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, C
22H
23N
3O
4·H
2O, (I), the erlotinib hemioxalate salt [systematic name: 4-amino-
N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-1-ium hemioxalate], C
22H
24N
3O
4+·0.5C
2O
42-, (II), and the cocrystal erlotinib fumaric acid hemisolvate dihydrate, C
22H
23N
3O
4·0.5C
4H
4O
4·2H
2O, (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
-
stacking.
Supporting information
CCDC references: 765476; 765477; 765478
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).
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.
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).
(I)
N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine
monohydrate
top
Crystal data top
C22H23N3O4·H2O | Z = 2 |
Mr = 411.45 | F(000) = 436 |
Triclinic, P1 | Dx = 1.313 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 9.0227 (10) Å | Cell parameters from 5228 reflections |
b = 10.4548 (11) Å | θ = 2.2–27.9° |
c = 13.2014 (14) Å | µ = 0.09 mm−1 |
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 tube | Rint = 0.017 |
Graphite monochromator | θmax = 25.0°, θmin = 2.2° |
ω scan | h = −10→10 |
10097 measured reflections | k = −12→12 |
3666 independent reflections | l = −15→15 |
Refinement top
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)] = 0.043 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.120 | H 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 parameters | Δρmax = 0.18 e Å−3 |
21 restraints | Δρmin = −0.28 e Å−3 |
Crystal data top
C22H23N3O4·H2O | γ = 111.873 (2)° |
Mr = 411.45 | V = 1041.05 (19) Å3 |
Triclinic, P1 | Z = 2 |
a = 9.0227 (10) Å | Mo Kα radiation |
b = 10.4548 (11) Å | µ = 0.09 mm−1 |
c = 13.2014 (14) Å | T = 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 reflections | Rint = 0.017 |
3666 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.043 | 21 restraints |
wR(F2) = 0.120 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.03 | Δρmax = 0.18 e Å−3 |
3666 reflections | Δρmin = −0.28 e Å−3 |
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 | x | y | z | Uiso*/Ueq | Occ. (<1) |
C1 | 0.75210 (19) | 1.01314 (16) | 1.11192 (14) | 0.0571 (4) | |
H1 | 0.7162 | 1.0809 | 1.1345 | 0.068* | |
C2 | 0.98121 (17) | 0.96540 (14) | 1.11893 (11) | 0.0435 (3) | |
C3 | 0.85915 (16) | 0.82402 (14) | 1.04030 (11) | 0.0413 (3) | |
C4 | 0.90549 (17) | 0.72113 (14) | 0.99468 (11) | 0.0448 (3) | |
H4 | 1.0231 | 0.7435 | 1.0151 | 0.054* | |
C5 | 0.77919 (17) | 0.58952 (14) | 0.92095 (12) | 0.0458 (3) | |
C6 | 0.59847 (17) | 0.55081 (14) | 0.89195 (11) | 0.0450 (3) | |
C7 | 0.55111 (17) | 0.64950 (15) | 0.93433 (11) | 0.0467 (3) | |
H7 | 0.4332 | 0.6250 | 0.9148 | 0.056* | |
C8 | 0.68000 (17) | 0.78811 (14) | 1.00743 (11) | 0.0436 (3) | |
C9 | 0.95945 (19) | 0.52836 (17) | 0.84211 (14) | 0.0584 (4) | |
H9B | 1.0536 | 0.5198 | 0.8974 | 0.070* | |
H9A | 1.0007 | 0.6283 | 0.8422 | 0.070* | |
C10 | 0.9051 (3) | 0.4313 (2) | 0.72896 (16) | 0.0751 (5) | |
H10A | 0.8068 | 0.4366 | 0.6749 | 0.090* | |
H10B | 1.0011 | 0.4622 | 0.7058 | 0.090* | |
C11 | 0.7474 (4) | 0.1821 (3) | 0.6302 (2) | 0.1361 (11) | |
H11A | 0.7222 | 0.0885 | 0.6404 | 0.204* | |
H11B | 0.8031 | 0.1942 | 0.5791 | 0.204* | |
H11C | 0.6402 | 0.1899 | 0.6001 | 0.204* | |
C12 | 0.30426 (18) | 0.37191 (17) | 0.77667 (13) | 0.0591 (4) | |
H12A | 0.2753 | 0.4369 | 0.7381 | 0.071* | |
H12B | 0.2617 | 0.3679 | 0.8355 | 0.071* | |
C13 | 0.2314 (18) | 0.2233 (8) | 0.6960 (8) | 0.073 (3) | 0.554 (7) |
H13A | 0.2869 | 0.1690 | 0.7322 | 0.087* | 0.554 (7) |
H13B | 0.1066 | 0.1718 | 0.6757 | 0.087* | 0.554 (7) |
O2 | 0.2608 (13) | 0.2329 (9) | 0.5980 (8) | 0.077 (2) | 0.554 (7) |
C14 | 0.2189 (9) | 0.1003 (5) | 0.5236 (4) | 0.122 (2) | 0.554 (7) |
H14A | 0.2581 | 0.1185 | 0.4654 | 0.183* | 0.554 (7) |
H14B | 0.0943 | 0.0412 | 0.4907 | 0.183* | 0.554 (7) |
H14C | 0.2757 | 0.0508 | 0.5642 | 0.183* | 0.554 (7) |
C131 | 0.196 (2) | 0.2216 (11) | 0.6928 (11) | 0.069 (3) | 0.446 (7) |
H13C | 0.2303 | 0.1539 | 0.7243 | 0.083* | 0.446 (7) |
H13D | 0.0729 | 0.1908 | 0.6767 | 0.083* | 0.446 (7) |
O21 | 0.2208 (16) | 0.2218 (13) | 0.5925 (11) | 0.085 (3) | 0.446 (7) |
C141 | 0.3550 (8) | 0.1845 (7) | 0.5906 (5) | 0.0836 (18) | 0.446 (7) |
H14D | 0.3673 | 0.1874 | 0.5213 | 0.125* | 0.446 (7) |
H14E | 0.3257 | 0.0886 | 0.5966 | 0.125* | 0.446 (7) |
H14F | 0.4633 | 0.2521 | 0.6526 | 0.125* | 0.446 (7) |
C15 | 1.30051 (17) | 1.13446 (14) | 1.23772 (11) | 0.0449 (3) | |
C16 | 1.2899 (2) | 1.25678 (16) | 1.28597 (12) | 0.0535 (4) | |
H16 | 1.1814 | 1.2566 | 1.2684 | 0.064* | |
C17 | 1.4412 (2) | 1.37874 (17) | 1.36015 (13) | 0.0616 (4) | |
H17 | 1.4330 | 1.4604 | 1.3913 | 0.074* | |
C18 | 1.6036 (2) | 1.38200 (16) | 1.38890 (12) | 0.0602 (4) | |
H18 | 1.7037 | 1.4647 | 1.4394 | 0.072* | |
C19 | 1.61654 (18) | 1.26067 (16) | 1.34183 (12) | 0.0534 (4) | |
C20 | 1.46473 (18) | 1.13763 (15) | 1.26602 (12) | 0.0502 (3) | |
H20 | 1.4734 | 1.0566 | 1.2339 | 0.060* | |
C21 | 1.7847 (2) | 1.26054 (18) | 1.37171 (14) | 0.0641 (4) | |
C22 | 1.9222 (2) | 1.2602 (2) | 1.39920 (19) | 0.0876 (6) | |
H22 | 2.0309 | 1.2600 | 1.4209 | 0.105* | |
N1 | 0.62628 (15) | 0.88598 (13) | 1.04533 (11) | 0.0531 (3) | |
N2 | 0.92649 (15) | 1.05919 (13) | 1.15217 (11) | 0.0535 (3) | |
N3 | 1.15649 (14) | 1.00449 (13) | 1.15992 (10) | 0.0470 (3) | |
H3N | 1.1848 (19) | 0.9423 (17) | 1.1363 (13) | 0.050 (4)* | |
O1 | 0.48834 (12) | 0.41491 (10) | 0.82075 (8) | 0.0555 (3) | |
O3 | 0.81022 (14) | 0.48559 (11) | 0.86847 (11) | 0.0688 (3) | |
O4 | 0.8565 (2) | 0.28741 (14) | 0.73162 (11) | 0.0847 (4) | |
O1W | 1.32150 (16) | 0.80957 (14) | 1.09388 (13) | 0.0706 (4) | |
H1W | 1.316 (3) | 0.745 (3) | 1.120 (2) | 0.085* | |
H2W | 1.405 (3) | 0.828 (2) | 1.0738 (17) | 0.086* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1 | 0.0508 (8) | 0.0498 (8) | 0.0741 (10) | 0.0246 (7) | 0.0308 (8) | 0.0117 (7) |
C2 | 0.0422 (7) | 0.0422 (7) | 0.0479 (7) | 0.0172 (6) | 0.0217 (6) | 0.0163 (6) |
C3 | 0.0397 (7) | 0.0417 (7) | 0.0446 (7) | 0.0171 (6) | 0.0203 (6) | 0.0161 (6) |
C4 | 0.0363 (7) | 0.0438 (7) | 0.0552 (8) | 0.0172 (6) | 0.0211 (6) | 0.0155 (6) |
C5 | 0.0446 (7) | 0.0405 (7) | 0.0550 (8) | 0.0181 (6) | 0.0253 (6) | 0.0138 (6) |
C6 | 0.0418 (7) | 0.0423 (7) | 0.0443 (7) | 0.0124 (6) | 0.0179 (6) | 0.0126 (6) |
C7 | 0.0354 (7) | 0.0512 (8) | 0.0515 (8) | 0.0168 (6) | 0.0184 (6) | 0.0164 (6) |
C8 | 0.0405 (7) | 0.0468 (7) | 0.0479 (7) | 0.0199 (6) | 0.0218 (6) | 0.0171 (6) |
C9 | 0.0506 (8) | 0.0578 (9) | 0.0749 (10) | 0.0279 (7) | 0.0324 (8) | 0.0182 (8) |
C10 | 0.0946 (13) | 0.0755 (11) | 0.0768 (11) | 0.0495 (10) | 0.0453 (10) | 0.0293 (9) |
C11 | 0.178 (3) | 0.0878 (16) | 0.0848 (16) | 0.0264 (17) | 0.0309 (17) | 0.0140 (13) |
C12 | 0.0414 (8) | 0.0585 (9) | 0.0571 (9) | 0.0083 (7) | 0.0145 (7) | 0.0145 (7) |
C13 | 0.045 (5) | 0.059 (3) | 0.072 (4) | −0.003 (2) | 0.006 (2) | 0.018 (3) |
O2 | 0.098 (5) | 0.057 (2) | 0.056 (3) | 0.028 (3) | 0.017 (3) | 0.0123 (19) |
C14 | 0.164 (6) | 0.076 (3) | 0.094 (3) | 0.046 (3) | 0.035 (4) | 0.004 (3) |
C131 | 0.043 (5) | 0.060 (4) | 0.073 (5) | 0.006 (3) | 0.016 (3) | 0.000 (3) |
O21 | 0.074 (4) | 0.098 (6) | 0.055 (3) | 0.041 (3) | 0.002 (2) | 0.000 (3) |
C141 | 0.086 (4) | 0.087 (4) | 0.075 (3) | 0.043 (3) | 0.030 (3) | 0.011 (3) |
C15 | 0.0448 (7) | 0.0408 (7) | 0.0422 (7) | 0.0134 (6) | 0.0161 (6) | 0.0137 (6) |
C16 | 0.0541 (8) | 0.0496 (8) | 0.0492 (8) | 0.0229 (7) | 0.0150 (7) | 0.0110 (6) |
C17 | 0.0694 (10) | 0.0485 (8) | 0.0517 (8) | 0.0248 (8) | 0.0136 (7) | 0.0051 (7) |
C18 | 0.0594 (9) | 0.0478 (8) | 0.0463 (8) | 0.0112 (7) | 0.0088 (7) | 0.0060 (6) |
C19 | 0.0471 (8) | 0.0523 (8) | 0.0463 (8) | 0.0123 (6) | 0.0141 (6) | 0.0147 (6) |
C20 | 0.0469 (8) | 0.0451 (8) | 0.0516 (8) | 0.0157 (6) | 0.0190 (6) | 0.0125 (6) |
C21 | 0.0474 (9) | 0.0580 (9) | 0.0603 (9) | 0.0089 (7) | 0.0128 (7) | 0.0078 (7) |
C22 | 0.0481 (10) | 0.0858 (14) | 0.0990 (15) | 0.0188 (9) | 0.0163 (10) | 0.0106 (11) |
N1 | 0.0445 (6) | 0.0527 (7) | 0.0669 (8) | 0.0243 (6) | 0.0274 (6) | 0.0153 (6) |
N2 | 0.0485 (7) | 0.0458 (7) | 0.0647 (8) | 0.0195 (5) | 0.0266 (6) | 0.0102 (6) |
N3 | 0.0397 (6) | 0.0398 (6) | 0.0548 (7) | 0.0153 (5) | 0.0173 (5) | 0.0086 (5) |
O1 | 0.0443 (5) | 0.0455 (5) | 0.0588 (6) | 0.0104 (4) | 0.0165 (5) | 0.0052 (4) |
O3 | 0.0599 (7) | 0.0431 (6) | 0.1028 (9) | 0.0160 (5) | 0.0491 (6) | 0.0054 (5) |
O4 | 0.1224 (11) | 0.0707 (8) | 0.0702 (8) | 0.0544 (8) | 0.0394 (7) | 0.0174 (6) |
O1W | 0.0510 (7) | 0.0592 (7) | 0.1148 (10) | 0.0278 (6) | 0.0439 (7) | 0.0317 (7) |
Geometric parameters (Å, º) top
C1—N1 | 1.3075 (19) | C12—H12B | 0.9700 |
C1—N2 | 1.3457 (18) | C13—O2 | 1.413 (7) |
C1—H1 | 0.9300 | C13—H13A | 0.9700 |
C2—N2 | 1.3295 (18) | C13—H13B | 0.9700 |
C2—N3 | 1.3647 (17) | O2—C14 | 1.410 (8) |
C2—C3 | 1.4364 (19) | C14—H14A | 0.9600 |
C3—C8 | 1.4107 (18) | C14—H14B | 0.9600 |
C3—C4 | 1.4127 (19) | C14—H14C | 0.9600 |
C4—C5 | 1.3612 (19) | C131—O21 | 1.413 (8) |
C4—H4 | 0.9300 | C131—H13C | 0.9700 |
C5—O3 | 1.3647 (17) | C131—H13D | 0.9700 |
C5—C6 | 1.4246 (18) | O21—C141 | 1.409 (9) |
C6—O1 | 1.3540 (16) | C141—H14D | 0.9600 |
C6—C7 | 1.367 (2) | C141—H14E | 0.9600 |
C7—C8 | 1.408 (2) | C141—H14F | 0.9600 |
C7—H7 | 0.9300 | C15—C16 | 1.391 (2) |
C8—N1 | 1.3794 (18) | C15—C20 | 1.393 (2) |
C9—O3 | 1.4261 (18) | C15—N3 | 1.4122 (17) |
C9—C10 | 1.483 (2) | C16—C17 | 1.384 (2) |
C9—H9B | 0.9700 | C16—H16 | 0.9300 |
C9—H9A | 0.9700 | C17—C18 | 1.376 (2) |
C10—O4 | 1.411 (2) | C17—H17 | 0.9300 |
C10—H10A | 0.9700 | C18—C19 | 1.388 (2) |
C10—H10B | 0.9700 | C18—H18 | 0.9300 |
C11—O4 | 1.368 (3) | C19—C20 | 1.3962 (19) |
C11—H11A | 0.9600 | C19—C21 | 1.440 (2) |
C11—H11B | 0.9600 | C20—H20 | 0.9300 |
C11—H11C | 0.9600 | C21—C22 | 1.177 (2) |
C12—O1 | 1.4293 (18) | C22—H22 | 0.9300 |
C12—C13 | 1.506 (7) | N3—H3N | 0.836 (16) |
C12—C131 | 1.511 (8) | O1W—H1W | 0.80 (2) |
C12—H12A | 0.9700 | O1W—H2W | 0.85 (2) |
| | | |
N1—C1—N2 | 128.76 (13) | C12—C13—H13A | 109.5 |
N1—C1—H1 | 115.6 | O2—C13—H13B | 109.5 |
N2—C1—H1 | 115.6 | C12—C13—H13B | 109.5 |
N2—C2—N3 | 119.37 (12) | H13A—C13—H13B | 108.1 |
N2—C2—C3 | 121.15 (12) | C14—O2—C13 | 115.3 (6) |
N3—C2—C3 | 119.49 (12) | O2—C14—H14A | 109.5 |
C8—C3—C4 | 118.78 (12) | O2—C14—H14B | 109.5 |
C8—C3—C2 | 116.14 (12) | H14A—C14—H14B | 109.5 |
C4—C3—C2 | 125.08 (12) | O2—C14—H14C | 109.5 |
C5—C4—C3 | 120.43 (12) | H14A—C14—H14C | 109.5 |
C5—C4—H4 | 119.8 | H14B—C14—H14C | 109.5 |
C3—C4—H4 | 119.8 | O21—C131—C12 | 109.8 (10) |
C4—C5—O3 | 124.87 (12) | O21—C131—H13C | 109.7 |
C4—C5—C6 | 120.72 (12) | C12—C131—H13C | 109.7 |
O3—C5—C6 | 114.40 (12) | O21—C131—H13D | 109.7 |
O1—C6—C7 | 126.28 (12) | C12—C131—H13D | 109.7 |
O1—C6—C5 | 114.10 (12) | H13C—C131—H13D | 108.2 |
C7—C6—C5 | 119.61 (12) | C141—O21—C131 | 112.9 (11) |
C6—C7—C8 | 120.33 (12) | O21—C141—H14D | 109.5 |
C6—C7—H7 | 119.8 | O21—C141—H14E | 109.5 |
C8—C7—H7 | 119.8 | H14D—C141—H14E | 109.5 |
N1—C8—C7 | 118.42 (12) | O21—C141—H14F | 109.5 |
N1—C8—C3 | 121.56 (12) | H14D—C141—H14F | 109.5 |
C7—C8—C3 | 120.02 (12) | H14E—C141—H14F | 109.5 |
O3—C9—C10 | 107.48 (13) | C16—C15—C20 | 118.82 (13) |
O3—C9—H9B | 110.2 | C16—C15—N3 | 125.21 (13) |
C10—C9—H9B | 110.2 | C20—C15—N3 | 115.97 (12) |
O3—C9—H9A | 110.2 | C17—C16—C15 | 119.80 (14) |
C10—C9—H9A | 110.2 | C17—C16—H16 | 120.1 |
H9B—C9—H9A | 108.5 | C15—C16—H16 | 120.1 |
O4—C10—C9 | 109.79 (15) | C18—C17—C16 | 121.56 (15) |
O4—C10—H10A | 109.7 | C18—C17—H17 | 119.2 |
C9—C10—H10A | 109.7 | C16—C17—H17 | 119.2 |
O4—C10—H10B | 109.7 | C17—C18—C19 | 119.39 (14) |
C9—C10—H10B | 109.7 | C17—C18—H18 | 120.3 |
H10A—C10—H10B | 108.2 | C19—C18—H18 | 120.3 |
O4—C11—H11A | 109.5 | C18—C19—C20 | 119.46 (14) |
O4—C11—H11B | 109.5 | C18—C19—C21 | 120.49 (13) |
H11A—C11—H11B | 109.5 | C20—C19—C21 | 120.05 (14) |
O4—C11—H11C | 109.5 | C15—C20—C19 | 120.97 (14) |
H11A—C11—H11C | 109.5 | C15—C20—H20 | 119.5 |
H11B—C11—H11C | 109.5 | C19—C20—H20 | 119.5 |
O1—C12—C13 | 101.7 (6) | C22—C21—C19 | 178.02 (19) |
O1—C12—C131 | 113.2 (7) | C21—C22—H22 | 180.0 |
O1—C12—H12A | 111.4 | C1—N1—C8 | 115.44 (12) |
C13—C12—H12A | 111.4 | C2—N2—C1 | 116.78 (12) |
C131—C12—H12A | 106.4 | C2—N3—C15 | 130.25 (12) |
O1—C12—H12B | 111.4 | C2—N3—H3N | 116.0 (11) |
C13—C12—H12B | 111.4 | C15—N3—H3N | 113.7 (11) |
C131—C12—H12B | 104.8 | C6—O1—C12 | 118.19 (12) |
H12A—C12—H12B | 109.3 | C5—O3—C9 | 119.26 (11) |
O2—C13—C12 | 110.8 (7) | C11—O4—C10 | 115.55 (17) |
O2—C13—H13A | 109.5 | H1W—O1W—H2W | 106 (2) |
| | | |
N2—C2—C3—C8 | −4.29 (19) | N3—C15—C16—C17 | −179.07 (13) |
N3—C2—C3—C8 | 175.99 (11) | C15—C16—C17—C18 | −0.8 (2) |
N2—C2—C3—C4 | 175.60 (12) | C16—C17—C18—C19 | 0.5 (2) |
N3—C2—C3—C4 | −4.1 (2) | C17—C18—C19—C20 | 0.1 (2) |
C8—C3—C4—C5 | −0.4 (2) | C17—C18—C19—C21 | −179.13 (14) |
C2—C3—C4—C5 | 179.68 (12) | C16—C15—C20—C19 | 0.3 (2) |
C3—C4—C5—O3 | 176.88 (13) | N3—C15—C20—C19 | 179.78 (12) |
C3—C4—C5—C6 | −2.6 (2) | C18—C19—C20—C15 | −0.6 (2) |
C4—C5—C6—O1 | −177.87 (12) | C21—C19—C20—C15 | 178.70 (13) |
O3—C5—C6—O1 | 2.63 (18) | N2—C1—N1—C8 | −3.1 (2) |
C4—C5—C6—C7 | 3.2 (2) | C7—C8—N1—C1 | −179.29 (13) |
O3—C5—C6—C7 | −176.27 (12) | C3—C8—N1—C1 | 0.8 (2) |
O1—C6—C7—C8 | −179.58 (12) | N3—C2—N2—C1 | −177.87 (12) |
C5—C6—C7—C8 | −0.8 (2) | C3—C2—N2—C1 | 2.4 (2) |
C6—C7—C8—N1 | 177.91 (12) | N1—C1—N2—C2 | 1.6 (2) |
C6—C7—C8—C3 | −2.2 (2) | N2—C2—N3—C15 | 1.0 (2) |
C4—C3—C8—N1 | −177.28 (12) | C3—C2—N3—C15 | −179.23 (12) |
C2—C3—C8—N1 | 2.62 (19) | C16—C15—N3—C2 | −3.3 (2) |
C4—C3—C8—C7 | 2.80 (19) | C20—C15—N3—C2 | 177.24 (13) |
C2—C3—C8—C7 | −177.30 (11) | C7—C6—O1—C12 | 5.8 (2) |
O3—C9—C10—O4 | −63.80 (18) | C5—C6—O1—C12 | −172.97 (12) |
O1—C12—C13—O2 | −74.6 (10) | C13—C12—O1—C6 | 175.3 (4) |
C131—C12—C13—O2 | 110 (5) | C131—C12—O1—C6 | 176.4 (6) |
C12—C13—O2—C14 | 171.8 (9) | C4—C5—O3—C9 | −31.4 (2) |
O1—C12—C131—O21 | −70.2 (13) | C6—C5—O3—C9 | 148.11 (13) |
C13—C12—C131—O21 | −65 (4) | C10—C9—O3—C5 | −139.61 (15) |
C12—C131—O21—C141 | 92.9 (14) | C9—C10—O4—C11 | 157.4 (2) |
C20—C15—C16—C17 | 0.3 (2) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H3N···O1W | 0.836 (16) | 2.290 (17) | 3.1123 (18) | 167.9 (14) |
O1W—H1W···O3i | 0.80 (2) | 2.30 (2) | 3.0485 (18) | 156 (2) |
O1W—H2W···N1ii | 0.85 (2) | 2.03 (2) | 2.8742 (18) | 173 (2) |
C4—H4···O1W | 0.93 | 2.33 | 3.248 (2) | 171 |
C16—H16···N2 | 0.93 | 2.27 | 2.874 (2) | 122 |
C20—H20···O1W | 0.93 | 2.50 | 3.323 (2) | 148 |
C12—H12B···Cg2iii | 0.97 | 2.76 | 3.642 (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+·0.5C2O42− | Z = 2 |
Mr = 438.45 | F(000) = 462 |
Triclinic, P1 | Dx = 1.358 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 7.6285 (8) Å | Cell parameters from 2417 reflections |
b = 10.2252 (10) Å | θ = 2.6–24.9° |
c = 14.6525 (14) Å | µ = 0.10 mm−1 |
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 tube | Rint = 0.032 |
Graphite monochromator | θmax = 25.0°, θmin = 2.1° |
ω scan | h = −9→9 |
10367 measured reflections | k = −12→12 |
3758 independent reflections | l = −17→17 |
Refinement top
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)] = 0.067 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.142 | H 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 parameters | Δρmax = 0.25 e Å−3 |
0 restraints | Δρmin = −0.18 e Å−3 |
Crystal data top
C22H24N3O4+·0.5C2O42− | γ = 70.559 (2)° |
Mr = 438.45 | V = 1072.62 (18) Å3 |
Triclinic, P1 | Z = 2 |
a = 7.6285 (8) Å | Mo Kα radiation |
b = 10.2252 (10) Å | µ = 0.10 mm−1 |
c = 14.6525 (14) Å | T = 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 reflections | Rint = 0.032 |
3758 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.067 | 0 restraints |
wR(F2) = 0.142 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.17 | Δρmax = 0.25 e Å−3 |
3758 reflections | Δρmin = −0.18 e Å−3 |
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 | x | y | z | Uiso*/Ueq | |
C1 | 0.6538 (4) | 0.7816 (3) | −0.07682 (19) | 0.0429 (7) | |
H1 | 0.6112 | 0.8643 | −0.1114 | 0.051* | |
C2 | 0.6954 (3) | 0.5508 (2) | −0.05991 (16) | 0.0310 (6) | |
C3 | 0.7603 (3) | 0.5476 (2) | 0.02983 (16) | 0.0309 (6) | |
C4 | 0.8042 (3) | 0.4321 (2) | 0.09165 (17) | 0.0335 (6) | |
H4 | 0.7973 | 0.3484 | 0.0740 | 0.040* | |
C5 | 0.8569 (3) | 0.4401 (2) | 0.17697 (17) | 0.0338 (6) | |
C6 | 0.8739 (3) | 0.5672 (2) | 0.20392 (16) | 0.0330 (6) | |
C7 | 0.8363 (3) | 0.6784 (2) | 0.14350 (17) | 0.0335 (6) | |
H7 | 0.8514 | 0.7602 | 0.1597 | 0.040* | |
C8 | 0.7758 (3) | 0.6712 (2) | 0.05782 (16) | 0.0312 (6) | |
C9 | 0.8641 (4) | 0.2097 (3) | 0.21985 (19) | 0.0493 (7) | |
H9A | 0.9595 | 0.1621 | 0.1740 | 0.059* | |
H9B | 0.7437 | 0.2319 | 0.1946 | 0.059* | |
C10 | 0.8716 (5) | 0.1183 (3) | 0.3037 (2) | 0.0562 (8) | |
H10A | 0.8814 | 0.0259 | 0.2869 | 0.067* | |
H10B | 0.9804 | 0.1114 | 0.3358 | 0.067* | |
C11 | 0.7111 (6) | 0.0936 (4) | 0.4435 (2) | 0.0849 (12) | |
H11A | 0.7200 | 0.0010 | 0.4299 | 0.127* | |
H11B | 0.5982 | 0.1348 | 0.4805 | 0.127* | |
H11C | 0.8161 | 0.0906 | 0.4761 | 0.127* | |
C12 | 0.9330 (4) | 0.6951 (3) | 0.31939 (18) | 0.0433 (7) | |
H12A | 0.8142 | 0.7675 | 0.3117 | 0.052* | |
H12B | 1.0283 | 0.7214 | 0.2820 | 0.052* | |
C13 | 0.9761 (4) | 0.6811 (3) | 0.41766 (19) | 0.0519 (8) | |
H13A | 1.0755 | 0.5944 | 0.4285 | 0.062* | |
H13B | 1.0180 | 0.7566 | 0.4320 | 0.062* | |
C14 | 0.8367 (6) | 0.7054 (4) | 0.5665 (2) | 0.0825 (11) | |
H14A | 0.9538 | 0.6430 | 0.5854 | 0.124* | |
H14B | 0.7368 | 0.6886 | 0.6046 | 0.124* | |
H14C | 0.8324 | 0.7994 | 0.5721 | 0.124* | |
C15 | 0.6377 (3) | 0.4083 (2) | −0.17937 (16) | 0.0323 (6) | |
C16 | 0.5920 (4) | 0.5041 (3) | −0.25221 (18) | 0.0425 (7) | |
H16 | 0.5971 | 0.5930 | −0.2476 | 0.051* | |
C17 | 0.5388 (4) | 0.4675 (3) | −0.33159 (19) | 0.0492 (7) | |
H17 | 0.5054 | 0.5332 | −0.3797 | 0.059* | |
C18 | 0.5342 (4) | 0.3361 (3) | −0.34098 (18) | 0.0465 (7) | |
H18 | 0.4989 | 0.3128 | −0.3951 | 0.056* | |
C19 | 0.5824 (3) | 0.2384 (3) | −0.26931 (18) | 0.0390 (6) | |
C20 | 0.6329 (3) | 0.2752 (3) | −0.18822 (17) | 0.0369 (6) | |
H20 | 0.6636 | 0.2102 | −0.1396 | 0.044* | |
C21 | 0.5722 (4) | 0.1013 (3) | −0.27670 (19) | 0.0480 (7) | |
C22 | 0.5587 (5) | −0.0077 (4) | −0.2842 (2) | 0.0683 (10) | |
H22 | 0.5479 | −0.0946 | −0.2902 | 0.082* | |
N1 | 0.7260 (3) | 0.7866 (2) | −0.00035 (15) | 0.0364 (5) | |
H1N | 0.750 (4) | 0.871 (3) | 0.0137 (19) | 0.064 (9)* | |
N2 | 0.6354 (3) | 0.6701 (2) | −0.10989 (14) | 0.0404 (5) | |
N3 | 0.6931 (3) | 0.4331 (2) | −0.09420 (14) | 0.0329 (5) | |
H3N | 0.745 (3) | 0.356 (3) | −0.0617 (16) | 0.037 (7)* | |
O1 | 0.9253 (2) | 0.56607 (17) | 0.29002 (11) | 0.0401 (4) | |
O2 | 0.8179 (3) | 0.6836 (2) | 0.47428 (13) | 0.0625 (6) | |
O3 | 0.8932 (3) | 0.33528 (17) | 0.24216 (12) | 0.0445 (5) | |
O4 | 0.7096 (3) | 0.1732 (2) | 0.36128 (14) | 0.0647 (6) | |
C23 | 0.9071 (3) | 1.0604 (2) | −0.00605 (17) | 0.0339 (6) | |
O5 | 0.9188 (2) | 1.17606 (16) | −0.02807 (13) | 0.0469 (5) | |
O6 | 0.7588 (3) | 1.03374 (18) | 0.00793 (16) | 0.0617 (6) | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1 | 0.0474 (17) | 0.0312 (14) | 0.0486 (17) | −0.0109 (12) | −0.0094 (14) | 0.0062 (12) |
C2 | 0.0231 (12) | 0.0300 (13) | 0.0387 (14) | −0.0081 (10) | 0.0013 (10) | −0.0003 (11) |
C3 | 0.0230 (13) | 0.0309 (13) | 0.0366 (14) | −0.0072 (10) | 0.0032 (10) | −0.0013 (11) |
C4 | 0.0332 (14) | 0.0274 (13) | 0.0404 (15) | −0.0107 (11) | 0.0003 (11) | −0.0035 (11) |
C5 | 0.0328 (14) | 0.0314 (13) | 0.0363 (15) | −0.0108 (11) | −0.0006 (11) | 0.0037 (11) |
C6 | 0.0263 (13) | 0.0371 (14) | 0.0360 (14) | −0.0115 (11) | 0.0014 (11) | −0.0041 (11) |
C7 | 0.0343 (14) | 0.0282 (13) | 0.0413 (15) | −0.0151 (11) | 0.0007 (11) | −0.0046 (11) |
C8 | 0.0273 (13) | 0.0284 (13) | 0.0371 (14) | −0.0094 (10) | 0.0027 (11) | −0.0014 (11) |
C9 | 0.070 (2) | 0.0324 (15) | 0.0459 (17) | −0.0167 (14) | −0.0061 (15) | −0.0009 (12) |
C10 | 0.070 (2) | 0.0383 (16) | 0.062 (2) | −0.0195 (15) | −0.0141 (17) | 0.0081 (14) |
C11 | 0.117 (3) | 0.086 (3) | 0.058 (2) | −0.045 (3) | −0.005 (2) | 0.010 (2) |
C12 | 0.0415 (16) | 0.0432 (16) | 0.0482 (17) | −0.0168 (13) | −0.0011 (13) | −0.0103 (13) |
C13 | 0.0465 (18) | 0.0565 (19) | 0.0548 (19) | −0.0160 (15) | −0.0109 (15) | −0.0132 (15) |
C14 | 0.126 (3) | 0.082 (3) | 0.045 (2) | −0.042 (2) | −0.003 (2) | −0.0068 (18) |
C15 | 0.0231 (13) | 0.0347 (14) | 0.0367 (14) | −0.0064 (11) | 0.0011 (10) | −0.0053 (11) |
C16 | 0.0465 (16) | 0.0375 (15) | 0.0413 (16) | −0.0109 (13) | −0.0021 (13) | −0.0028 (12) |
C17 | 0.0551 (18) | 0.0502 (18) | 0.0370 (16) | −0.0102 (14) | −0.0058 (13) | 0.0010 (13) |
C18 | 0.0448 (17) | 0.0603 (19) | 0.0342 (15) | −0.0150 (14) | −0.0035 (12) | −0.0098 (14) |
C19 | 0.0323 (14) | 0.0446 (16) | 0.0406 (15) | −0.0123 (12) | −0.0002 (12) | −0.0106 (13) |
C20 | 0.0297 (14) | 0.0365 (14) | 0.0423 (15) | −0.0089 (11) | −0.0009 (11) | −0.0003 (11) |
C21 | 0.0509 (18) | 0.0528 (18) | 0.0434 (16) | −0.0188 (15) | −0.0066 (13) | −0.0102 (14) |
C22 | 0.092 (3) | 0.053 (2) | 0.070 (2) | −0.0324 (19) | −0.0143 (19) | −0.0149 (17) |
N1 | 0.0379 (13) | 0.0296 (12) | 0.0441 (13) | −0.0141 (10) | −0.0060 (10) | 0.0022 (10) |
N2 | 0.0453 (13) | 0.0320 (12) | 0.0436 (13) | −0.0113 (10) | −0.0108 (10) | 0.0027 (10) |
N3 | 0.0324 (12) | 0.0278 (11) | 0.0365 (12) | −0.0069 (9) | −0.0055 (9) | 0.0001 (10) |
O1 | 0.0474 (11) | 0.0379 (10) | 0.0377 (10) | −0.0160 (8) | −0.0088 (8) | −0.0016 (8) |
O2 | 0.0662 (14) | 0.0881 (16) | 0.0384 (12) | −0.0310 (12) | −0.0020 (10) | −0.0104 (11) |
O3 | 0.0583 (12) | 0.0347 (10) | 0.0435 (11) | −0.0183 (9) | −0.0126 (9) | 0.0049 (8) |
O4 | 0.0787 (16) | 0.0508 (13) | 0.0622 (14) | −0.0222 (12) | 0.0049 (12) | 0.0060 (11) |
C23 | 0.0392 (15) | 0.0242 (13) | 0.0403 (15) | −0.0107 (11) | −0.0093 (12) | −0.0057 (11) |
O5 | 0.0462 (11) | 0.0228 (9) | 0.0715 (14) | −0.0099 (8) | −0.0153 (9) | 0.0056 (8) |
O6 | 0.0334 (11) | 0.0325 (11) | 0.1179 (19) | −0.0099 (9) | −0.0049 (11) | 0.0014 (11) |
Geometric parameters (Å, º) top
C1—N1 | 1.303 (3) | C12—C13 | 1.492 (4) |
C1—N2 | 1.322 (3) | C12—H12A | 0.9700 |
C1—H1 | 0.9300 | C12—H12B | 0.9700 |
C2—N3 | 1.341 (3) | C13—O2 | 1.396 (3) |
C2—N2 | 1.342 (3) | C13—H13A | 0.9700 |
C2—C3 | 1.440 (3) | C13—H13B | 0.9700 |
C3—C8 | 1.400 (3) | C14—O2 | 1.412 (3) |
C3—C4 | 1.404 (3) | C14—H14A | 0.9600 |
C4—C5 | 1.362 (3) | C14—H14B | 0.9600 |
C4—H4 | 0.9300 | C14—H14C | 0.9600 |
C5—O3 | 1.359 (3) | C15—C16 | 1.384 (3) |
C5—C6 | 1.433 (3) | C15—C20 | 1.388 (3) |
C6—O1 | 1.352 (3) | C15—N3 | 1.417 (3) |
C6—C7 | 1.360 (3) | C16—C17 | 1.379 (4) |
C7—C8 | 1.390 (3) | C16—H16 | 0.9300 |
C7—H7 | 0.9300 | C17—C18 | 1.373 (4) |
C8—N1 | 1.372 (3) | C17—H17 | 0.9300 |
C9—O3 | 1.437 (3) | C18—C19 | 1.384 (4) |
C9—C10 | 1.486 (4) | C18—H18 | 0.9300 |
C9—H9A | 0.9700 | C19—C20 | 1.393 (3) |
C9—H9B | 0.9700 | C19—C21 | 1.442 (4) |
C10—O4 | 1.404 (4) | C20—H20 | 0.9300 |
C10—H10A | 0.9700 | C21—C22 | 1.166 (4) |
C10—H10B | 0.9700 | C22—H22 | 0.9300 |
C11—O4 | 1.405 (4) | N1—H1N | 0.98 (3) |
C11—H11A | 0.9600 | N3—H3N | 0.88 (3) |
C11—H11B | 0.9600 | C23—O5 | 1.235 (3) |
C11—H11C | 0.9600 | C23—O6 | 1.246 (3) |
C12—O1 | 1.437 (3) | C23—C23i | 1.554 (5) |
| | | |
N1—C1—N2 | 126.1 (2) | H12A—C12—H12B | 108.2 |
N1—C1—H1 | 116.9 | O2—C13—C12 | 110.2 (2) |
N2—C1—H1 | 116.9 | O2—C13—H13A | 109.6 |
N3—C2—N2 | 119.1 (2) | C12—C13—H13A | 109.6 |
N3—C2—C3 | 119.8 (2) | O2—C13—H13B | 109.6 |
N2—C2—C3 | 121.1 (2) | C12—C13—H13B | 109.6 |
C8—C3—C4 | 117.9 (2) | H13A—C13—H13B | 108.1 |
C8—C3—C2 | 116.8 (2) | O2—C14—H14A | 109.5 |
C4—C3—C2 | 125.3 (2) | O2—C14—H14B | 109.5 |
C5—C4—C3 | 121.3 (2) | H14A—C14—H14B | 109.5 |
C5—C4—H4 | 119.3 | O2—C14—H14C | 109.5 |
C3—C4—H4 | 119.3 | H14A—C14—H14C | 109.5 |
O3—C5—C4 | 124.9 (2) | H14B—C14—H14C | 109.5 |
O3—C5—C6 | 115.2 (2) | C16—C15—C20 | 119.2 (2) |
C4—C5—C6 | 119.8 (2) | C16—C15—N3 | 125.3 (2) |
O1—C6—C7 | 125.1 (2) | C20—C15—N3 | 115.4 (2) |
O1—C6—C5 | 115.8 (2) | C17—C16—C15 | 119.9 (3) |
C7—C6—C5 | 119.1 (2) | C17—C16—H16 | 120.1 |
C6—C7—C8 | 120.8 (2) | C15—C16—H16 | 120.1 |
C6—C7—H7 | 119.6 | C18—C17—C16 | 121.2 (3) |
C8—C7—H7 | 119.6 | C18—C17—H17 | 119.4 |
N1—C8—C7 | 120.5 (2) | C16—C17—H17 | 119.4 |
N1—C8—C3 | 118.6 (2) | C17—C18—C19 | 119.6 (2) |
C7—C8—C3 | 120.9 (2) | C17—C18—H18 | 120.2 |
O3—C9—C10 | 109.7 (2) | C19—C18—H18 | 120.2 |
O3—C9—H9A | 109.7 | C18—C19—C20 | 119.6 (2) |
C10—C9—H9A | 109.7 | C18—C19—C21 | 120.4 (2) |
O3—C9—H9B | 109.7 | C20—C19—C21 | 120.0 (2) |
C10—C9—H9B | 109.7 | C15—C20—C19 | 120.5 (2) |
H9A—C9—H9B | 108.2 | C15—C20—H20 | 119.7 |
O4—C10—C9 | 109.6 (2) | C19—C20—H20 | 119.7 |
O4—C10—H10A | 109.8 | C22—C21—C19 | 177.7 (3) |
C9—C10—H10A | 109.8 | C21—C22—H22 | 180.0 |
O4—C10—H10B | 109.8 | C1—N1—C8 | 119.7 (2) |
C9—C10—H10B | 109.8 | C1—N1—H1N | 119.6 (17) |
H10A—C10—H10B | 108.2 | C8—N1—H1N | 120.6 (17) |
O4—C11—H11A | 109.5 | C1—N2—C2 | 117.2 (2) |
O4—C11—H11B | 109.5 | C2—N3—C15 | 130.9 (2) |
H11A—C11—H11B | 109.5 | C2—N3—H3N | 116.0 (16) |
O4—C11—H11C | 109.5 | C15—N3—H3N | 112.8 (16) |
H11A—C11—H11C | 109.5 | C6—O1—C12 | 116.21 (19) |
H11B—C11—H11C | 109.5 | C13—O2—C14 | 112.2 (2) |
O1—C12—C13 | 110.1 (2) | C5—O3—C9 | 116.67 (19) |
O1—C12—H12A | 109.6 | C10—O4—C11 | 112.4 (3) |
C13—C12—H12A | 109.6 | O5—C23—O6 | 125.2 (2) |
O1—C12—H12B | 109.6 | O5—C23—C23i | 116.8 (3) |
C13—C12—H12B | 109.6 | O6—C23—C23i | 118.0 (3) |
| | | |
N3—C2—C3—C8 | 174.1 (2) | C16—C17—C18—C19 | 0.5 (4) |
N2—C2—C3—C8 | −6.4 (3) | C17—C18—C19—C20 | 0.7 (4) |
N3—C2—C3—C4 | −7.6 (3) | C17—C18—C19—C21 | 177.9 (3) |
N2—C2—C3—C4 | 171.9 (2) | C16—C15—C20—C19 | −0.1 (4) |
C8—C3—C4—C5 | 1.3 (3) | N3—C15—C20—C19 | −179.3 (2) |
C2—C3—C4—C5 | −177.0 (2) | C18—C19—C20—C15 | −0.9 (4) |
C3—C4—C5—O3 | 176.8 (2) | C21—C19—C20—C15 | −178.1 (2) |
C3—C4—C5—C6 | −2.0 (4) | N2—C1—N1—C8 | −5.9 (4) |
O3—C5—C6—O1 | 0.6 (3) | C7—C8—N1—C1 | −173.9 (2) |
C4—C5—C6—O1 | 179.5 (2) | C3—C8—N1—C1 | 4.7 (3) |
O3—C5—C6—C7 | −178.7 (2) | N1—C1—N2—C2 | 0.5 (4) |
C4—C5—C6—C7 | 0.2 (3) | N3—C2—N2—C1 | −174.7 (2) |
O1—C6—C7—C8 | −176.9 (2) | C3—C2—N2—C1 | 5.8 (3) |
C5—C6—C7—C8 | 2.3 (3) | N2—C2—N3—C15 | 0.8 (4) |
C6—C7—C8—N1 | 175.5 (2) | C3—C2—N3—C15 | −179.7 (2) |
C6—C7—C8—C3 | −3.1 (3) | C16—C15—N3—C2 | 8.2 (4) |
C4—C3—C8—N1 | −177.4 (2) | C20—C15—N3—C2 | −172.7 (2) |
C2—C3—C8—N1 | 1.1 (3) | C7—C6—O1—C12 | 2.5 (3) |
C4—C3—C8—C7 | 1.2 (3) | C5—C6—O1—C12 | −176.7 (2) |
C2—C3—C8—C7 | 179.7 (2) | C13—C12—O1—C6 | 175.3 (2) |
O3—C9—C10—O4 | 72.7 (3) | C12—C13—O2—C14 | −165.2 (3) |
O1—C12—C13—O2 | −76.5 (3) | C4—C5—O3—C9 | −3.3 (4) |
C20—C15—C16—C17 | 1.3 (4) | C6—C5—O3—C9 | 175.5 (2) |
N3—C15—C16—C17 | −179.6 (2) | C10—C9—O3—C5 | −168.3 (2) |
C15—C16—C17—C18 | −1.5 (4) | C9—C10—O4—C11 | −178.0 (3) |
Symmetry code: (i) −x+2, −y+2, −z. |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1N···O6 | 0.98 (3) | 1.68 (3) | 2.633 (3) | 163 (3) |
N3—H3N···O5ii | 0.88 (3) | 1.94 (3) | 2.783 (3) | 160 (2) |
C4—H4···O5ii | 0.93 | 2.29 | 3.087 (3) | 144 |
C16—H16···N2 | 0.93 | 2.29 | 2.885 (3) | 121 |
C20—H20···O5ii | 0.93 | 2.57 | 3.225 (3) | 128 |
C12—H12B···Cg3iii | 0.97 | 2.77 | 3.907 (3) | 160 |
Symmetry codes: (ii) x, y−1, 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
C22H23N3O4·0.5C4H4O4·2H2O | Z = 2 |
Mr = 487.50 | F(000) = 516 |
Triclinic, P1 | Dx = 1.305 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 7.967 (2) Å | Cell parameters from 3735 reflections |
b = 13.248 (4) Å | θ = 2.7–25.4° |
c = 13.745 (4) Å | µ = 0.10 mm−1 |
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 tube | Rint = 0.023 |
Graphite monochromator | θmax = 25.0°, θmin = 1.7° |
ω scan | h = −9→9 |
12036 measured reflections | k = −15→15 |
4364 independent reflections | l = −16→16 |
Refinement top
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)] = 0.054 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.140 | H 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 parameters | Δρmax = 0.27 e Å−3 |
56 restraints | Δρmin = −0.15 e Å−3 |
Crystal data top
C22H23N3O4·0.5C4H4O4·2H2O | γ = 101.909 (5)° |
Mr = 487.50 | V = 1240.9 (6) Å3 |
Triclinic, P1 | Z = 2 |
a = 7.967 (2) Å | Mo Kα radiation |
b = 13.248 (4) Å | µ = 0.10 mm−1 |
c = 13.745 (4) Å | T = 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 reflections | Rint = 0.023 |
4364 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.054 | 56 restraints |
wR(F2) = 0.140 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.08 | Δρmax = 0.27 e Å−3 |
4364 reflections | Δρmin = −0.15 e Å−3 |
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 | x | y | z | Uiso*/Ueq | Occ. (<1) |
C1 | 0.2800 (3) | 0.44849 (18) | 0.56122 (17) | 0.0551 (5) | |
H1 | 0.3265 | 0.4260 | 0.6179 | 0.066* | |
C2 | 0.3112 (3) | 0.58402 (16) | 0.49437 (15) | 0.0484 (5) | |
C3 | 0.1450 (3) | 0.51298 (16) | 0.39735 (15) | 0.0458 (4) | |
C4 | 0.0631 (3) | 0.54320 (16) | 0.31014 (16) | 0.0496 (5) | |
H4 | 0.1194 | 0.6130 | 0.3120 | 0.060* | |
C5 | −0.0975 (3) | 0.47109 (16) | 0.22336 (16) | 0.0476 (5) | |
C6 | −0.1837 (3) | 0.36345 (16) | 0.21897 (15) | 0.0467 (5) | |
C7 | −0.1073 (3) | 0.33366 (16) | 0.30337 (16) | 0.0492 (5) | |
H7 | −0.1644 | 0.2638 | 0.3012 | 0.059* | |
C8 | 0.0572 (3) | 0.40835 (16) | 0.39349 (15) | 0.0458 (4) | |
C12 | −0.4317 (3) | 0.18723 (17) | 0.11728 (17) | 0.0555 (5) | |
H12A | −0.4733 | 0.1932 | 0.1781 | 0.067* | |
H12B | −0.3468 | 0.1443 | 0.1197 | 0.067* | |
C13 | −0.5933 (3) | 0.12983 (18) | 0.00898 (18) | 0.0593 (5) | |
H13A | −0.6699 | 0.0602 | 0.0048 | 0.071* | |
H13B | −0.6683 | 0.1782 | 0.0024 | 0.071* | |
C14 | −0.6716 (4) | 0.0597 (3) | −0.1849 (2) | 0.0907 (8) | |
H14A | −0.7614 | −0.0065 | −0.1934 | 0.136* | |
H14B | −0.6203 | 0.0397 | −0.2408 | 0.136* | |
H14C | −0.7305 | 0.1145 | −0.1928 | 0.136* | |
C9 | −0.1095 (3) | 0.59846 (18) | 0.13531 (18) | 0.0638 (6) | |
H9A | 0.0111 | 0.6038 | 0.1307 | 0.077* | |
H9B | −0.0932 | 0.6599 | 0.2030 | 0.077* | |
C10 | −0.2369 (3) | 0.6057 (2) | 0.03653 (19) | 0.0663 (6) | |
H10A | −0.3587 | 0.5967 | 0.0399 | 0.080* | |
H10B | −0.1900 | 0.6792 | 0.0364 | 0.080* | |
C11 | −0.3634 (4) | 0.5249 (2) | −0.1587 (2) | 0.0797 (7) | |
H11A | −0.4837 | 0.5224 | −0.1569 | 0.120* | |
H11B | −0.3760 | 0.4613 | −0.2223 | 0.120* | |
H11C | −0.3072 | 0.5936 | −0.1636 | 0.120* | |
C15 | 0.5458 (3) | 0.77727 (17) | 0.59997 (17) | 0.0553 (5) | |
C16 | 0.5613 (3) | 0.88594 (19) | 0.6070 (2) | 0.0713 (6) | |
H16 | 0.4797 | 0.8964 | 0.5504 | 0.086* | |
C17 | 0.6960 (4) | 0.9783 (2) | 0.6969 (2) | 0.0823 (8) | |
H17 | 0.7052 | 1.0506 | 0.7004 | 0.099* | |
C18 | 0.8174 (3) | 0.9643 (2) | 0.7817 (2) | 0.0756 (7) | |
H18 | 0.9070 | 1.0270 | 0.8428 | 0.091* | |
C19 | 0.8060 (3) | 0.85712 (19) | 0.77568 (17) | 0.0593 (6) | |
C20 | 0.6707 (3) | 0.76300 (18) | 0.68390 (16) | 0.0543 (5) | |
H20 | 0.6646 | 0.6906 | 0.6792 | 0.065* | |
C21 | 0.9283 (3) | 0.8393 (2) | 0.86379 (19) | 0.0658 (6) | |
C22 | 1.0233 (4) | 0.8218 (2) | 0.9342 (2) | 0.0820 (8) | |
H22 | 1.0990 | 0.8078 | 0.9903 | 0.098* | |
N1 | 0.1286 (2) | 0.37666 (14) | 0.47802 (13) | 0.0524 (4) | |
N2 | 0.3760 (2) | 0.55060 (14) | 0.57453 (13) | 0.0552 (4) | |
N3 | 0.4026 (3) | 0.68781 (15) | 0.50581 (15) | 0.0588 (5) | |
O1 | −0.34075 (18) | 0.29763 (11) | 0.12739 (11) | 0.0546 (4) | |
O2 | −0.5279 (2) | 0.10611 (14) | −0.07815 (12) | 0.0694 (4) | |
O3 | −0.19004 (18) | 0.49268 (11) | 0.13647 (11) | 0.0571 (4) | |
O4 | −0.2505 (2) | 0.52116 (15) | −0.06071 (13) | 0.0739 (5) | |
H3N | 0.366 (3) | 0.7032 (18) | 0.4514 (18) | 0.058 (6)* | |
O5 | −0.049 (2) | 0.1910 (14) | 0.4751 (14) | 0.094 (3) | 0.55 (2) |
O6 | 0.210 (2) | 0.2101 (11) | 0.6014 (15) | 0.115 (4) | 0.55 (2) |
C23 | 0.0506 (17) | 0.1556 (12) | 0.5382 (14) | 0.080 (3) | 0.55 (2) |
C24 | −0.0502 (17) | 0.0355 (9) | 0.5190 (15) | 0.095 (3) | 0.55 (2) |
H24 | −0.1588 | 0.0124 | 0.5303 | 0.114* | 0.55 (2) |
O51 | −0.003 (3) | 0.1757 (14) | 0.4677 (15) | 0.092 (4) | 0.45 (2) |
O61 | 0.233 (3) | 0.2406 (13) | 0.6283 (14) | 0.105 (3) | 0.45 (2) |
C231 | 0.108 (3) | 0.1610 (13) | 0.5486 (17) | 0.104 (7) | 0.45 (2) |
C241 | 0.057 (4) | 0.0461 (8) | 0.5511 (7) | 0.129 (6) | 0.45 (2) |
H241 | 0.0986 | 0.0365 | 0.6169 | 0.155* | 0.45 (2) |
H5O | 0.033 (5) | 0.256 (3) | 0.476 (3) | 0.137 (13)* | |
O1W | −0.2816 (3) | 0.2842 (2) | −0.09821 (16) | 0.0854 (6) | |
H1W | −0.353 (5) | 0.249 (3) | −0.078 (3) | 0.102* | |
H2W | −0.279 (5) | 0.352 (3) | −0.074 (3) | 0.103* | |
O2W | 0.4029 (4) | 0.77270 (19) | 0.3289 (2) | 0.0933 (7) | |
H3W | 0.361 (5) | 0.753 (3) | 0.260 (3) | 0.112* | |
H4W | 0.518 (7) | 0.779 (4) | 0.347 (4) | 0.119* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1 | 0.0630 (13) | 0.0609 (13) | 0.0453 (11) | 0.0244 (11) | 0.0190 (10) | 0.0256 (10) |
C2 | 0.0539 (11) | 0.0511 (12) | 0.0428 (11) | 0.0214 (9) | 0.0208 (9) | 0.0176 (9) |
C3 | 0.0484 (11) | 0.0500 (11) | 0.0422 (10) | 0.0201 (9) | 0.0209 (9) | 0.0174 (9) |
C4 | 0.0526 (11) | 0.0478 (11) | 0.0495 (11) | 0.0138 (9) | 0.0203 (10) | 0.0222 (9) |
C5 | 0.0471 (11) | 0.0554 (12) | 0.0457 (11) | 0.0196 (9) | 0.0187 (9) | 0.0247 (9) |
C6 | 0.0467 (11) | 0.0503 (11) | 0.0452 (11) | 0.0158 (9) | 0.0211 (9) | 0.0189 (9) |
C7 | 0.0553 (12) | 0.0469 (11) | 0.0497 (11) | 0.0152 (9) | 0.0242 (10) | 0.0225 (9) |
C8 | 0.0519 (11) | 0.0493 (11) | 0.0426 (10) | 0.0217 (9) | 0.0223 (9) | 0.0198 (9) |
C12 | 0.0537 (12) | 0.0560 (12) | 0.0600 (13) | 0.0093 (10) | 0.0269 (10) | 0.0285 (10) |
C13 | 0.0469 (11) | 0.0598 (13) | 0.0688 (14) | 0.0091 (10) | 0.0239 (11) | 0.0271 (11) |
C14 | 0.0785 (18) | 0.104 (2) | 0.0630 (16) | 0.0096 (15) | 0.0093 (14) | 0.0296 (15) |
C9 | 0.0653 (14) | 0.0587 (13) | 0.0627 (13) | 0.0109 (11) | 0.0137 (11) | 0.0345 (11) |
C10 | 0.0708 (15) | 0.0618 (13) | 0.0706 (15) | 0.0224 (11) | 0.0218 (12) | 0.0366 (12) |
C11 | 0.0805 (17) | 0.107 (2) | 0.0630 (15) | 0.0438 (15) | 0.0219 (13) | 0.0458 (15) |
C15 | 0.0542 (12) | 0.0520 (12) | 0.0510 (12) | 0.0145 (10) | 0.0187 (10) | 0.0136 (10) |
C16 | 0.0695 (15) | 0.0585 (14) | 0.0743 (16) | 0.0208 (12) | 0.0169 (13) | 0.0224 (12) |
C17 | 0.0828 (18) | 0.0485 (13) | 0.095 (2) | 0.0167 (13) | 0.0241 (16) | 0.0156 (13) |
C18 | 0.0623 (14) | 0.0619 (15) | 0.0718 (16) | 0.0106 (12) | 0.0183 (13) | 0.0025 (12) |
C19 | 0.0483 (12) | 0.0657 (14) | 0.0522 (12) | 0.0146 (10) | 0.0218 (10) | 0.0105 (11) |
C20 | 0.0514 (11) | 0.0555 (12) | 0.0497 (12) | 0.0161 (10) | 0.0201 (10) | 0.0141 (10) |
C21 | 0.0469 (12) | 0.0807 (16) | 0.0489 (13) | 0.0126 (11) | 0.0174 (11) | 0.0074 (12) |
C22 | 0.0618 (15) | 0.114 (2) | 0.0540 (14) | 0.0308 (15) | 0.0166 (12) | 0.0181 (14) |
N1 | 0.0596 (10) | 0.0552 (10) | 0.0442 (9) | 0.0203 (8) | 0.0181 (8) | 0.0231 (8) |
N2 | 0.0586 (10) | 0.0576 (11) | 0.0462 (9) | 0.0194 (9) | 0.0154 (8) | 0.0215 (8) |
N3 | 0.0646 (12) | 0.0521 (10) | 0.0475 (11) | 0.0115 (9) | 0.0093 (9) | 0.0210 (9) |
O1 | 0.0493 (8) | 0.0536 (8) | 0.0518 (8) | 0.0082 (6) | 0.0115 (7) | 0.0231 (7) |
O2 | 0.0530 (8) | 0.0858 (11) | 0.0544 (9) | 0.0067 (8) | 0.0168 (7) | 0.0240 (8) |
O3 | 0.0521 (8) | 0.0590 (9) | 0.0561 (8) | 0.0101 (7) | 0.0111 (7) | 0.0319 (7) |
O4 | 0.0813 (11) | 0.0913 (12) | 0.0623 (10) | 0.0456 (9) | 0.0227 (8) | 0.0407 (9) |
O5 | 0.079 (5) | 0.082 (5) | 0.113 (5) | 0.011 (3) | 0.021 (3) | 0.056 (4) |
O6 | 0.117 (5) | 0.051 (6) | 0.128 (11) | 0.007 (4) | −0.010 (5) | 0.039 (6) |
C23 | 0.088 (5) | 0.068 (4) | 0.092 (7) | 0.019 (3) | 0.037 (4) | 0.045 (5) |
C24 | 0.077 (5) | 0.071 (5) | 0.143 (9) | 0.019 (4) | 0.043 (5) | 0.052 (6) |
O51 | 0.089 (9) | 0.061 (5) | 0.090 (5) | −0.010 (5) | 0.006 (5) | 0.036 (4) |
O61 | 0.144 (8) | 0.058 (6) | 0.075 (5) | 0.013 (5) | −0.001 (4) | 0.029 (5) |
C231 | 0.130 (13) | 0.060 (5) | 0.086 (7) | −0.001 (7) | 0.009 (8) | 0.035 (5) |
C241 | 0.177 (15) | 0.067 (5) | 0.075 (5) | −0.015 (7) | −0.015 (6) | 0.034 (5) |
O1W | 0.0921 (14) | 0.0888 (15) | 0.0783 (12) | 0.0142 (12) | 0.0415 (11) | 0.0397 (11) |
O2W | 0.1131 (19) | 0.0915 (14) | 0.0732 (14) | 0.0204 (12) | 0.0319 (13) | 0.0427 (12) |
Geometric parameters (Å, º) top
C1—N1 | 1.303 (3) | C11—O4 | 1.411 (3) |
C1—N2 | 1.334 (3) | C11—H11A | 0.9600 |
C1—H1 | 0.9300 | C11—H11B | 0.9600 |
C2—N2 | 1.327 (2) | C11—H11C | 0.9600 |
C2—N3 | 1.351 (3) | C15—C20 | 1.385 (3) |
C2—C3 | 1.441 (3) | C15—C16 | 1.388 (3) |
C3—C8 | 1.394 (3) | C15—N3 | 1.408 (3) |
C3—C4 | 1.412 (3) | C16—C17 | 1.376 (3) |
C4—C5 | 1.361 (3) | C16—H16 | 0.9300 |
C4—H4 | 0.9300 | C17—C18 | 1.376 (3) |
C5—O3 | 1.362 (2) | C17—H17 | 0.9300 |
C5—C6 | 1.423 (3) | C18—C19 | 1.377 (3) |
C6—O1 | 1.358 (2) | C18—H18 | 0.9300 |
C6—C7 | 1.365 (3) | C19—C20 | 1.397 (3) |
C7—C8 | 1.403 (3) | C19—C21 | 1.441 (3) |
C7—H7 | 0.9300 | C20—H20 | 0.9300 |
C8—N1 | 1.373 (2) | C21—C22 | 1.166 (3) |
C12—O1 | 1.434 (2) | C22—H22 | 0.9300 |
C12—C13 | 1.488 (3) | N3—H3N | 0.83 (2) |
C12—H12A | 0.9700 | O5—C23 | 1.273 (11) |
C12—H12B | 0.9700 | O5—H5O | 0.96 (4) |
C13—O2 | 1.409 (3) | O6—C23 | 1.214 (11) |
C13—H13A | 0.9700 | C23—C24 | 1.525 (11) |
C13—H13B | 0.9700 | C24—C24i | 1.424 (13) |
C14—O2 | 1.415 (3) | C24—H24 | 0.9300 |
C14—H14A | 0.9600 | O51—C231 | 1.303 (13) |
C14—H14B | 0.9600 | O51—H5O | 1.01 (4) |
C14—H14C | 0.9600 | O61—C231 | 1.223 (14) |
C9—O3 | 1.423 (2) | C231—C241 | 1.507 (13) |
C9—C10 | 1.489 (3) | C241—C241i | 1.409 (16) |
C9—H9A | 0.9700 | C241—H241 | 0.9300 |
C9—H9B | 0.9700 | O1W—H1W | 0.83 (4) |
C10—O4 | 1.395 (3) | O1W—H2W | 0.85 (4) |
C10—H10A | 0.9700 | O2W—H3W | 0.83 (4) |
C10—H10B | 0.9700 | O2W—H4W | 0.86 (5) |
| | | |
N1—C1—N2 | 127.57 (18) | H10A—C10—H10B | 108.2 |
N1—C1—H1 | 116.2 | O4—C11—H11A | 109.5 |
N2—C1—H1 | 116.2 | O4—C11—H11B | 109.5 |
N2—C2—N3 | 118.73 (18) | H11A—C11—H11B | 109.5 |
N2—C2—C3 | 121.38 (18) | O4—C11—H11C | 109.5 |
N3—C2—C3 | 119.88 (17) | H11A—C11—H11C | 109.5 |
C8—C3—C4 | 118.71 (17) | H11B—C11—H11C | 109.5 |
C8—C3—C2 | 116.10 (17) | C20—C15—C16 | 118.9 (2) |
C4—C3—C2 | 125.14 (18) | C20—C15—N3 | 124.16 (19) |
C5—C4—C3 | 120.65 (18) | C16—C15—N3 | 116.9 (2) |
C5—C4—H4 | 119.7 | C17—C16—C15 | 120.7 (2) |
C3—C4—H4 | 119.7 | C17—C16—H16 | 119.6 |
C4—C5—O3 | 125.43 (18) | C15—C16—H16 | 119.6 |
C4—C5—C6 | 120.17 (17) | C16—C17—C18 | 120.4 (2) |
O3—C5—C6 | 114.40 (16) | C16—C17—H17 | 119.8 |
O1—C6—C7 | 125.14 (17) | C18—C17—H17 | 119.8 |
O1—C6—C5 | 115.04 (16) | C17—C18—C19 | 119.8 (2) |
C7—C6—C5 | 119.82 (17) | C17—C18—H18 | 120.1 |
C6—C7—C8 | 120.08 (17) | C19—C18—H18 | 120.1 |
C6—C7—H7 | 120.0 | C18—C19—C20 | 120.0 (2) |
C8—C7—H7 | 120.0 | C18—C19—C21 | 121.4 (2) |
N1—C8—C3 | 120.83 (17) | C20—C19—C21 | 118.7 (2) |
N1—C8—C7 | 118.63 (17) | C15—C20—C19 | 120.2 (2) |
C3—C8—C7 | 120.54 (17) | C15—C20—H20 | 119.9 |
O1—C12—C13 | 107.70 (16) | C19—C20—H20 | 119.9 |
O1—C12—H12A | 110.2 | C22—C21—C19 | 177.9 (3) |
C13—C12—H12A | 110.2 | C21—C22—H22 | 180.0 |
O1—C12—H12B | 110.2 | C1—N1—C8 | 117.16 (17) |
C13—C12—H12B | 110.2 | C2—N2—C1 | 116.97 (17) |
H12A—C12—H12B | 108.5 | C2—N3—C15 | 129.22 (19) |
O2—C13—C12 | 109.01 (16) | C2—N3—H3N | 116.3 (15) |
O2—C13—H13A | 109.9 | C15—N3—H3N | 114.3 (15) |
C12—C13—H13A | 109.9 | C6—O1—C12 | 117.56 (15) |
O2—C13—H13B | 109.9 | C13—O2—C14 | 113.15 (18) |
C12—C13—H13B | 109.9 | C5—O3—C9 | 117.08 (15) |
H13A—C13—H13B | 108.3 | C10—O4—C11 | 113.38 (18) |
O2—C14—H14A | 109.5 | C23—O5—H5O | 107 (3) |
O2—C14—H14B | 109.5 | O6—C23—O5 | 122.9 (12) |
H14A—C14—H14B | 109.5 | O6—C23—C24 | 124.8 (10) |
O2—C14—H14C | 109.5 | O5—C23—C24 | 112.2 (10) |
H14A—C14—H14C | 109.5 | C24i—C24—C23 | 108.4 (10) |
H14B—C14—H14C | 109.5 | C24i—C24—H24 | 125.8 |
O3—C9—C10 | 107.79 (17) | C23—C24—H24 | 125.8 |
O3—C9—H9A | 110.1 | C231—O51—H5O | 113 (2) |
C10—C9—H9A | 110.1 | O61—C231—O51 | 121.5 (14) |
O3—C9—H9B | 110.1 | O61—C231—C241 | 120.1 (13) |
C10—C9—H9B | 110.1 | O51—C231—C241 | 117.6 (12) |
H9A—C9—H9B | 108.5 | C241i—C241—C231 | 116.8 (11) |
O4—C10—C9 | 109.78 (18) | C241i—C241—H241 | 121.6 |
O4—C10—H10A | 109.7 | C231—C241—H241 | 121.6 |
C9—C10—H10A | 109.7 | H1W—O1W—H2W | 108 (3) |
O4—C10—H10B | 109.7 | H3W—O2W—H4W | 105 (4) |
C9—C10—H10B | 109.7 | | |
| | | |
N2—C2—C3—C8 | 0.3 (3) | C17—C18—C19—C21 | −178.8 (2) |
N3—C2—C3—C8 | −178.57 (17) | C16—C15—C20—C19 | 2.0 (3) |
N2—C2—C3—C4 | 177.75 (18) | N3—C15—C20—C19 | −178.55 (19) |
N3—C2—C3—C4 | −1.1 (3) | C18—C19—C20—C15 | −1.3 (3) |
C8—C3—C4—C5 | −0.7 (3) | C21—C19—C20—C15 | 177.28 (19) |
C2—C3—C4—C5 | −178.10 (18) | N2—C1—N1—C8 | −0.2 (3) |
C3—C4—C5—O3 | 178.50 (17) | C3—C8—N1—C1 | 0.3 (3) |
C3—C4—C5—C6 | −0.7 (3) | C7—C8—N1—C1 | −179.06 (17) |
C4—C5—C6—O1 | −178.56 (16) | N3—C2—N2—C1 | 178.75 (18) |
O3—C5—C6—O1 | 2.1 (2) | C3—C2—N2—C1 | −0.1 (3) |
C4—C5—C6—C7 | 1.6 (3) | N1—C1—N2—C2 | 0.1 (3) |
O3—C5—C6—C7 | −177.77 (16) | N2—C2—N3—C15 | −11.0 (3) |
O1—C6—C7—C8 | 179.23 (17) | C3—C2—N3—C15 | 167.90 (19) |
C5—C6—C7—C8 | −0.9 (3) | C20—C15—N3—C2 | 27.6 (3) |
C4—C3—C8—N1 | −178.03 (16) | C16—C15—N3—C2 | −152.9 (2) |
C2—C3—C8—N1 | −0.4 (3) | C7—C6—O1—C12 | −1.3 (3) |
C4—C3—C8—C7 | 1.4 (3) | C5—C6—O1—C12 | 178.78 (16) |
C2—C3—C8—C7 | 178.99 (16) | C13—C12—O1—C6 | −177.36 (15) |
C6—C7—C8—N1 | 178.84 (16) | C12—C13—O2—C14 | −175.09 (19) |
C6—C7—C8—C3 | −0.6 (3) | C4—C5—O3—C9 | 1.5 (3) |
O1—C12—C13—O2 | 69.0 (2) | C6—C5—O3—C9 | −179.18 (17) |
O3—C9—C10—O4 | −63.4 (2) | C10—C9—O3—C5 | −177.68 (17) |
C20—C15—C16—C17 | −1.3 (4) | C9—C10—O4—C11 | −177.61 (19) |
N3—C15—C16—C17 | 179.3 (2) | O6—C23—C24—C24i | −59 (3) |
C15—C16—C17—C18 | −0.3 (4) | O5—C23—C24—C24i | 118 (2) |
C16—C17—C18—C19 | 1.0 (4) | O61—C231—C241—C241i | −166 (4) |
C17—C18—C19—C20 | −0.3 (3) | O51—C231—C241—C241i | 24 (4) |
Symmetry code: (i) −x, −y, −z+1. |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H3N···O2W | 0.83 (2) | 2.22 (2) | 2.993 (3) | 155 (2) |
O5—H5O···N1 | 0.96 (4) | 1.60 (4) | 2.560 (3) | 166 (4) |
O1W—H1W···O2 | 0.83 (4) | 2.10 (4) | 2.884 (3) | 157 (3) |
O1W—H2W···O4 | 0.85 (4) | 2.14 (4) | 2.956 (3) | 161 (4) |
O2W—H3W···O1Wii | 0.83 (4) | 1.99 (4) | 2.819 (3) | 175 (3) |
O2W—H4W···O6iii | 0.86 (5) | 2.03 (6) | 2.889 (17) | 176 (5) |
C9—H9A···O1Wii | 0.97 | 2.59 | 3.436 (4) | 146 |
C20—H20···N2 | 0.93 | 2.33 | 2.863 (4) | 116 |
C22—H22···O1Wiii | 0.93 | 2.54 | 3.444 (4) | 164 |
C12—H12A···Cg3iv | 0.97 | 2.76 | 3.642 (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 formula | C22H23N3O4·H2O | C22H24N3O4+·0.5C2O42− | C22H23N3O4·0.5C4H4O4·2H2O |
Mr | 411.45 | 438.45 | 487.50 |
Crystal system, space group | Triclinic, P1 | Triclinic, P1 | Triclinic, P1 |
Temperature (K) | 294 | 294 | 294 |
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) |
V (Å3) | 1041.05 (19) | 1072.62 (18) | 1240.9 (6) |
Z | 2 | 2 | 2 |
Radiation type | Mo Kα | Mo Kα | Mo Kα |
µ (mm−1) | 0.09 | 0.10 | 0.10 |
Crystal size (mm) | 0.19 × 0.13 × 0.09 | 0.17 × 0.09 × 0.06 | 0.18 × 0.16 × 0.11 |
|
Data collection |
Diffractometer | Bruker 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 |
Rint | 0.017 | 0.032 | 0.023 |
(sin θ/λ)max (Å−1) | 0.595 | 0.595 | 0.595 |
|
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 reflections | 3666 | 3758 | 4364 |
No. of parameters | 311 | 299 | 379 |
No. of restraints | 21 | 0 | 56 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement | H atoms treated by a mixture of independent and constrained refinement | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.18, −0.28 | 0.25, −0.18 | 0.27, −0.15 |
Hydrogen-bond geometry (Å, º) for (I) top
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H3N···O1W | 0.836 (16) | 2.290 (17) | 3.1123 (18) | 167.9 (14) |
O1W—H1W···O3i | 0.80 (2) | 2.30 (2) | 3.0485 (18) | 156 (2) |
O1W—H2W···N1ii | 0.85 (2) | 2.03 (2) | 2.8742 (18) | 173 (2) |
C4—H4···O1W | 0.93 | 2.33 | 3.248 (2) | 171 |
C16—H16···N2 | 0.93 | 2.27 | 2.874 (2) | 122 |
C20—H20···O1W | 0.93 | 2.50 | 3.323 (2) | 148 |
C12—H12B···Cg2iii | 0.97 | 2.76 | 3.642 (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···A | D—H | H···A | D···A | D—H···A |
N1—H1N···O6 | 0.98 (3) | 1.68 (3) | 2.633 (3) | 163 (3) |
N3—H3N···O5i | 0.88 (3) | 1.94 (3) | 2.783 (3) | 160 (2) |
C4—H4···O5i | 0.93 | 2.29 | 3.087 (3) | 144 |
C16—H16···N2 | 0.93 | 2.29 | 2.885 (3) | 121 |
C20—H20···O5i | 0.93 | 2.57 | 3.225 (3) | 128 |
C12—H12B···Cg3ii | 0.97 | 2.77 | 3.907 (3) | 160 |
Symmetry codes: (i) x, y−1, z; (ii) −x, −y+1, −z+1. |
Hydrogen-bond geometry (Å, º) for (III) top
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H3N···O2W | 0.83 (2) | 2.22 (2) | 2.993 (3) | 155 (2) |
O5—H5O···N1 | 0.96 (4) | 1.60 (4) | 2.560 (3) | 166 (4) |
O1W—H1W···O2 | 0.83 (4) | 2.10 (4) | 2.884 (3) | 157 (3) |
O1W—H2W···O4 | 0.85 (4) | 2.14 (4) | 2.956 (3) | 161 (4) |
O2W—H3W···O1Wi | 0.83 (4) | 1.99 (4) | 2.819 (3) | 175 (3) |
O2W—H4W···O6ii | 0.86 (5) | 2.03 (6) | 2.889 (17) | 176 (5) |
C9—H9A···O1Wi | 0.97 | 2.59 | 3.436 (4) | 146 |
C20—H20···N2 | 0.93 | 2.33 | 2.863 (4) | 116 |
C22—H22···O1Wii | 0.93 | 2.54 | 3.444 (4) | 164 |
C12—H12A···Cg3iii | 0.97 | 2.76 | 3.642 (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. topParameter | (I) | (II) | (III) | 4 | 5 |
C23—O5 | - | 1.235 (3) | 1.273 (11) | - | - |
C23—O6 | - | 1.246 (3) | 1.214 (11) | - | - |
C1—N1 | 1.308 (2) | 1.303 (3) | 1.303 (3) | 1.317 (3) | 1.411 |
C1—N2 | 1.346 (2) | 1.322 (3) | 1.334 (3) | 1.309 (3) | 1.416 |
C2—N2 | 1.330 (2) | 1.342 (3) | 1.327 (3) | 1.353 (3) | 1.414 |
C2—N3 | 1.365 (2) | 1.341 (3) | 1.351 (3) | 1.337 (3) | 1.455 |
C8—N1 | 1.379 (2) | 1.372 (3) | 1.373 (2) | 1.378 (3) | 1.443 |
C1—N1—C8 | 115.4 (1) | 119.7 (2) | 117.2 (2) | 120.4 (2) | 119.6 |
C2—N2—C1 | 116.8 (1) | 117.2 (2) | 117.0 (2) | 125.4 (2) | 120.6 |
C2—N3—C15 | 130.3 (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) |
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 C═O 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 π–π 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.