinic, P1Dx = 1.358 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 7.6285 (8) ÅCell parameters from 2417 reflections
b = 10.2252 (10) Åθ = 2.6–24.9°
c = 14.6525 (14) ŵ = 0.10 mm1
α = 86.076 (2)°T = 294 K
β = 84.925 (2)°Block, colorless
γ = 70.559 (2)°0.17 × 0.09 × 0.06 mm
V = 1072.62 (18) Å3
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
2996 reflections with I > 2σ(I)
Radiation source: sealed tubeRint = 0.032
Graphite monochromatorθmax = 25.0°, θmin = 2.1°
ω scanh = 99
10367 measured reflectionsk = 1212
3758 independent reflectionsl = 1717
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)] = 0.067Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.142H atoms treated by a mixture of independent and constrained refinement
S = 1.17 w = 1/[σ2(Fo2) + (0.0518P)2 + 0.3741P]
where P = (Fo2 + 2Fc2)/3
3758 reflections(Δ/σ)max < 0.001
299 parametersΔρmax = 0.25 e Å3
0 restraintsΔρmin = 0.18 e Å3
Crystal data top
C22H24N3O4+·0.5C2O42γ = 70.559 (2)°
Mr = 438.45V = 1072.62 (18) Å3
Triclinic, P1Z = 2
a = 7.6285 (8) ÅMo Kα radiation
b = 10.2252 (10) ŵ = 0.10 mm1
c = 14.6525 (14) ÅT = 294 K
α = 86.076 (2)°0.17 × 0.09 × 0.06 mm
β = 84.925 (2)°
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
2996 reflections with I > 2σ(I)
10367 measured reflectionsRint = 0.032
3758 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0670 restraints
wR(F2) = 0.142H atoms treated by a mixture of independent and constrained refinement
S = 1.17Δρmax = 0.25 e Å3
3758 reflectionsΔρmin = 0.18 e Å3
299 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.6538 (4)0.7816 (3)0.07682 (19)0.0429 (7)
H10.61120.86430.11140.051*
C20.6954 (3)0.5508 (2)0.05991 (16)0.0310 (6)
C30.7603 (3)0.5476 (2)0.02983 (16)0.0309 (6)
C40.8042 (3)0.4321 (2)0.09165 (17)0.0335 (6)
H40.79730.34840.07400.040*
C50.8569 (3)0.4401 (2)0.17697 (17)0.0338 (6)
C60.8739 (3)0.5672 (2)0.20392 (16)0.0330 (6)
C70.8363 (3)0.6784 (2)0.14350 (17)0.0335 (6)
H70.85140.76020.15970.040*
C80.7758 (3)0.6712 (2)0.05782 (16)0.0312 (6)
C90.8641 (4)0.2097 (3)0.21985 (19)0.0493 (7)
H9A0.95950.16210.17400.059*
H9B0.74370.23190.19460.059*
C100.8716 (5)0.1183 (3)0.3037 (2)0.0562 (8)
H10A0.88140.02590.28690.067*
H10B0.98040.11140.33580.067*
C110.7111 (6)0.0936 (4)0.4435 (2)0.0849 (12)
H11A0.72000.00100.42990.127*
H11B0.59820.13480.48050.127*
H11C0.81610.09060.47610.127*
C120.9330 (4)0.6951 (3)0.31939 (18)0.0433 (7)
H12A0.81420.76750.31170.052*
H12B1.02830.72140.28200.052*
C130.9761 (4)0.6811 (3)0.41766 (19)0.0519 (8)
H13A1.07550.59440.42850.062*
H13B1.01800.75660.43200.062*
C140.8367 (6)0.7054 (4)0.5665 (2)0.0825 (11)
H14A0.95380.64300.58540.124*
H14B0.73680.68860.60460.124*
H14C0.83240.79940.57210.124*
C150.6377 (3)0.4083 (2)0.17937 (16)0.0323 (6)
C160.5920 (4)0.5041 (3)0.25221 (18)0.0425 (7)
H160.59710.59300.24760.051*
C170.5388 (4)0.4675 (3)0.33159 (19)0.0492 (7)
H170.50540.53320.37970.059*
C180.5342 (4)0.3361 (3)0.34098 (18)0.0465 (7)
H180.49890.31280.39510.056*
C190.5824 (3)0.2384 (3)0.26931 (18)0.0390 (6)
C200.6329 (3)0.2752 (3)0.18822 (17)0.0369 (6)
H200.66360.21020.13960.044*
C210.5722 (4)0.1013 (3)0.27670 (19)0.0480 (7)
C220.5587 (5)0.0077 (4)0.2842 (2)0.0683 (10)
H220.54790.09460.29020.082*
N10.7260 (3)0.7866 (2)0.00035 (15)0.0364 (5)
H1N0.750 (4)0.871 (3)0.0137 (19)0.064 (9)*
N20.6354 (3)0.6701 (2)0.10989 (14)0.0404 (5)
N30.6931 (3)0.4331 (2)0.09420 (14)0.0329 (5)
H3N0.745 (3)0.356 (3)0.0617 (16)0.037 (7)*
O10.9253 (2)0.56607 (17)0.29002 (11)0.0401 (4)
O20.8179 (3)0.6836 (2)0.47428 (13)0.0625 (6)
O30.8932 (3)0.33528 (17)0.24216 (12)0.0445 (5)
O40.7096 (3)0.1732 (2)0.36128 (14)0.0647 (6)
C230.9071 (3)1.0604 (2)0.00605 (17)0.0339 (6)
O50.9188 (2)1.17606 (16)0.02807 (13)0.0469 (5)
O60.7588 (3)1.03374 (18)0.00793 (16)0.0617 (6)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0474 (17)0.0312 (14)0.0486 (17)0.0109 (12)0.0094 (14)0.0062 (12)
C20.0231 (12)0.0300 (13)0.0387 (14)0.0081 (10)0.0013 (10)0.0003 (11)
C30.0230 (13)0.0309 (13)0.0366 (14)0.0072 (10)0.0032 (10)0.0013 (11)
C40.0332 (14)0.0274 (13)0.0404 (15)0.0107 (11)0.0003 (11)0.0035 (11)
C50.0328 (14)0.0314 (13)0.0363 (15)0.0108 (11)0.0006 (11)0.0037 (11)
C60.0263 (13)0.0371 (14)0.0360 (14)0.0115 (11)0.0014 (11)0.0041 (11)
C70.0343 (14)0.0282 (13)0.0413 (15)0.0151 (11)0.0007 (11)0.0046 (11)
C80.0273 (13)0.0284 (13)0.0371 (14)0.0094 (10)0.0027 (11)0.0014 (11)
C90.070 (2)0.0324 (15)0.0459 (17)0.0167 (14)0.0061 (15)0.0009 (12)
C100.070 (2)0.0383 (16)0.062 (2)0.0195 (15)0.0141 (17)0.0081 (14)
C110.117 (3)0.086 (3)0.058 (2)0.045 (3)0.005 (2)0.010 (2)
C120.0415 (16)0.0432 (16)0.0482 (17)0.0168 (13)0.0011 (13)0.0103 (13)
C130.0465 (18)0.0565 (19)0.0548 (19)0.0160 (15)0.0109 (15)0.0132 (15)
C140.126 (3)0.082 (3)0.045 (2)0.042 (2)0.003 (2)0.0068 (18)
C150.0231 (13)0.0347 (14)0.0367 (14)0.0064 (11)0.0011 (10)0.0053 (11)
C160.0465 (16)0.0375 (15)0.0413 (16)0.0109 (13)0.0021 (13)0.0028 (12)
C170.0551 (18)0.0502 (18)0.0370 (16)0.0102 (14)0.0058 (13)0.0010 (13)
C180.0448 (17)0.0603 (19)0.0342 (15)0.0150 (14)0.0035 (12)0.0098 (14)
C190.0323 (14)0.0446 (16)0.0406 (15)0.0123 (12)0.0002 (12)0.0106 (13)
C200.0297 (14)0.0365 (14)0.0423 (15)0.0089 (11)0.0009 (11)0.0003 (11)
C210.0509 (18)0.0528 (18)0.0434 (16)0.0188 (15)0.0066 (13)0.0102 (14)
C220.092 (3)0.053 (2)0.070 (2)0.0324 (19)0.0143 (19)0.0149 (17)
N10.0379 (13)0.0296 (12)0.0441 (13)0.0141 (10)0.0060 (10)0.0022 (10)
N20.0453 (13)0.0320 (12)0.0436 (13)0.0113 (10)0.0108 (10)0.0027 (10)
N30.0324 (12)0.0278 (11)0.0365 (12)0.0069 (9)0.0055 (9)0.0001 (10)
O10.0474 (11)0.0379 (10)0.0377 (10)0.0160 (8)0.0088 (8)0.0016 (8)
O20.0662 (14)0.0881 (16)0.0384 (12)0.0310 (12)0.0020 (10)0.0104 (11)
O30.0583 (12)0.0347 (10)0.0435 (11)0.0183 (9)0.0126 (9)0.0049 (8)
O40.0787 (16)0.0508 (13)0.0622 (14)0.0222 (12)0.0049 (12)0.0060 (11)
C230.0392 (15)0.0242 (13)0.0403 (15)0.0107 (11)0.0093 (12)0.0057 (11)
O50.0462 (11)0.0228 (9)0.0715 (14)0.0099 (8)0.0153 (9)0.0056 (8)
O60.0334 (11)0.0325 (11)0.1179 (19)0.0099 (9)0.0049 (11)0.0014 (11)
Geometric parameters (Å, º) top
C1—N11.303 (3)C12—C131.492 (4)
C1—N21.322 (3)C12—H12A0.9700
C1—H10.9300C12—H12B0.9700
C2—N31.341 (3)C13—O21.396 (3)
C2—N21.342 (3)C13—H13A0.9700
C2—C31.440 (3)C13—H13B0.9700
C3—C81.400 (3)C14—O21.412 (3)
C3—C41.404 (3)C14—H14A0.9600
C4—C51.362 (3)C14—H14B0.9600
C4—H40.9300C14—H14C0.9600
C5—O31.359 (3)C15—C161.384 (3)
C5—C61.433 (3)C15—C201.388 (3)
C6—O11.352 (3)C15—N31.417 (3)
C6—C71.360 (3)C16—C171.379 (4)
C7—C81.390 (3)C16—H160.9300
C7—H70.9300C17—C181.373 (4)
C8—N11.372 (3)C17—H170.9300
C9—O31.437 (3)C18—C191.384 (4)
C9—C101.486 (4)C18—H180.9300
C9—H9A0.9700C19—C201.393 (3)
C9—H9B0.9700C19—C211.442 (4)
C10—O41.404 (4)C20—H200.9300
C10—H10A0.9700C21—C221.166 (4)
C10—H10B0.9700C22—H220.9300
C11—O41.405 (4)N1—H1N0.98 (3)
C11—H11A0.9600N3—H3N0.88 (3)
C11—H11B0.9600C23—O51.235 (3)
C11—H11C0.9600C23—O61.246 (3)
C12—O11.437 (3)C23—C23i1.554 (5)
N1—C1—N2126.1 (2)H12A—C12—H12B108.2
N1—C1—H1116.9O2—C13—C12110.2 (2)
N2—C1—H1116.9O2—C13—H13A109.6
N3—C2—N2119.1 (2)C12—C13—H13A109.6
N3—C2—C3119.8 (2)O2—C13—H13B109.6
N2—C2—C3121.1 (2)C12—C13—H13B109.6
C8—C3—C4117.9 (2)H13A—C13—H13B108.1
C8—C3—C2116.8 (2)O2—C14—H14A109.5
C4—C3—C2125.3 (2)O2—C14—H14B109.5
C5—C4—C3121.3 (2)H14A—C14—H14B109.5
C5—C4—H4119.3O2—C14—H14C109.5
C3—C4—H4119.3H14A—C14—H14C109.5
O3—C5—C4124.9 (2)H14B—C14—H14C109.5
O3—C5—C6115.2 (2)C16—C15—C20119.2 (2)
C4—C5—C6119.8 (2)C16—C15—N3125.3 (2)
O1—C6—C7125.1 (2)C20—C15—N3115.4 (2)
O1—C6—C5115.8 (2)C17—C16—C15119.9 (3)
C7—C6—C5119.1 (2)C17—C16—H16120.1
C6—C7—C8120.8 (2)C15—C16—H16120.1
C6—C7—H7119.6C18—C17—C16121.2 (3)
C8—C7—H7119.6C18—C17—H17119.4
N1—C8—C7120.5 (2)C16—C17—H17119.4
N1—C8—C3118.6 (2)C17—C18—C19119.6 (2)
C7—C8—C3120.9 (2)C17—C18—H18120.2
O3—C9—C10109.7 (2)C19—C18—H18120.2
O3—C9—H9A109.7C18—C19—C20119.6 (2)
C10—C9—H9A109.7C18—C19—C21120.4 (2)
O3—C9—H9B109.7C20—C19—C21120.0 (2)
C10—C9—H9B109.7C15—C20—C19120.5 (2)
H9A—C9—H9B108.2C15—C20—H20119.7
O4—C10—C9109.6 (2)C19—C20—H20119.7
O4—C10—H10A109.8C22—C21—C19177.7 (3)
C9—C10—H10A109.8C21—C22—H22180.0
O4—C10—H10B109.8C1—N1—C8119.7 (2)
C9—C10—H10B109.8C1—N1—H1N119.6 (17)
H10A—C10—H10B108.2C8—N1—H1N120.6 (17)
O4—C11—H11A109.5C1—N2—C2117.2 (2)
O4—C11—H11B109.5C2—N3—C15130.9 (2)
H11A—C11—H11B109.5C2—N3—H3N116.0 (16)
O4—C11—H11C109.5C15—N3—H3N112.8 (16)
H11A—C11—H11C109.5C6—O1—C12116.21 (19)
H11B—C11—H11C109.5C13—O2—C14112.2 (2)
O1—C12—C13110.1 (2)C5—O3—C9116.67 (19)
O1—C12—H12A109.6C10—O4—C11112.4 (3)
C13—C12—H12A109.6O5—C23—O6125.2 (2)
O1—C12—H12B109.6O5—C23—C23i116.8 (3)
C13—C12—H12B109.6O6—C23—C23i118.0 (3)
N3—C2—C3—C8174.1 (2)C16—C17—C18—C190.5 (4)
N2—C2—C3—C86.4 (3)C17—C18—C19—C200.7 (4)
N3—C2—C3—C47.6 (3)C17—C18—C19—C21177.9 (3)
N2—C2—C3—C4171.9 (2)C16—C15—C20—C190.1 (4)
C8—C3—C4—C51.3 (3)N3—C15—C20—C19179.3 (2)
C2—C3—C4—C5177.0 (2)C18—C19—C20—C150.9 (4)
C3—C4—C5—O3176.8 (2)C21—C19—C20—C15178.1 (2)
C3—C4—C5—C62.0 (4)N2—C1—N1—C85.9 (4)
O3—C5—C6—O10.6 (3)C7—C8—N1—C1173.9 (2)
C4—C5—C6—O1179.5 (2)C3—C8—N1—C14.7 (3)
O3—C5—C6—C7178.7 (2)N1—C1—N2—C20.5 (4)
C4—C5—C6—C70.2 (3)N3—C2—N2—C1174.7 (2)
O1—C6—C7—C8176.9 (2)C3—C2—N2—C15.8 (3)
C5—C6—C7—C82.3 (3)N2—C2—N3—C150.8 (4)
C6—C7—C8—N1175.5 (2)C3—C2—N3—C15179.7 (2)
C6—C7—C8—C33.1 (3)C16—C15—N3—C28.2 (4)
C4—C3—C8—N1177.4 (2)C20—C15—N3—C2172.7 (2)
C2—C3—C8—N11.1 (3)C7—C6—O1—C122.5 (3)
C4—C3—C8—C71.2 (3)C5—C6—O1—C12176.7 (2)
C2—C3—C8—C7179.7 (2)C13—C12—O1—C6175.3 (2)
O3—C9—C10—O472.7 (3)C12—C13—O2—C14165.2 (3)
O1—C12—C13—O276.5 (3)C4—C5—O3—C93.3 (4)
C20—C15—C16—C171.3 (4)C6—C5—O3—C9175.5 (2)
N3—C15—C16—C17179.6 (2)C10—C9—O3—C5168.3 (2)
C15—C16—C17—C181.5 (4)C9—C10—O4—C11178.0 (3)
Symmetry code: (i) x+2, y+2, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1N···O60.98 (3)1.68 (3)2.633 (3)163 (3)
N3—H3N···O5ii0.88 (3)1.94 (3)2.783 (3)160 (2)
C4—H4···O5ii0.932.293.087 (3)144
C16—H16···N20.932.292.885 (3)121
C20—H20···O5ii0.932.573.225 (3)128
C12—H12B···Cg3iii0.972.773.907 (3)160
Symmetry codes: (ii) x, y1, z; (iii) x, y+1, z+1.
(III) N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine fumaric acid hemisolvate dihydrate top
Crystal data top
C22H23N3O4·0.5C4H4O4·2H2OZ = 2
Mr = 487.50F(000) = 516
Triclinic, P1Dx = 1.305 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 7.967 (2) ÅCell parameters from 3735 reflections
b = 13.248 (4) Åθ = 2.7–25.4°
c = 13.745 (4) ŵ = 0.10 mm1
α = 108.916 (5)°T = 294 K
β = 106.673 (5)°Needle, colorless
γ = 101.909 (5)°0.18 × 0.16 × 0.11 mm
V = 1240.9 (6) Å3
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
3501 reflections with I > 2σ(I)
Radiation source: sealed tubeRint = 0.023
Graphite monochromatorθmax = 25.0°, θmin = 1.7°
ω scanh = 99
12036 measured reflectionsk = 1515
4364 independent reflectionsl = 1616
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)] = 0.054Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.140H atoms treated by a mixture of independent and constrained refinement
S = 1.08 w = 1/[σ2(Fo2) + (0.0633P)2 + 0.2675P]
where P = (Fo2 + 2Fc2)/3
4364 reflections(Δ/σ)max < 0.001
379 parametersΔρmax = 0.27 e Å3
56 restraintsΔρmin = 0.15 e Å3
Crystal data top
C22H23N3O4·0.5C4H4O4·2H2Oγ = 101.909 (5)°
Mr = 487.50V = 1240.9 (6) Å3
Triclinic, P1Z = 2
a = 7.967 (2) ÅMo Kα radiation
b = 13.248 (4) ŵ = 0.10 mm1
c = 13.745 (4) ÅT = 294 K
α = 108.916 (5)°0.18 × 0.16 × 0.11 mm
β = 106.673 (5)°
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
3501 reflections with I > 2σ(I)
12036 measured reflectionsRint = 0.023
4364 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.05456 restraints
wR(F2) = 0.140H atoms treated by a mixture of independent and constrained refinement
S = 1.08Δρmax = 0.27 e Å3
4364 reflectionsΔρmin = 0.15 e Å3
379 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
C10.2800 (3)0.44849 (18)0.56122 (17)0.0551 (5)
H10.32650.42600.61790.066*
C20.3112 (3)0.58402 (16)0.49437 (15)0.0484 (5)
C30.1450 (3)0.51298 (16)0.39735 (15)0.0458 (4)
C40.0631 (3)0.54320 (16)0.31014 (16)0.0496 (5)
H40.11940.61300.31200.060*
C50.0975 (3)0.47109 (16)0.22336 (16)0.0476 (5)
C60.1837 (3)0.36345 (16)0.21897 (15)0.0467 (5)
C70.1073 (3)0.33366 (16)0.30337 (16)0.0492 (5)
H70.16440.26380.30120.059*
C80.0572 (3)0.40835 (16)0.39349 (15)0.0458 (4)
C120.4317 (3)0.18723 (17)0.11728 (17)0.0555 (5)
H12A0.47330.19320.17810.067*
H12B0.34680.14430.11970.067*
C130.5933 (3)0.12983 (18)0.00898 (18)0.0593 (5)
H13A0.66990.06020.00480.071*
H13B0.66830.17820.00240.071*
C140.6716 (4)0.0597 (3)0.1849 (2)0.0907 (8)
H14A0.76140.00650.19340.136*
H14B0.62030.03970.24080.136*
H14C0.73050.11450.19280.136*
C90.1095 (3)0.59846 (18)0.13531 (18)0.0638 (6)
H9A0.01110.60380.13070.077*
H9B0.09320.65990.20300.077*
C100.2369 (3)0.6057 (2)0.03653 (19)0.0663 (6)
H10A0.35870.59670.03990.080*
H10B0.19000.67920.03640.080*
C110.3634 (4)0.5249 (2)0.1587 (2)0.0797 (7)
H11A0.48370.52240.15690.120*
H11B0.37600.46130.22230.120*
H11C0.30720.59360.16360.120*
C150.5458 (3)0.77727 (17)0.59997 (17)0.0553 (5)
C160.5613 (3)0.88594 (19)0.6070 (2)0.0713 (6)
H160.47970.89640.55040.086*
C170.6960 (4)0.9783 (2)0.6969 (2)0.0823 (8)
H170.70521.05060.70040.099*
C180.8174 (3)0.9643 (2)0.7817 (2)0.0756 (7)
H180.90701.02700.84280.091*
C190.8060 (3)0.85712 (19)0.77568 (17)0.0593 (6)
C200.6707 (3)0.76300 (18)0.68390 (16)0.0543 (5)
H200.66460.69060.67920.065*
C210.9283 (3)0.8393 (2)0.86379 (19)0.0658 (6)
C221.0233 (4)0.8218 (2)0.9342 (2)0.0820 (8)
H221.09900.80780.99030.098*
N10.1286 (2)0.37666 (14)0.47802 (13)0.0524 (4)
N20.3760 (2)0.55060 (14)0.57453 (13)0.0552 (4)
N30.4026 (3)0.68781 (15)0.50581 (15)0.0588 (5)
O10.34075 (18)0.29763 (11)0.12739 (11)0.0546 (4)
O20.5279 (2)0.10611 (14)0.07815 (12)0.0694 (4)
O30.19004 (18)0.49268 (11)0.13647 (11)0.0571 (4)
O40.2505 (2)0.52116 (15)0.06071 (13)0.0739 (5)
H3N0.366 (3)0.7032 (18)0.4514 (18)0.058 (6)*
O50.049 (2)0.1910 (14)0.4751 (14)0.094 (3)0.55 (2)
O60.210 (2)0.2101 (11)0.6014 (15)0.115 (4)0.55 (2)
C230.0506 (17)0.1556 (12)0.5382 (14)0.080 (3)0.55 (2)
C240.0502 (17)0.0355 (9)0.5190 (15)0.095 (3)0.55 (2)
H240.15880.01240.53030.114*0.55 (2)
O510.003 (3)0.1757 (14)0.4677 (15)0.092 (4)0.45 (2)
O610.233 (3)0.2406 (13)0.6283 (14)0.105 (3)0.45 (2)
C2310.108 (3)0.1610 (13)0.5486 (17)0.104 (7)0.45 (2)
C2410.057 (4)0.0461 (8)0.5511 (7)0.129 (6)0.45 (2)
H2410.09860.03650.61690.155*0.45 (2)
H5O0.033 (5)0.256 (3)0.476 (3)0.137 (13)*
O1W0.2816 (3)0.2842 (2)0.09821 (16)0.0854 (6)
H1W0.353 (5)0.249 (3)0.078 (3)0.102*
H2W0.279 (5)0.352 (3)0.074 (3)0.103*
O2W0.4029 (4)0.77270 (19)0.3289 (2)0.0933 (7)
H3W0.361 (5)0.753 (3)0.260 (3)0.112*
H4W0.518 (7)0.779 (4)0.347 (4)0.119*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0630 (13)0.0609 (13)0.0453 (11)0.0244 (11)0.0190 (10)0.0256 (10)
C20.0539 (11)0.0511 (12)0.0428 (11)0.0214 (9)0.0208 (9)0.0176 (9)
C30.0484 (11)0.0500 (11)0.0422 (10)0.0201 (9)0.0209 (9)0.0174 (9)
C40.0526 (11)0.0478 (11)0.0495 (11)0.0138 (9)0.0203 (10)0.0222 (9)
C50.0471 (11)0.0554 (12)0.0457 (11)0.0196 (9)0.0187 (9)0.0247 (9)
C60.0467 (11)0.0503 (11)0.0452 (11)0.0158 (9)0.0211 (9)0.0189 (9)
C70.0553 (12)0.0469 (11)0.0497 (11)0.0152 (9)0.0242 (10)0.0225 (9)
C80.0519 (11)0.0493 (11)0.0426 (10)0.0217 (9)0.0223 (9)0.0198 (9)
C120.0537 (12)0.0560 (12)0.0600 (13)0.0093 (10)0.0269 (10)0.0285 (10)
C130.0469 (11)0.0598 (13)0.0688 (14)0.0091 (10)0.0239 (11)0.0271 (11)
C140.0785 (18)0.104 (2)0.0630 (16)0.0096 (15)0.0093 (14)0.0296 (15)
C90.0653 (14)0.0587 (13)0.0627 (13)0.0109 (11)0.0137 (11)0.0345 (11)
C100.0708 (15)0.0618 (13)0.0706 (15)0.0224 (11)0.0218 (12)0.0366 (12)
C110.0805 (17)0.107 (2)0.0630 (15)0.0438 (15)0.0219 (13)0.0458 (15)
C150.0542 (12)0.0520 (12)0.0510 (12)0.0145 (10)0.0187 (10)0.0136 (10)
C160.0695 (15)0.0585 (14)0.0743 (16)0.0208 (12)0.0169 (13)0.0224 (12)
C170.0828 (18)0.0485 (13)0.095 (2)0.0167 (13)0.0241 (16)0.0156 (13)
C180.0623 (14)0.0619 (15)0.0718 (16)0.0106 (12)0.0183 (13)0.0025 (12)
C190.0483 (12)0.0657 (14)0.0522 (12)0.0146 (10)0.0218 (10)0.0105 (11)
C200.0514 (11)0.0555 (12)0.0497 (12)0.0161 (10)0.0201 (10)0.0141 (10)
C210.0469 (12)0.0807 (16)0.0489 (13)0.0126 (11)0.0174 (11)0.0074 (12)
C220.0618 (15)0.114 (2)0.0540 (14)0.0308 (15)0.0166 (12)0.0181 (14)
N10.0596 (10)0.0552 (10)0.0442 (9)0.0203 (8)0.0181 (8)0.0231 (8)
N20.0586 (10)0.0576 (11)0.0462 (9)0.0194 (9)0.0154 (8)0.0215 (8)
N30.0646 (12)0.0521 (10)0.0475 (11)0.0115 (9)0.0093 (9)0.0210 (9)
O10.0493 (8)0.0536 (8)0.0518 (8)0.0082 (6)0.0115 (7)0.0231 (7)
O20.0530 (8)0.0858 (11)0.0544 (9)0.0067 (8)0.0168 (7)0.0240 (8)
O30.0521 (8)0.0590 (9)0.0561 (8)0.0101 (7)0.0111 (7)0.0319 (7)
O40.0813 (11)0.0913 (12)0.0623 (10)0.0456 (9)0.0227 (8)0.0407 (9)
O50.079 (5)0.082 (5)0.113 (5)0.011 (3)0.021 (3)0.056 (4)
O60.117 (5)0.051 (6)0.128 (11)0.007 (4)0.010 (5)0.039 (6)
C230.088 (5)0.068 (4)0.092 (7)0.019 (3)0.037 (4)0.045 (5)
C240.077 (5)0.071 (5)0.143 (9)0.019 (4)0.043 (5)0.052 (6)
O510.089 (9)0.061 (5)0.090 (5)0.010 (5)0.006 (5)0.036 (4)
O610.144 (8)0.058 (6)0.075 (5)0.013 (5)0.001 (4)0.029 (5)
C2310.130 (13)0.060 (5)0.086 (7)0.001 (7)0.009 (8)0.035 (5)
C2410.177 (15)0.067 (5)0.075 (5)0.015 (7)0.015 (6)0.034 (5)
O1W0.0921 (14)0.0888 (15)0.0783 (12)0.0142 (12)0.0415 (11)0.0397 (11)
O2W0.1131 (19)0.0915 (14)0.0732 (14)0.0204 (12)0.0319 (13)0.0427 (12)
Geometric parameters (Å, º) top
C1—N11.303 (3)C11—O41.411 (3)
C1—N21.334 (3)C11—H11A0.9600
C1—H10.9300C11—H11B0.9600
C2—N21.327 (2)C11—H11C0.9600
C2—N31.351 (3)C15—C201.385 (3)
C2—C31.441 (3)C15—C161.388 (3)
C3—C81.394 (3)C15—N31.408 (3)
C3—C41.412 (3)C16—C171.376 (3)
C4—C51.361 (3)C16—H160.9300
C4—H40.9300C17—C181.376 (3)
C5—O31.362 (2)C17—H170.9300
C5—C61.423 (3)C18—C191.377 (3)
C6—O11.358 (2)C18—H180.9300
C6—C71.365 (3)C19—C201.397 (3)
C7—C81.403 (3)C19—C211.441 (3)
C7—H70.9300C20—H200.9300
C8—N11.373 (2)C21—C221.166 (3)
C12—O11.434 (2)C22—H220.9300
C12—C131.488 (3)N3—H3N0.83 (2)
C12—H12A0.9700O5—C231.273 (11)
C12—H12B0.9700O5—H5O0.96 (4)
C13—O21.409 (3)O6—C231.214 (11)
C13—H13A0.9700C23—C241.525 (11)
C13—H13B0.9700C24—C24i1.424 (13)
C14—O21.415 (3)C24—H240.9300
C14—H14A0.9600O51—C2311.303 (13)
C14—H14B0.9600O51—H5O1.01 (4)
C14—H14C0.9600O61—C2311.223 (14)
C9—O31.423 (2)C231—C2411.507 (13)
C9—C101.489 (3)C241—C241i1.409 (16)
C9—H9A0.9700C241—H2410.9300
C9—H9B0.9700O1W—H1W0.83 (4)
C10—O41.395 (3)O1W—H2W0.85 (4)
C10—H10A0.9700O2W—H3W0.83 (4)
C10—H10B0.9700O2W—H4W0.86 (5)
N1—C1—N2127.57 (18)H10A—C10—H10B108.2
N1—C1—H1116.2O4—C11—H11A109.5
N2—C1—H1116.2O4—C11—H11B109.5
N2—C2—N3118.73 (18)H11A—C11—H11B109.5
N2—C2—C3121.38 (18)O4—C11—H11C109.5
N3—C2—C3119.88 (17)H11A—C11—H11C109.5
C8—C3—C4118.71 (17)H11B—C11—H11C109.5
C8—C3—C2116.10 (17)C20—C15—C16118.9 (2)
C4—C3—C2125.14 (18)C20—C15—N3124.16 (19)
C5—C4—C3120.65 (18)C16—C15—N3116.9 (2)
C5—C4—H4119.7C17—C16—C15120.7 (2)
C3—C4—H4119.7C17—C16—H16119.6
C4—C5—O3125.43 (18)C15—C16—H16119.6
C4—C5—C6120.17 (17)C16—C17—C18120.4 (2)
O3—C5—C6114.40 (16)C16—C17—H17119.8
O1—C6—C7125.14 (17)C18—C17—H17119.8
O1—C6—C5115.04 (16)C17—C18—C19119.8 (2)
C7—C6—C5119.82 (17)C17—C18—H18120.1
C6—C7—C8120.08 (17)C19—C18—H18120.1
C6—C7—H7120.0C18—C19—C20120.0 (2)
C8—C7—H7120.0C18—C19—C21121.4 (2)
N1—C8—C3120.83 (17)C20—C19—C21118.7 (2)
N1—C8—C7118.63 (17)C15—C20—C19120.2 (2)
C3—C8—C7120.54 (17)C15—C20—H20119.9
O1—C12—C13107.70 (16)C19—C20—H20119.9
O1—C12—H12A110.2C22—C21—C19177.9 (3)
C13—C12—H12A110.2C21—C22—H22180.0
O1—C12—H12B110.2C1—N1—C8117.16 (17)
C13—C12—H12B110.2C2—N2—C1116.97 (17)
H12A—C12—H12B108.5C2—N3—C15129.22 (19)
O2—C13—C12109.01 (16)C2—N3—H3N116.3 (15)
O2—C13—H13A109.9C15—N3—H3N114.3 (15)
C12—C13—H13A109.9C6—O1—C12117.56 (15)
O2—C13—H13B109.9C13—O2—C14113.15 (18)
C12—C13—H13B109.9C5—O3—C9117.08 (15)
H13A—C13—H13B108.3C10—O4—C11113.38 (18)
O2—C14—H14A109.5C23—O5—H5O107 (3)
O2—C14—H14B109.5O6—C23—O5122.9 (12)
H14A—C14—H14B109.5O6—C23—C24124.8 (10)
O2—C14—H14C109.5O5—C23—C24112.2 (10)
H14A—C14—H14C109.5C24i—C24—C23108.4 (10)
H14B—C14—H14C109.5C24i—C24—H24125.8
O3—C9—C10107.79 (17)C23—C24—H24125.8
O3—C9—H9A110.1C231—O51—H5O113 (2)
C10—C9—H9A110.1O61—C231—O51121.5 (14)
O3—C9—H9B110.1O61—C231—C241120.1 (13)
C10—C9—H9B110.1O51—C231—C241117.6 (12)
H9A—C9—H9B108.5C241i—C241—C231116.8 (11)
O4—C10—C9109.78 (18)C241i—C241—H241121.6
O4—C10—H10A109.7C231—C241—H241121.6
C9—C10—H10A109.7H1W—O1W—H2W108 (3)
O4—C10—H10B109.7H3W—O2W—H4W105 (4)
C9—C10—H10B109.7
N2—C2—C3—C80.3 (3)C17—C18—C19—C21178.8 (2)
N3—C2—C3—C8178.57 (17)C16—C15—C20—C192.0 (3)
N2—C2—C3—C4177.75 (18)N3—C15—C20—C19178.55 (19)
N3—C2—C3—C41.1 (3)C18—C19—C20—C151.3 (3)
C8—C3—C4—C50.7 (3)C21—C19—C20—C15177.28 (19)
C2—C3—C4—C5178.10 (18)N2—C1—N1—C80.2 (3)
C3—C4—C5—O3178.50 (17)C3—C8—N1—C10.3 (3)
C3—C4—C5—C60.7 (3)C7—C8—N1—C1179.06 (17)
C4—C5—C6—O1178.56 (16)N3—C2—N2—C1178.75 (18)
O3—C5—C6—O12.1 (2)C3—C2—N2—C10.1 (3)
C4—C5—C6—C71.6 (3)N1—C1—N2—C20.1 (3)
O3—C5—C6—C7177.77 (16)N2—C2—N3—C1511.0 (3)
O1—C6—C7—C8179.23 (17)C3—C2—N3—C15167.90 (19)
C5—C6—C7—C80.9 (3)C20—C15—N3—C227.6 (3)
C4—C3—C8—N1178.03 (16)C16—C15—N3—C2152.9 (2)
C2—C3—C8—N10.4 (3)C7—C6—O1—C121.3 (3)
C4—C3—C8—C71.4 (3)C5—C6—O1—C12178.78 (16)
C2—C3—C8—C7178.99 (16)C13—C12—O1—C6177.36 (15)
C6—C7—C8—N1178.84 (16)C12—C13—O2—C14175.09 (19)
C6—C7—C8—C30.6 (3)C4—C5—O3—C91.5 (3)
O1—C12—C13—O269.0 (2)C6—C5—O3—C9179.18 (17)
O3—C9—C10—O463.4 (2)C10—C9—O3—C5177.68 (17)
C20—C15—C16—C171.3 (4)C9—C10—O4—C11177.61 (19)
N3—C15—C16—C17179.3 (2)O6—C23—C24—C24i59 (3)
C15—C16—C17—C180.3 (4)O5—C23—C24—C24i118 (2)
C16—C17—C18—C191.0 (4)O61—C231—C241—C241i166 (4)
C17—C18—C19—C200.3 (3)O51—C231—C241—C241i24 (4)
Symmetry code: (i) x, y, z+1.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N3—H3N···O2W0.83 (2)2.22 (2)2.993 (3)155 (2)
O5—H5O···N10.96 (4)1.60 (4)2.560 (3)166 (4)
O1W—H1W···O20.83 (4)2.10 (4)2.884 (3)157 (3)
O1W—H2W···O40.85 (4)2.14 (4)2.956 (3)161 (4)
O2W—H3W···O1Wii0.83 (4)1.99 (4)2.819 (3)175 (3)
O2W—H4W···O6iii0.86 (5)2.03 (6)2.889 (17)176 (5)
C9—H9A···O1Wii0.972.593.436 (4)146
C20—H20···N20.932.332.863 (4)116
C22—H22···O1Wiii0.932.543.444 (4)164
C12—H12A···Cg3iv0.972.763.642 (2)151
Symmetry codes: (ii) x, y+1, z; (iii) x+1, y+1, z+1; (iv) x+1, y+1, z+2.

Experimental details

(I)(II)(III)
Crystal data
Chemical formulaC22H23N3O4·H2OC22H24N3O4+·0.5C2O42C22H23N3O4·0.5C4H4O4·2H2O
Mr411.45438.45487.50
Crystal system, space groupTriclinic, P1Triclinic, P1Triclinic, P1
Temperature (K)294294294
a, b, c (Å)9.0227 (10), 10.4548 (11), 13.2014 (14)7.6285 (8), 10.2252 (10), 14.6525 (14)7.967 (2), 13.248 (4), 13.745 (4)
α, β, γ (°)98.705 (2), 108.738 (2), 111.873 (2)86.076 (2), 84.925 (2), 70.559 (2)108.916 (5), 106.673 (5), 101.909 (5)
V3)1041.05 (19)1072.62 (18)1240.9 (6)
Z222
Radiation typeMo KαMo KαMo Kα
µ (mm1)0.090.100.10
Crystal size (mm)0.19 × 0.13 × 0.090.17 × 0.09 × 0.060.18 × 0.16 × 0.11
Data collection
DiffractometerBruker SMART APEX CCD area-detector
diffractometer
Bruker SMART APEX CCD area-detector
diffractometer
Bruker SMART APEX CCD area-detector
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
10097, 3666, 3169 10367, 3758, 2996 12036, 4364, 3501
Rint0.0170.0320.023
(sin θ/λ)max1)0.5950.5950.595
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.043, 0.120, 1.03 0.067, 0.142, 1.17 0.054, 0.140, 1.08
No. of reflections366637584364
No. of parameters311299379
No. of restraints21056
H-atom treatmentH atoms treated by a mixture of independent and constrained refinementH atoms treated by a mixture of independent and constrained refinementH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.18, 0.280.25, 0.180.27, 0.15

Computer programs: SMART (Bruker, 2001), SAINT (Bruker, 2001), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), DIAMOND (Brandenburg & Putz, 2005).

Hydrogen-bond geometry (Å, º) for (I) top
D—H···AD—HH···AD···AD—H···A
N3—H3N···O1W0.836 (16)2.290 (17)3.1123 (18)167.9 (14)
O1W—H1W···O3i0.80 (2)2.30 (2)3.0485 (18)156 (2)
O1W—H2W···N1ii0.85 (2)2.03 (2)2.8742 (18)173 (2)
C4—H4···O1W0.932.333.248 (2)171
C16—H16···N20.932.272.874 (2)122
C20—H20···O1W0.932.503.323 (2)148
C12—H12B···Cg2iii0.972.763.642 (2)151
Symmetry codes: (i) x+2, y+1, z+2; (ii) x+1, y, z; (iii) x+1, y+1, z+2.
Hydrogen-bond geometry (Å, º) for (II) top
D—H···AD—HH···AD···AD—H···A
N1—H1N···O60.98 (3)1.68 (3)2.633 (3)163 (3)
N3—H3N···O5i0.88 (3)1.94 (3)2.783 (3)160 (2)
C4—H4···O5i0.932.293.087 (3)144
C16—H16···N20.932.292.885 (3)121
C20—H20···O5i0.932.573.225 (3)128
C12—H12B···Cg3ii0.972.773.907 (3)160
Symmetry codes: (i) x, y1, z; (ii) x, y+1, z+1.
Hydrogen-bond geometry (Å, º) for (III) top
D—H···AD—HH···AD···AD—H···A
N3—H3N···O2W0.83 (2)2.22 (2)2.993 (3)155 (2)
O5—H5O···N10.96 (4)1.60 (4)2.560 (3)166 (4)
O1W—H1W···O20.83 (4)2.10 (4)2.884 (3)157 (3)
O1W—H2W···O40.85 (4)2.14 (4)2.956 (3)161 (4)
O2W—H3W···O1Wi0.83 (4)1.99 (4)2.819 (3)175 (3)
O2W—H4W···O6ii0.86 (5)2.03 (6)2.889 (17)176 (5)
C9—H9A···O1Wi0.972.593.436 (4)146
C20—H20···N20.932.332.863 (4)116
C22—H22···O1Wii0.932.543.444 (4)164
C12—H12A···Cg3iii0.972.763.642 (2)151
Symmetry codes: (i) x, y+1, z; (ii) x+1, y+1, z+1; (iii) x+1, y+1, z+2.
Selected geometric parameters (Å ,° ) for I, II and III. top
Parameter(I)(II)(III)45
C23—O5-1.235 (3)1.273 (11)--
C23—O6-1.246 (3)1.214 (11)--
C1—N11.308 (2)1.303 (3)1.303 (3)1.317 (3)1.411
C1—N21.346 (2)1.322 (3)1.334 (3)1.309 (3)1.416
C2—N21.330 (2)1.342 (3)1.327 (3)1.353 (3)1.414
C2—N31.365 (2)1.341 (3)1.351 (3)1.337 (3)1.455
C8—N11.379 (2)1.372 (3)1.373 (2)1.378 (3)1.443
C1—N1—C8115.4 (1)119.7 (2)117.2 (2)120.4 (2)119.6
C2—N2—C1116.8 (1)117.2 (2)117.0 (2)125.4 (2)120.6
C2—N3—C15130.3 (1)130.9 (2)129.2 (2)127.4 (2)134.0
O5—C23—O6-125.2 (2)122.9 (12)--
O5—C23—C23i-116.8 (3)---
O6—C23—C23i-118.0 (3)---
O5—C23—C24#--124.8 (10)--
O6—C23—C24#--112.2 (10)--
C3—C2—N3—C15-179.2 (1)-179.7 (2)167.9 (2)-178.8 (2)-174.9
C2—N3—C15—C16-3.3 (2)8.2 (4)-152.9 (2)-146.2 (2)-138.4
i -x+2, -y+2, -z; # only one disordered component showed; 4 Erlotinib HCl (Selvanayagam et al., 2008); 5. erlotinib-EGFR kinase complex (Stamos et al., 2002)
 

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