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Erlotinib is a BCS (biopharmaceutical classification system) class II drug used for the treatment of non-small cell lung cancer. There is an urgent need to obtain new solid forms of higher solubility to improve the bioavailability of the API (active pharmaceutical ingredient). In this context, cocrystals with urea, succinic acid, and glutaric acid and salts with maleic acid, adipic acid, and saccharin were prepared via wet granulation and solution crystallizations. Crystal structures of the free base (Z′ = 2), cocrystals of erlotinib–urea (1:1), erlotinib–succinic acid monohydrate (1:1:1), erlotinib–glutaric acid monohydrate (1:1:1) and salts of erlotinib–adipic acid adipate (1:0.5:0.5) are determined and their hydrogen-bonding patterns are analyzed. Self recognition via the (amine) N—H...N (pyridine) hydrogen bond between the API molecules is replaced by several heterosynthons such as acid–pyridine, amide–pyridine and carboxylate–pyridinium in the new binary systems. Auxiliary interactions play an important role in determining the conformation of the API in the crystal. FT–IR spectroscopy is used to distinguish between the salts and cocrystals in the new multi-component systems. The new solid forms are characterized by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) to confirm their unique phase identity.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S2052520616003607/zb5050sup1.cif
Contains datablocks ETB, Erlotinib-Adipic-adipate, Erlotinib-glutaric-hydrate, Erlotinib-succinic-hydrate, Erlotinib-urea

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S2052520616003607/zb5050ETBsup2.hkl
Contains datablock ETB

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S2052520616003607/zb5050Erlotinib-Adipic-adipatesup3.hkl
Contains datablock Erlotinib-Adipic-adipate

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S2052520616003607/zb5050Erlotinib-glutaric-hydratesup4.hkl
Contains datablock Erlotinib-glutaric-hydrate

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S2052520616003607/zb5050Erlotinib-succinic-hydratesup5.hkl
Contains datablock Erlotinib-succinic-hydrate

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S2052520616003607/zb5050Erlotinib-ureasup6.hkl
Contains datablock Erlotinib-urea

pdf

Portable Document Format (PDF) file https://doi.org/10.1107/S2052520616003607/zb5050sup7.pdf
Neutron-normalized hydrogen-bonding parameters, melting points, FT-IR frequencies, DSC, FT-IR and PXRD of erlotinib cocrystals and salts

CCDC references: 1051785; 1051786; 1051787; 1051788; 1430934

Computing details top

For all compounds, program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997).

(ETB) top
Crystal data top
C22H23N3O4F(000) = 832
Mr = 393.43Dx = 1.307 Mg m3
Monoclinic, PcMo Kα radiation, λ = 0.71073 Å
a = 13.966 (5) ÅCell parameters from 5484 reflections
b = 12.991 (4) Åθ = 2.4–27.5°
c = 11.225 (4) ŵ = 0.09 mm1
β = 100.931 (16)°T = 150 K
V = 1999.6 (11) Å3Plate, colorless
Z = 40.40 × 0.10 × 0.08 mm
Data collection top
XtaLABmini
diffractometer
7841 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.153
Graphite monochromatorθmax = 27.8°, θmin = 1.5°
Absorption correction: multi-scan
SADABS
h = 1818
Tmin = 0.769, Tmax = 1.000k = 1616
20777 measured reflectionsl = 1414
9220 independent reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.090H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.235 w = 1/[σ2(Fo2) + (0.1306P)2 + 0.1558P]
where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max < 0.001
9220 reflectionsΔρmax = 0.45 e Å3
535 parametersΔρmin = 0.55 e Å3
2 restraintsAbsolute structure: Flack H D (1983), Acta Cryst. A39, 876-881
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: 2.0 (12)
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O50.62474 (19)0.3201 (2)0.6791 (2)0.0262 (5)
O80.69754 (19)0.6536 (2)0.7621 (2)0.0293 (6)
O70.56848 (19)0.50326 (19)0.6648 (2)0.0266 (6)
N50.2473 (2)0.3410 (2)0.2628 (3)0.0244 (6)
C340.3812 (2)0.3932 (3)0.4202 (3)0.0194 (6)
C370.5435 (3)0.3351 (3)0.5939 (3)0.0210 (6)
N60.3532 (2)0.2134 (2)0.3700 (3)0.0243 (6)
N40.2699 (2)0.5134 (2)0.3019 (3)0.0218 (6)
C390.6614 (3)0.2178 (3)0.7023 (4)0.0270 (7)
H39A0.68310.19030.63160.032*
H39B0.61110.17300.72220.032*
C350.4352 (2)0.4686 (3)0.4956 (3)0.0215 (7)
H350.41740.53760.48630.026*
C310.2985 (2)0.4159 (3)0.3273 (3)0.0199 (6)
C290.1873 (3)0.5413 (3)0.2102 (3)0.0218 (6)
C330.4071 (2)0.2891 (3)0.4377 (3)0.0209 (7)
C360.5133 (2)0.4405 (2)0.5816 (3)0.0198 (6)
C260.0289 (3)0.6031 (3)0.0362 (3)0.0279 (7)
H260.02390.62320.02280.033*
C240.0842 (3)0.5428 (3)0.1645 (4)0.0297 (8)
C280.2024 (3)0.5876 (3)0.1050 (3)0.0252 (7)
H280.26550.59820.09220.030*
C320.2783 (3)0.2443 (3)0.2905 (3)0.0277 (7)
H320.24120.19250.24690.033*
C250.0135 (3)0.5579 (3)0.1422 (3)0.0250 (7)
C380.4898 (3)0.2612 (3)0.5244 (3)0.0214 (7)
H380.50800.19240.53430.026*
O60.7178 (3)0.2450 (3)0.9204 (3)0.0459 (8)
C270.1228 (3)0.6184 (3)0.0177 (3)0.0283 (8)
H270.13300.64950.05340.034*
C430.6025 (3)0.6500 (3)0.7856 (3)0.0246 (7)
H43A0.58090.71860.80220.030*
H43B0.60060.60690.85570.030*
C420.5374 (3)0.6062 (3)0.6753 (3)0.0250 (7)
H42A0.46980.60790.68480.030*
H42B0.54350.64550.60360.030*
C300.0936 (3)0.5265 (3)0.2300 (3)0.0241 (7)
H300.08360.49580.30150.029*
C230.1640 (3)0.5287 (4)0.1812 (4)0.0350 (9)
H230.22690.51760.19440.042*
C440.7683 (4)0.6819 (4)0.8663 (4)0.0449 (11)
H44A0.77820.62550.92260.067*
H44B0.74540.74080.90440.067*
H44C0.82870.69850.84200.067*
C410.7100 (4)0.3506 (4)0.9494 (4)0.0491 (12)
H41A0.65160.37870.90140.074*
H41B0.76560.38720.93250.074*
H41C0.70750.35731.03390.074*
C400.7466 (3)0.2255 (3)0.8091 (4)0.0309 (8)
H40A0.78310.16160.81550.037*
H40B0.78980.28020.79320.037*
O10.0848 (2)0.1824 (2)1.0454 (3)0.0284 (6)
O30.1411 (2)0.0018 (2)1.0589 (3)0.0292 (6)
N30.3584 (2)0.2876 (2)0.8724 (3)0.0246 (6)
N10.4377 (2)0.0133 (2)0.8381 (3)0.0239 (6)
C150.1666 (3)0.1660 (3)1.0016 (3)0.0218 (7)
C110.3039 (3)0.2114 (3)0.9118 (3)0.0200 (6)
C140.1959 (3)0.0605 (3)1.0037 (3)0.0229 (7)
N20.4627 (2)0.1591 (2)0.8153 (3)0.0261 (6)
C160.2208 (3)0.2398 (3)0.9588 (3)0.0245 (7)
H160.20300.30870.96050.029*
C50.5219 (3)0.0400 (3)0.7896 (3)0.0220 (7)
C130.2738 (2)0.0317 (3)0.9550 (3)0.0221 (7)
H130.29100.03740.95360.026*
O40.0155 (2)0.1522 (2)1.1064 (3)0.0338 (6)
C170.0490 (3)0.2862 (3)1.0470 (4)0.0276 (8)
H17A0.03090.31260.96500.033*
H17B0.09880.33061.09230.033*
C100.4335 (3)0.2559 (3)0.8285 (3)0.0266 (7)
H100.47160.30730.80330.032*
C40.6145 (3)0.0211 (3)0.8566 (3)0.0259 (7)
H40.62180.01100.93190.031*
C120.3286 (2)0.1071 (3)0.9065 (3)0.0210 (7)
C90.4111 (2)0.0848 (3)0.8530 (3)0.0197 (6)
C200.1741 (3)0.1054 (3)1.0834 (3)0.0256 (7)
H20A0.24250.10651.12130.031*
H20B0.16550.14511.00890.031*
O20.0140 (3)0.2689 (3)1.2335 (3)0.0502 (9)
C30.6969 (3)0.0503 (3)0.8109 (3)0.0267 (7)
C80.6848 (3)0.0988 (3)0.6987 (4)0.0303 (8)
H80.73900.11790.66690.036*
C20.7926 (3)0.0314 (3)0.8824 (4)0.0357 (9)
C210.1129 (3)0.1483 (3)1.1671 (3)0.0274 (7)
H21A0.13540.21681.19290.033*
H21B0.11840.10501.23850.033*
C60.5100 (3)0.0898 (3)0.6790 (3)0.0286 (7)
H60.44780.10360.63530.034*
C180.0386 (3)0.2825 (3)1.1070 (4)0.0359 (9)
H18A0.07510.34601.08990.043*
H18B0.08060.22631.07220.043*
C220.0489 (4)0.1753 (4)1.1833 (5)0.0466 (11)
H22A0.04630.12191.24280.070*
H22B0.03080.23971.22320.070*
H22C0.11390.18031.13680.070*
C70.5915 (3)0.1187 (3)0.6340 (3)0.0310 (8)
H70.58380.15190.55940.037*
C10.8711 (3)0.0140 (4)0.9415 (4)0.0428 (11)
H10.93240.00030.98770.051*
C190.0046 (5)0.1672 (5)1.2737 (5)0.0583 (14)
H19A0.05710.14041.26240.087*
H19B0.05630.12661.22820.087*
H19C0.00810.16471.35830.087*
H1N0.414 (2)0.072 (3)0.862 (3)0.000 (7)*
H4N0.301 (4)0.555 (4)0.324 (5)0.033 (14)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O50.0238 (13)0.0197 (12)0.0300 (12)0.0045 (10)0.0079 (10)0.0034 (10)
O80.0194 (13)0.0313 (14)0.0339 (13)0.0002 (11)0.0033 (10)0.0057 (11)
O70.0233 (13)0.0170 (12)0.0326 (13)0.0032 (9)0.0120 (10)0.0050 (9)
N50.0221 (14)0.0193 (14)0.0278 (14)0.0013 (12)0.0057 (11)0.0064 (11)
C340.0169 (15)0.0155 (15)0.0245 (15)0.0018 (12)0.0003 (12)0.0019 (12)
C370.0198 (15)0.0179 (15)0.0232 (15)0.0001 (13)0.0009 (12)0.0019 (12)
N60.0261 (15)0.0158 (13)0.0284 (14)0.0011 (12)0.0017 (12)0.0036 (11)
N40.0149 (14)0.0159 (14)0.0302 (14)0.0023 (12)0.0068 (11)0.0011 (12)
C390.0219 (18)0.0197 (17)0.0375 (19)0.0035 (13)0.0008 (14)0.0065 (14)
C350.0201 (16)0.0141 (15)0.0282 (16)0.0007 (12)0.0011 (13)0.0003 (12)
C310.0196 (15)0.0165 (16)0.0218 (14)0.0012 (12)0.0003 (12)0.0012 (12)
C290.0202 (15)0.0170 (15)0.0254 (15)0.0026 (13)0.0023 (12)0.0024 (12)
C330.0196 (16)0.0186 (16)0.0236 (15)0.0013 (12)0.0016 (13)0.0008 (12)
C360.0198 (15)0.0137 (15)0.0229 (15)0.0008 (12)0.0036 (12)0.0008 (12)
C260.0260 (18)0.0255 (18)0.0274 (17)0.0030 (14)0.0073 (14)0.0011 (14)
C240.0227 (17)0.0254 (19)0.0384 (19)0.0044 (14)0.0012 (14)0.0008 (15)
C280.0236 (16)0.0224 (17)0.0294 (17)0.0020 (14)0.0043 (14)0.0016 (14)
C320.0287 (18)0.0172 (16)0.0329 (18)0.0009 (14)0.0051 (14)0.0021 (14)
C250.0214 (17)0.0203 (16)0.0312 (17)0.0007 (13)0.0002 (13)0.0030 (13)
C380.0227 (16)0.0148 (15)0.0254 (15)0.0030 (13)0.0013 (13)0.0009 (12)
O60.0447 (19)0.058 (2)0.0309 (14)0.0141 (17)0.0034 (13)0.0107 (14)
C270.033 (2)0.0275 (19)0.0235 (16)0.0025 (15)0.0033 (14)0.0030 (13)
C430.0277 (18)0.0204 (16)0.0245 (16)0.0014 (14)0.0018 (13)0.0058 (13)
C420.0214 (17)0.0190 (17)0.0318 (17)0.0035 (13)0.0025 (13)0.0040 (13)
C300.0227 (17)0.0209 (16)0.0274 (16)0.0023 (13)0.0013 (13)0.0018 (13)
C230.0195 (18)0.038 (2)0.046 (2)0.0032 (16)0.0029 (16)0.0035 (18)
C440.040 (3)0.041 (3)0.044 (2)0.004 (2)0.016 (2)0.001 (2)
C410.043 (3)0.064 (3)0.038 (2)0.006 (2)0.0008 (19)0.007 (2)
C400.0206 (17)0.033 (2)0.0359 (19)0.0002 (15)0.0025 (15)0.0087 (16)
O10.0253 (13)0.0189 (13)0.0427 (14)0.0036 (10)0.0111 (11)0.0014 (11)
O30.0260 (14)0.0174 (12)0.0471 (16)0.0034 (10)0.0148 (12)0.0084 (11)
N30.0247 (15)0.0152 (13)0.0330 (15)0.0016 (11)0.0032 (12)0.0030 (11)
N10.0197 (15)0.0166 (14)0.0364 (16)0.0014 (11)0.0083 (12)0.0026 (12)
C150.0194 (16)0.0225 (17)0.0227 (15)0.0037 (13)0.0018 (12)0.0011 (13)
C110.0217 (16)0.0143 (15)0.0211 (14)0.0001 (12)0.0033 (12)0.0012 (12)
C140.0223 (16)0.0187 (16)0.0263 (16)0.0000 (13)0.0010 (12)0.0044 (13)
N20.0251 (15)0.0182 (14)0.0352 (16)0.0000 (12)0.0065 (12)0.0016 (12)
C160.0306 (19)0.0168 (16)0.0246 (16)0.0034 (14)0.0015 (14)0.0007 (12)
C50.0194 (16)0.0133 (15)0.0339 (17)0.0017 (12)0.0061 (13)0.0029 (13)
C130.0188 (16)0.0160 (16)0.0294 (16)0.0008 (12)0.0007 (13)0.0001 (12)
O40.0253 (14)0.0355 (16)0.0401 (15)0.0012 (11)0.0050 (11)0.0103 (12)
C170.0207 (17)0.0213 (17)0.0390 (19)0.0047 (14)0.0016 (15)0.0063 (14)
C100.0269 (18)0.0171 (16)0.0370 (18)0.0020 (14)0.0089 (14)0.0040 (14)
C40.0254 (18)0.0202 (16)0.0310 (17)0.0034 (14)0.0031 (14)0.0033 (13)
C120.0183 (15)0.0181 (16)0.0244 (15)0.0020 (12)0.0017 (12)0.0011 (12)
C90.0188 (15)0.0166 (15)0.0216 (14)0.0009 (12)0.0017 (11)0.0002 (11)
C200.0242 (17)0.0164 (16)0.0351 (18)0.0046 (13)0.0030 (14)0.0050 (13)
O20.051 (2)0.056 (2)0.0467 (18)0.0124 (17)0.0175 (16)0.0181 (16)
C30.0213 (17)0.0206 (17)0.0371 (19)0.0037 (13)0.0031 (14)0.0031 (14)
C80.0318 (19)0.0281 (19)0.0336 (19)0.0062 (16)0.0127 (15)0.0034 (15)
C20.0243 (19)0.031 (2)0.052 (2)0.0107 (16)0.0061 (17)0.0058 (18)
C210.0288 (19)0.0245 (18)0.0265 (16)0.0008 (15)0.0010 (14)0.0026 (14)
C60.0276 (18)0.0222 (17)0.0331 (18)0.0006 (14)0.0018 (14)0.0023 (14)
C180.0192 (17)0.032 (2)0.056 (2)0.0023 (15)0.0047 (17)0.0108 (18)
C220.044 (3)0.039 (3)0.061 (3)0.005 (2)0.022 (2)0.009 (2)
C70.044 (2)0.0222 (18)0.0261 (17)0.0035 (16)0.0042 (16)0.0004 (14)
C10.028 (2)0.040 (2)0.055 (3)0.0096 (18)0.0055 (19)0.003 (2)
C190.054 (3)0.073 (4)0.050 (3)0.006 (3)0.013 (2)0.008 (3)
Geometric parameters (Å, º) top
O5—C371.352 (4)O1—C151.343 (4)
O5—C391.431 (4)O1—C171.440 (4)
O8—C431.402 (4)O3—C141.342 (4)
O8—C441.428 (5)O3—C201.433 (4)
O7—C361.362 (4)N3—C101.307 (5)
O7—C421.418 (4)N3—C111.372 (5)
N5—C311.336 (4)N1—C91.347 (4)
N5—C321.346 (5)N1—C51.429 (4)
C34—C331.403 (5)N1—H1N0.89 (3)
C34—C351.416 (5)C15—C161.364 (5)
C34—C311.431 (4)C15—C141.429 (5)
C37—C381.369 (5)C11—C121.402 (5)
C37—C361.431 (4)C11—C161.411 (5)
N6—C321.303 (5)C14—C131.360 (5)
N6—C331.377 (4)N2—C91.322 (5)
N4—C311.343 (4)N2—C101.340 (5)
N4—C291.439 (4)C16—H160.9300
N4—H4N0.71 (6)C5—C61.382 (5)
C39—C401.524 (5)C5—C41.390 (5)
C39—H39A0.9700C13—C121.414 (5)
C39—H39B0.9700C13—H130.9300
C35—C361.362 (5)O4—C221.392 (5)
C35—H350.9300O4—C211.402 (5)
C29—C281.377 (5)C17—C181.505 (5)
C29—C301.381 (5)C17—H17A0.9700
C33—C381.410 (5)C17—H17B0.9700
C26—C251.380 (5)C10—H100.9300
C26—C271.380 (6)C4—C31.398 (5)
C26—H260.9300C4—H40.9300
C24—C231.179 (6)C12—C91.427 (4)
C24—C251.446 (5)C20—C211.492 (5)
C28—C271.394 (5)C20—H20A0.9700
C28—H280.9300C20—H20B0.9700
C32—H320.9300O2—C191.394 (8)
C25—C301.405 (5)O2—C181.408 (6)
C38—H380.9300C3—C81.390 (6)
O6—C401.407 (5)C3—C21.444 (6)
O6—C411.418 (7)C8—C71.390 (6)
C27—H270.9300C8—H80.9300
C43—C421.502 (5)C2—C11.190 (6)
C43—H43A0.9700C21—H21A0.9700
C43—H43B0.9700C21—H21B0.9700
C42—H42A0.9700C6—C71.382 (6)
C42—H42B0.9700C6—H60.9300
C30—H300.9300C18—H18A0.9700
C23—H230.9300C18—H18B0.9700
C44—H44A0.9600C22—H22A0.9600
C44—H44B0.9600C22—H22B0.9600
C44—H44C0.9600C22—H22C0.9600
C41—H41A0.9600C7—H70.9300
C41—H41B0.9600C1—H10.9300
C41—H41C0.9600C19—H19A0.9600
C40—H40A0.9700C19—H19B0.9600
C40—H40B0.9700C19—H19C0.9600
C37—O5—C39119.1 (3)C15—O1—C17118.3 (3)
C43—O8—C44112.8 (3)C14—O3—C20117.7 (3)
C36—O7—C42118.6 (3)C10—N3—C11115.4 (3)
C31—N5—C32116.0 (3)C9—N1—C5122.9 (3)
C33—C34—C35119.3 (3)C9—N1—H1N130 (2)
C33—C34—C31116.8 (3)C5—N1—H1N107 (2)
C35—C34—C31123.9 (3)O1—C15—C16125.8 (3)
O5—C37—C38126.7 (3)O1—C15—C14113.9 (3)
O5—C37—C36113.5 (3)C16—C15—C14120.2 (3)
C38—C37—C36119.8 (3)N3—C11—C12121.8 (3)
C32—N6—C33116.1 (3)N3—C11—C16118.6 (3)
C31—N4—C29123.7 (3)C12—C11—C16119.6 (3)
C31—N4—H4N121 (4)O3—C14—C13126.1 (3)
C29—N4—H4N114 (4)O3—C14—C15113.5 (3)
O5—C39—C40106.3 (3)C13—C14—C15120.3 (3)
O5—C39—H39A110.5C9—N2—C10117.0 (3)
C40—C39—H39A110.5C15—C16—C11119.9 (3)
O5—C39—H39B110.5C15—C16—H16120.0
C40—C39—H39B110.5C11—C16—H16120.0
H39A—C39—H39B108.7C6—C5—C4120.7 (3)
C36—C35—C34120.2 (3)C6—C5—N1119.3 (3)
C36—C35—H35119.9C4—C5—N1120.0 (3)
C34—C35—H35119.9C14—C13—C12119.8 (3)
N5—C31—N4117.7 (3)C14—C13—H13120.1
N5—C31—C34121.3 (3)C12—C13—H13120.1
N4—C31—C34121.0 (3)C22—O4—C21112.9 (3)
C28—C29—C30120.2 (3)O1—C17—C18106.8 (3)
C28—C29—N4119.4 (3)O1—C17—H17A110.4
C30—C29—N4120.3 (3)C18—C17—H17A110.4
N6—C33—C34120.8 (3)O1—C17—H17B110.4
N6—C33—C38119.1 (3)C18—C17—H17B110.4
C34—C33—C38120.1 (3)H17A—C17—H17B108.6
C35—C36—O7126.7 (3)N3—C10—N2128.3 (3)
C35—C36—C37120.4 (3)N3—C10—H10115.8
O7—C36—C37112.8 (3)N2—C10—H10115.8
C25—C26—C27119.9 (3)C5—C4—C3120.0 (3)
C25—C26—H26120.0C5—C4—H4120.0
C27—C26—H26120.0C3—C4—H4120.0
C23—C24—C25178.7 (5)C11—C12—C13119.8 (3)
C29—C28—C27119.8 (3)C11—C12—C9116.1 (3)
C29—C28—H28120.1C13—C12—C9124.1 (3)
C27—C28—H28120.1N2—C9—N1118.1 (3)
N6—C32—N5128.9 (3)N2—C9—C12121.3 (3)
N6—C32—H32115.6N1—C9—C12120.6 (3)
N5—C32—H32115.6O3—C20—C21105.7 (3)
C26—C25—C30119.6 (3)O3—C20—H20A110.6
C26—C25—C24120.9 (3)C21—C20—H20A110.6
C30—C25—C24119.4 (3)O3—C20—H20B110.6
C37—C38—C33120.1 (3)C21—C20—H20B110.6
C37—C38—H38120.0H20A—C20—H20B108.7
C33—C38—H38120.0C19—O2—C18115.8 (4)
C40—O6—C41115.2 (4)C8—C3—C4119.3 (4)
C26—C27—C28120.5 (3)C8—C3—C2121.4 (4)
C26—C27—H27119.8C4—C3—C2119.3 (3)
C28—C27—H27119.8C7—C8—C3119.9 (3)
O8—C43—C42107.7 (3)C7—C8—H8120.0
O8—C43—H43A110.2C3—C8—H8120.0
C42—C43—H43A110.2C1—C2—C3178.8 (5)
O8—C43—H43B110.2O4—C21—C20109.1 (3)
C42—C43—H43B110.2O4—C21—H21A109.9
H43A—C43—H43B108.5C20—C21—H21A109.9
O7—C42—C43106.2 (3)O4—C21—H21B109.9
O7—C42—H42A110.5C20—C21—H21B109.9
C43—C42—H42A110.5H21A—C21—H21B108.3
O7—C42—H42B110.5C7—C6—C5119.3 (4)
C43—C42—H42B110.5C7—C6—H6120.4
H42A—C42—H42B108.7C5—C6—H6120.4
C29—C30—C25120.0 (3)O2—C18—C17113.1 (3)
C29—C30—H30120.0O2—C18—H18A109.0
C25—C30—H30120.0C17—C18—H18A109.0
C24—C23—H23180.0O2—C18—H18B109.0
O8—C44—H44A109.5C17—C18—H18B109.0
O8—C44—H44B109.5H18A—C18—H18B107.8
H44A—C44—H44B109.5O4—C22—H22A109.5
O8—C44—H44C109.5O4—C22—H22B109.5
H44A—C44—H44C109.5H22A—C22—H22B109.5
H44B—C44—H44C109.5O4—C22—H22C109.5
O6—C41—H41A109.5H22A—C22—H22C109.5
O6—C41—H41B109.5H22B—C22—H22C109.5
H41A—C41—H41B109.5C6—C7—C8120.9 (3)
O6—C41—H41C109.5C6—C7—H7119.5
H41A—C41—H41C109.5C8—C7—H7119.5
H41B—C41—H41C109.5C2—C1—H1180.0
O6—C40—C39113.5 (3)O2—C19—H19A109.5
O6—C40—H40A108.9O2—C19—H19B109.5
C39—C40—H40A108.9H19A—C19—H19B109.5
O6—C40—H40B108.9O2—C19—H19C109.5
C39—C40—H40B108.9H19A—C19—H19C109.5
H40A—C40—H40B107.7H19B—C19—H19C109.5
(Erlotinib-Adipic-adipate) top
Crystal data top
C28H33N3O8F(000) = 1144
Mr = 539.57Dx = 1.288 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 14.2922 (18) ÅCell parameters from 6695 reflections
b = 27.500 (3) Åθ = 2.1–27.5°
c = 7.0784 (7) ŵ = 0.10 mm1
β = 90.467 (7)°T = 150 K
V = 2781.9 (5) Å3Plate, colorless
Z = 40.40 × 0.16 × 0.12 mm
Data collection top
XtaLABmini
diffractometer
5057 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.149
Graphite monochromatorθmax = 27.5°, θmin = 1.4°
Absorption correction: multi-scan
SADABS
h = 1818
Tmin = 0.726, Tmax = 1.000k = 3535
29176 measured reflectionsl = 99
6367 independent reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.068Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.214H atoms treated by a mixture of independent and constrained refinement
S = 1.21 w = 1/[σ2(Fo2) + (0.0995P)2 + 0.1237P]
where P = (Fo2 + 2Fc2)/3
6367 reflections(Δ/σ)max < 0.001
364 parametersΔρmax = 0.34 e Å3
1 restraintΔρmin = 0.56 e Å3
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
H1N0.340 (2)0.8357 (11)0.660 (4)0.039 (8)*
H6A0.719 (2)0.0498 (11)0.275 (4)0.064 (10)*
O30.04861 (10)0.75280 (6)0.4445 (2)0.0271 (3)
O10.01645 (11)0.83843 (5)0.4921 (2)0.0264 (3)
N30.24537 (13)0.68126 (6)0.6438 (3)0.0246 (4)
N20.37561 (13)0.73013 (6)0.7215 (3)0.0262 (4)
O40.20501 (12)0.70438 (6)0.6411 (2)0.0357 (4)
C120.22842 (14)0.76779 (7)0.6218 (3)0.0214 (4)
O60.69370 (13)0.03167 (6)0.3742 (3)0.0388 (4)
C90.32543 (15)0.77037 (7)0.6775 (3)0.0226 (4)
N10.36946 (13)0.81340 (7)0.6904 (3)0.0267 (4)
C140.07888 (15)0.80221 (7)0.5294 (3)0.0225 (4)
C110.18968 (14)0.72122 (7)0.6026 (3)0.0216 (4)
C130.17020 (15)0.80882 (7)0.5850 (3)0.0224 (4)
H130.19410.84010.59870.027*
O50.66832 (14)0.10153 (6)0.5227 (2)0.0399 (4)
C100.33293 (16)0.68762 (8)0.7023 (3)0.0258 (4)
H100.36720.65990.73240.031*
C150.04116 (14)0.75406 (7)0.5049 (3)0.0220 (4)
O20.10566 (13)0.91124 (7)0.6479 (3)0.0440 (5)
C230.65674 (16)0.05742 (8)0.5104 (3)0.0283 (5)
C200.09043 (16)0.70596 (8)0.4001 (3)0.0278 (5)
H20A0.04440.68580.33770.033*
H20B0.14220.71080.31260.033*
C160.09666 (15)0.71421 (8)0.5440 (3)0.0239 (4)
H160.07260.68290.53160.029*
C80.48783 (15)0.86236 (8)0.8394 (3)0.0269 (5)
H80.44050.88280.88140.032*
C70.46592 (15)0.82111 (8)0.7329 (3)0.0252 (4)
C170.04491 (16)0.88742 (8)0.5360 (3)0.0293 (5)
H17A0.09560.89740.45430.035*
H17B0.06630.88950.66610.035*
C210.12547 (16)0.67977 (8)0.5720 (3)0.0298 (5)
H21A0.14180.64650.53960.036*
H21B0.07690.67890.66860.036*
C50.62875 (16)0.80098 (9)0.7144 (4)0.0345 (5)
H50.67590.78020.67400.041*
C250.53735 (18)0.01035 (9)0.5665 (4)0.0345 (5)
H25A0.57560.03330.49730.041*
H25B0.50690.02800.66760.041*
C60.53610 (16)0.79066 (8)0.6674 (3)0.0303 (5)
H60.52140.76380.59320.036*
C240.60091 (18)0.02895 (9)0.6527 (4)0.0370 (5)
H24A0.56250.05140.72380.044*
H24B0.64400.01360.74090.044*
C40.65180 (16)0.84140 (9)0.8198 (3)0.0348 (5)
H40.71410.84780.84910.042*
C30.58209 (16)0.87282 (9)0.8829 (3)0.0305 (5)
C180.03862 (18)0.91962 (8)0.5056 (4)0.0334 (5)
H18A0.01930.95340.50840.040*
H18B0.06620.91300.38260.040*
C20.60571 (18)0.91514 (9)0.9928 (4)0.0371 (6)
C10.6274 (2)0.94928 (11)1.0843 (4)0.0478 (7)
H10.64460.97621.15630.057*
C220.2441 (2)0.67984 (12)0.8000 (4)0.0530 (8)
H22A0.29790.69740.84330.080*
H22B0.19830.67810.89960.080*
H22C0.26240.64760.76360.080*
C190.1864 (2)0.94060 (11)0.6226 (5)0.0585 (8)
H19A0.23020.93390.72150.088*
H19B0.21480.93340.50240.088*
H19C0.16890.97430.62680.088*
O70.84952 (13)0.09803 (6)0.1179 (2)0.0373 (4)
O80.75517 (13)0.08462 (6)0.1214 (3)0.0398 (4)
C260.82373 (15)0.07292 (8)0.0187 (3)0.0264 (4)
C270.87779 (16)0.02642 (8)0.0659 (3)0.0298 (5)
H27A0.88610.02440.20180.036*
H27B0.84060.00130.02650.036*
C280.97366 (16)0.02302 (8)0.0269 (3)0.0311 (5)
H28A0.96560.02400.16300.037*
H28B1.01080.05100.01010.037*
H30.217 (3)0.6500 (13)0.635 (5)0.061 (10)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O30.0215 (7)0.0270 (8)0.0326 (8)0.0054 (6)0.0053 (6)0.0004 (6)
O10.0246 (8)0.0198 (7)0.0348 (8)0.0009 (6)0.0058 (6)0.0018 (6)
N30.0240 (9)0.0187 (8)0.0312 (9)0.0011 (7)0.0019 (7)0.0004 (7)
N20.0241 (9)0.0223 (9)0.0321 (9)0.0020 (7)0.0009 (7)0.0033 (7)
O40.0293 (9)0.0400 (10)0.0379 (9)0.0026 (7)0.0033 (7)0.0016 (7)
C120.0216 (10)0.0199 (9)0.0227 (9)0.0027 (7)0.0002 (7)0.0001 (7)
O60.0439 (10)0.0221 (8)0.0505 (10)0.0039 (7)0.0162 (8)0.0049 (7)
C90.0226 (10)0.0224 (10)0.0226 (9)0.0027 (8)0.0018 (8)0.0009 (8)
N10.0203 (9)0.0207 (9)0.0390 (10)0.0023 (7)0.0070 (8)0.0012 (8)
C140.0245 (10)0.0209 (10)0.0220 (9)0.0008 (8)0.0007 (8)0.0014 (7)
C110.0230 (10)0.0203 (9)0.0216 (9)0.0017 (8)0.0017 (8)0.0003 (7)
C130.0231 (10)0.0200 (9)0.0241 (9)0.0040 (8)0.0018 (8)0.0007 (8)
O50.0549 (12)0.0212 (8)0.0437 (9)0.0023 (7)0.0042 (8)0.0038 (7)
C100.0249 (11)0.0210 (10)0.0316 (10)0.0005 (8)0.0009 (8)0.0027 (8)
C150.0207 (10)0.0239 (10)0.0214 (9)0.0032 (8)0.0009 (7)0.0008 (8)
O20.0389 (10)0.0393 (10)0.0539 (11)0.0105 (8)0.0114 (8)0.0076 (8)
C230.0246 (11)0.0234 (11)0.0367 (11)0.0009 (8)0.0048 (9)0.0010 (9)
C200.0261 (11)0.0285 (11)0.0288 (10)0.0078 (9)0.0050 (9)0.0031 (9)
C160.0243 (10)0.0216 (10)0.0259 (9)0.0052 (8)0.0003 (8)0.0021 (8)
C80.0230 (11)0.0248 (10)0.0329 (11)0.0011 (8)0.0042 (8)0.0005 (9)
C70.0202 (10)0.0241 (10)0.0313 (10)0.0037 (8)0.0051 (8)0.0012 (8)
C170.0320 (12)0.0201 (10)0.0357 (11)0.0028 (9)0.0020 (9)0.0011 (9)
C210.0263 (11)0.0287 (11)0.0343 (11)0.0051 (9)0.0043 (9)0.0004 (9)
C50.0237 (11)0.0328 (12)0.0471 (13)0.0021 (9)0.0013 (10)0.0005 (10)
C250.0340 (12)0.0268 (11)0.0427 (12)0.0059 (9)0.0018 (10)0.0064 (10)
C60.0265 (11)0.0262 (11)0.0381 (12)0.0029 (9)0.0002 (9)0.0037 (9)
C240.0346 (13)0.0363 (13)0.0400 (13)0.0067 (10)0.0020 (10)0.0010 (10)
C40.0200 (11)0.0401 (13)0.0441 (13)0.0022 (10)0.0074 (9)0.0021 (11)
C30.0269 (11)0.0332 (12)0.0314 (11)0.0067 (9)0.0068 (9)0.0003 (9)
C180.0350 (13)0.0253 (11)0.0399 (12)0.0041 (9)0.0013 (10)0.0040 (9)
C20.0285 (12)0.0416 (14)0.0411 (13)0.0091 (10)0.0041 (10)0.0043 (11)
C10.0429 (16)0.0490 (16)0.0513 (15)0.0164 (13)0.0001 (12)0.0153 (13)
C220.0469 (17)0.068 (2)0.0440 (15)0.0087 (15)0.0127 (13)0.0090 (14)
C190.0398 (16)0.0465 (17)0.089 (2)0.0138 (13)0.0047 (16)0.0029 (16)
O70.0425 (10)0.0277 (8)0.0419 (9)0.0129 (7)0.0115 (8)0.0108 (7)
O80.0335 (10)0.0321 (9)0.0540 (11)0.0115 (7)0.0155 (8)0.0092 (8)
C260.0234 (10)0.0218 (10)0.0339 (11)0.0032 (8)0.0005 (9)0.0009 (8)
C270.0303 (12)0.0214 (10)0.0379 (11)0.0056 (9)0.0049 (9)0.0055 (9)
C280.0273 (11)0.0242 (11)0.0420 (12)0.0057 (9)0.0054 (10)0.0070 (9)
Geometric parameters (Å, º) top
O3—C151.350 (2)C17—C181.500 (3)
O3—C201.453 (2)C17—H17A0.9700
O1—C141.362 (3)C17—H17B0.9700
O1—C171.440 (2)C21—H21A0.9700
N3—C101.327 (3)C21—H21B0.9700
N3—C111.386 (3)C5—C41.377 (3)
N3—H30.95 (4)C5—C61.392 (3)
N2—C101.325 (3)C5—H50.9300
N2—C91.354 (3)C25—C25i1.528 (5)
O4—C211.414 (3)C25—C241.535 (3)
O4—C221.429 (3)C25—H25A0.9700
C12—C111.401 (3)C25—H25B0.9700
C12—C131.425 (3)C6—H60.9300
C12—C91.440 (3)C24—H24A0.9700
O6—C231.311 (3)C24—H24B0.9700
O6—H6A0.937 (18)C4—C31.395 (4)
C9—N11.343 (3)C4—H40.9300
N1—C71.425 (3)C3—C21.439 (3)
N1—H1N0.78 (3)C18—H18A0.9700
C14—C131.372 (3)C18—H18B0.9700
C14—C151.439 (3)C2—C11.180 (4)
C11—C161.403 (3)C1—H10.9300
C13—H130.9300C22—H22A0.9600
O5—C231.227 (3)C22—H22B0.9600
C10—H100.9300C22—H22C0.9600
C15—C161.380 (3)C19—H19A0.9600
O2—C181.415 (3)C19—H19B0.9600
O2—C191.419 (3)C19—H19C0.9600
C23—C241.509 (3)O7—C261.246 (3)
C20—C211.504 (3)O8—C261.266 (3)
C20—H20A0.9700C26—C271.529 (3)
C20—H20B0.9700C27—C281.527 (3)
C16—H160.9300C27—H27A0.9700
C8—C71.396 (3)C27—H27B0.9700
C8—C31.409 (3)C28—C28ii1.520 (4)
C8—H80.9300C28—H28A0.9700
C7—C61.389 (3)C28—H28B0.9700
C15—O3—C20118.67 (17)C20—C21—H21B109.9
C14—O1—C17117.33 (17)H21A—C21—H21B108.3
C10—N3—C11119.99 (18)C4—C5—C6121.1 (2)
C10—N3—H3123 (2)C4—C5—H5119.4
C11—N3—H3117 (2)C6—C5—H5119.4
C10—N2—C9117.05 (18)C25i—C25—C24113.0 (2)
C21—O4—C22111.5 (2)C25i—C25—H25A109.0
C11—C12—C13118.45 (19)C24—C25—H25A109.0
C11—C12—C9116.76 (18)C25i—C25—H25B109.0
C13—C12—C9124.79 (18)C24—C25—H25B109.0
C23—O6—H6A115 (2)H25A—C25—H25B107.8
N1—C9—N2117.22 (19)C7—C6—C5119.0 (2)
N1—C9—C12120.77 (18)C7—C6—H6120.5
N2—C9—C12122.00 (18)C5—C6—H6120.5
C9—N1—C7126.70 (19)C23—C24—C25114.5 (2)
C9—N1—H1N115 (2)C23—C24—H24A108.6
C7—N1—H1N118 (2)C25—C24—H24A108.6
O1—C14—C13125.36 (19)C23—C24—H24B108.6
O1—C14—C15113.92 (18)C25—C24—H24B108.6
C13—C14—C15120.71 (18)H24A—C24—H24B107.6
N3—C11—C12118.57 (18)C5—C4—C3120.3 (2)
N3—C11—C16119.62 (18)C5—C4—H4119.8
C12—C11—C16121.81 (19)C3—C4—H4119.8
C14—C13—C12120.01 (18)C4—C3—C8119.2 (2)
C14—C13—H13120.0C4—C3—C2120.6 (2)
C12—C13—H13120.0C8—C3—C2120.2 (2)
N2—C10—N3125.5 (2)O2—C18—C17110.14 (19)
N2—C10—H10117.3O2—C18—H18A109.6
N3—C10—H10117.3C17—C18—H18A109.6
O3—C15—C16125.92 (18)O2—C18—H18B109.6
O3—C15—C14114.58 (18)C17—C18—H18B109.6
C16—C15—C14119.51 (18)H18A—C18—H18B108.1
C18—O2—C19111.9 (2)C1—C2—C3178.1 (3)
O5—C23—O6122.1 (2)C2—C1—H1180.0
O5—C23—C24122.5 (2)O4—C22—H22A109.5
O6—C23—C24115.4 (2)O4—C22—H22B109.5
O3—C20—C21112.85 (17)H22A—C22—H22B109.5
O3—C20—H20A109.0O4—C22—H22C109.5
C21—C20—H20A109.0H22A—C22—H22C109.5
O3—C20—H20B109.0H22B—C22—H22C109.5
C21—C20—H20B109.0O2—C19—H19A109.5
H20A—C20—H20B107.8O2—C19—H19B109.5
C15—C16—C11119.47 (19)H19A—C19—H19B109.5
C15—C16—H16120.3O2—C19—H19C109.5
C11—C16—H16120.3H19A—C19—H19C109.5
C7—C8—C3119.6 (2)H19B—C19—H19C109.5
C7—C8—H8120.2O7—C26—O8122.7 (2)
C3—C8—H8120.2O7—C26—C27118.71 (19)
C6—C7—C8120.7 (2)O8—C26—C27118.63 (19)
C6—C7—N1122.67 (19)C28—C27—C26114.27 (18)
C8—C7—N1116.58 (19)C28—C27—H27A108.7
O1—C17—C18107.35 (18)C26—C27—H27A108.7
O1—C17—H17A110.2C28—C27—H27B108.7
C18—C17—H17A110.2C26—C27—H27B108.7
O1—C17—H17B110.2H27A—C27—H27B107.6
C18—C17—H17B110.2C28ii—C28—C27112.8 (2)
H17A—C17—H17B108.5C28ii—C28—H28A109.0
O4—C21—C20108.93 (19)C27—C28—H28A109.0
O4—C21—H21A109.9C28ii—C28—H28B109.0
C20—C21—H21A109.9C27—C28—H28B109.0
O4—C21—H21B109.9H28A—C28—H28B107.8
Symmetry codes: (i) x+1, y, z+1; (ii) x+2, y, z.
(Erlotinib-glutaric-hydrate) top
Crystal data top
C27H33N3O9Z = 2
Mr = 543.56F(000) = 576
Triclinic, P1Dx = 1.310 Mg m3
a = 7.916 (10) ÅMo Kα radiation, λ = 0.71073 Å
b = 14.012 (15) ÅCell parameters from 3232 reflections
c = 14.349 (14) Åθ = 1.7–27.5°
α = 61.73 (3)°µ = 0.10 mm1
β = 79.64 (6)°T = 150 K
γ = 86.58 (6)°Plate, colorless
V = 1378 (3) Å30.30 × 0.20 × 0.16 mm
Data collection top
XtaLABmini
diffractometer
4171 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.076
Graphite monochromatorθmax = 27.5°, θmin = 1.6°
Absorption correction: multi-scan
SADABS
h = 1010
Tmin = 0.626, Tmax = 1.000k = 1817
14359 measured reflectionsl = 1818
6237 independent reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.067Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.197H atoms treated by a mixture of independent and constrained refinement
S = 1.13 w = 1/[σ2(Fo2) + (0.0735P)2]
where P = (Fo2 + 2Fc2)/3
6237 reflections(Δ/σ)max < 0.001
372 parametersΔρmax = 0.41 e Å3
0 restraintsΔρmin = 0.43 e Å3
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O90.6897 (3)0.55637 (18)0.7932 (2)0.0439 (5)
H10.818 (4)0.063 (2)1.123 (2)0.037 (8)*
H9B0.676 (5)0.532 (3)0.755 (3)0.065 (13)*
H5A0.208 (6)0.677 (4)0.741 (4)0.108 (16)*
H70.569 (6)1.023 (4)0.704 (4)0.122 (18)*
H9A0.731 (6)0.512 (4)0.855 (4)0.105 (17)*
O30.6315 (2)0.29470 (13)0.96416 (13)0.0283 (4)
O10.5331 (2)0.35140 (13)0.78200 (13)0.0280 (4)
N30.6549 (3)0.00483 (16)0.81022 (16)0.0276 (5)
N10.8333 (3)0.10565 (17)1.09636 (17)0.0260 (5)
O80.2608 (2)1.00671 (15)0.74993 (14)0.0370 (5)
O20.6014 (2)0.56656 (14)0.60101 (16)0.0385 (5)
C150.5867 (3)0.24694 (19)0.83196 (18)0.0239 (5)
N20.7825 (3)0.13877 (17)0.95800 (16)0.0286 (5)
C120.7129 (3)0.03773 (19)0.94816 (18)0.0232 (5)
C90.7768 (3)0.07130 (19)1.00088 (19)0.0235 (5)
C110.6531 (3)0.06786 (19)0.85080 (18)0.0232 (5)
C130.7060 (3)0.11384 (19)0.98769 (18)0.0241 (5)
H130.74330.09431.05210.029*
O50.1874 (3)0.75208 (18)0.72299 (19)0.0486 (6)
C140.6447 (3)0.21615 (19)0.93213 (18)0.0235 (5)
O40.7701 (3)0.45364 (16)1.00005 (16)0.0442 (5)
O70.5184 (2)1.02943 (17)0.64482 (15)0.0397 (5)
C100.7184 (3)0.1015 (2)0.8653 (2)0.0289 (6)
H100.71920.14940.83740.035*
C70.8964 (3)0.20770 (19)1.16541 (19)0.0249 (5)
C160.5902 (3)0.17279 (19)0.79367 (18)0.0250 (5)
H160.55100.19210.72990.030*
C170.4837 (3)0.3873 (2)0.67766 (18)0.0267 (5)
H17A0.38360.34590.68520.032*
H17B0.57680.37720.62930.032*
O60.0817 (3)0.69073 (16)0.72288 (16)0.0447 (5)
C270.3497 (3)1.02208 (19)0.6640 (2)0.0296 (6)
C230.0179 (4)0.7640 (2)0.7093 (2)0.0349 (6)
C60.9106 (3)0.2995 (2)1.1493 (2)0.0291 (5)
H60.87790.29681.08910.035*
C80.9480 (3)0.21326 (19)1.25665 (19)0.0260 (5)
H80.94010.15241.26710.031*
C41.0249 (3)0.4013 (2)1.3158 (2)0.0313 (6)
H41.06710.46531.36510.038*
C21.0618 (3)0.3120 (2)1.4254 (2)0.0332 (6)
C200.6964 (3)0.2677 (2)1.0623 (2)0.0312 (6)
H20A0.81790.25281.05360.037*
H20B0.63600.20371.12170.037*
C210.6686 (4)0.3626 (2)1.0848 (2)0.0356 (6)
H21A0.54810.38031.08890.043*
H21B0.70190.34441.15300.043*
C31.0112 (3)0.3095 (2)1.33222 (19)0.0283 (5)
C50.9747 (3)0.3953 (2)1.2249 (2)0.0325 (6)
H50.98390.45591.21410.039*
C180.4434 (3)0.5060 (2)0.6339 (2)0.0306 (6)
H18A0.38460.52910.57320.037*
H18B0.36930.51790.68880.037*
C240.0385 (4)0.8795 (2)0.6756 (2)0.0396 (7)
H24A0.05130.92820.64420.048*
H24B0.05240.88440.73900.048*
C250.2054 (4)0.9167 (2)0.5954 (2)0.0380 (6)
H25A0.18800.91920.52900.046*
H25B0.29240.86400.62360.046*
C11.1019 (4)0.3133 (2)1.5021 (2)0.0454 (7)
H1A1.13330.31431.56200.054*
C260.2715 (4)1.0300 (2)0.5705 (2)0.0354 (6)
H26A0.35751.05860.50570.043*
H26B0.17711.07940.55830.043*
C190.5762 (4)0.6811 (2)0.5565 (3)0.0504 (8)
H19A0.68540.71840.53560.076*
H19B0.50480.69610.60930.076*
H19C0.52170.70550.49470.076*
C220.7798 (5)0.5397 (3)1.0267 (3)0.0538 (9)
H22A0.84890.59890.96810.081*
H22B0.83070.51371.09000.081*
H22C0.66630.56401.03970.081*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O90.0522 (13)0.0381 (12)0.0477 (14)0.0025 (10)0.0159 (11)0.0230 (11)
O30.0393 (10)0.0264 (9)0.0239 (9)0.0077 (8)0.0144 (8)0.0132 (7)
O10.0370 (9)0.0240 (9)0.0230 (9)0.0068 (7)0.0141 (7)0.0086 (7)
N30.0298 (11)0.0294 (11)0.0241 (11)0.0003 (9)0.0054 (9)0.0127 (9)
N10.0331 (11)0.0203 (10)0.0250 (11)0.0051 (9)0.0108 (9)0.0095 (9)
O80.0433 (11)0.0422 (11)0.0276 (10)0.0081 (9)0.0072 (9)0.0185 (9)
O20.0391 (10)0.0240 (9)0.0440 (12)0.0031 (8)0.0126 (9)0.0077 (8)
C150.0238 (11)0.0237 (12)0.0206 (12)0.0005 (10)0.0054 (9)0.0071 (10)
N20.0319 (11)0.0283 (11)0.0268 (11)0.0035 (9)0.0082 (9)0.0131 (9)
C120.0226 (11)0.0256 (12)0.0180 (11)0.0023 (10)0.0027 (9)0.0076 (10)
C90.0215 (11)0.0243 (12)0.0224 (12)0.0012 (9)0.0026 (9)0.0093 (10)
C110.0226 (11)0.0261 (12)0.0208 (12)0.0016 (10)0.0024 (9)0.0111 (10)
C130.0254 (11)0.0262 (12)0.0198 (12)0.0001 (10)0.0060 (10)0.0093 (10)
O50.0437 (12)0.0396 (12)0.0697 (16)0.0007 (10)0.0108 (11)0.0312 (11)
C140.0251 (11)0.0235 (12)0.0215 (12)0.0016 (10)0.0053 (10)0.0100 (10)
O40.0624 (13)0.0339 (10)0.0464 (12)0.0002 (10)0.0165 (10)0.0246 (10)
O70.0385 (11)0.0549 (13)0.0279 (10)0.0011 (9)0.0081 (9)0.0201 (9)
C100.0328 (13)0.0299 (13)0.0286 (13)0.0009 (11)0.0060 (11)0.0173 (11)
C70.0226 (11)0.0241 (12)0.0239 (12)0.0005 (10)0.0043 (10)0.0078 (10)
C160.0249 (11)0.0285 (12)0.0191 (12)0.0016 (10)0.0057 (10)0.0084 (10)
C170.0313 (12)0.0279 (12)0.0184 (12)0.0031 (10)0.0099 (10)0.0073 (10)
O60.0519 (12)0.0393 (11)0.0443 (12)0.0092 (10)0.0197 (10)0.0178 (10)
C270.0398 (14)0.0197 (12)0.0277 (14)0.0047 (11)0.0116 (12)0.0083 (10)
C230.0452 (16)0.0368 (15)0.0275 (14)0.0019 (13)0.0095 (12)0.0179 (12)
C60.0293 (12)0.0275 (13)0.0291 (13)0.0016 (11)0.0079 (11)0.0112 (11)
C80.0255 (12)0.0239 (12)0.0276 (13)0.0023 (10)0.0066 (10)0.0109 (10)
C40.0314 (13)0.0215 (12)0.0350 (14)0.0052 (10)0.0096 (11)0.0075 (11)
C20.0363 (14)0.0285 (13)0.0344 (15)0.0093 (11)0.0129 (12)0.0132 (12)
C200.0415 (14)0.0316 (13)0.0242 (13)0.0060 (12)0.0165 (11)0.0131 (11)
C210.0454 (15)0.0366 (14)0.0325 (15)0.0102 (13)0.0161 (12)0.0205 (12)
C30.0256 (12)0.0289 (13)0.0236 (13)0.0039 (10)0.0053 (10)0.0069 (10)
C50.0350 (13)0.0244 (12)0.0392 (15)0.0045 (11)0.0089 (12)0.0155 (12)
C180.0356 (13)0.0280 (13)0.0252 (13)0.0057 (11)0.0121 (11)0.0084 (11)
C240.0459 (16)0.0362 (15)0.0391 (16)0.0006 (13)0.0069 (13)0.0197 (13)
C250.0459 (16)0.0417 (16)0.0304 (15)0.0003 (13)0.0080 (12)0.0196 (13)
C10.0569 (18)0.0459 (17)0.0387 (17)0.0214 (15)0.0234 (15)0.0214 (14)
C260.0422 (15)0.0375 (15)0.0249 (14)0.0014 (12)0.0111 (12)0.0115 (12)
C190.063 (2)0.0243 (14)0.055 (2)0.0015 (14)0.0204 (17)0.0081 (13)
C220.070 (2)0.0415 (17)0.073 (2)0.0121 (16)0.0379 (19)0.0388 (17)
Geometric parameters (Å, º) top
O9—H9B0.80 (4)C17—H17B0.9700
O9—H9A0.91 (5)O6—C231.217 (3)
O3—C141.372 (3)C27—C261.531 (4)
O3—C201.456 (3)C23—C241.524 (4)
O1—C151.370 (3)C6—C51.405 (4)
O1—C171.456 (3)C6—H60.9300
N3—C101.327 (3)C8—C31.405 (3)
N3—C111.391 (3)C8—H80.9300
N1—C91.371 (3)C4—C51.395 (4)
N1—C71.423 (3)C4—C31.407 (4)
N1—H10.83 (3)C4—H40.9300
O8—C271.231 (3)C2—C11.192 (4)
O2—C181.429 (4)C2—C31.448 (4)
O2—C191.435 (4)C20—C211.505 (4)
C15—C161.383 (4)C20—H20A0.9700
C15—C141.446 (3)C20—H20B0.9700
N2—C91.345 (3)C21—H21A0.9700
N2—C101.361 (3)C21—H21B0.9700
C12—C131.420 (3)C5—H50.9300
C12—C111.417 (3)C18—H18A0.9700
C12—C91.453 (4)C18—H18B0.9700
C11—C161.414 (4)C24—C251.519 (4)
C13—C141.378 (3)C24—H24A0.9700
C13—H130.9300C24—H24B0.9700
O5—C231.329 (4)C25—C261.555 (4)
O5—H5A0.97 (5)C25—H25A0.9700
O4—C211.433 (4)C25—H25B0.9700
O4—C221.437 (4)C1—H1A0.9300
O7—C271.314 (4)C26—H26A0.9700
O7—H70.97 (5)C26—H26B0.9700
C10—H100.9300C19—H19A0.9600
C7—C81.406 (4)C19—H19B0.9600
C7—C61.405 (4)C19—H19C0.9600
C16—H160.9300C22—H22A0.9600
C17—C181.510 (4)C22—H22B0.9600
C17—H17A0.9700C22—H22C0.9600
H9B—O9—H9A119 (4)C5—C4—H4120.3
C14—O3—C20116.17 (19)C3—C4—H4120.3
C15—O1—C17116.32 (18)C1—C2—C3179.3 (3)
C10—N3—C11117.0 (2)O3—C20—C21108.3 (2)
C9—N1—C7130.4 (2)O3—C20—H20A110.0
C9—N1—H1116 (2)C21—C20—H20A110.0
C7—N1—H1113 (2)O3—C20—H20B110.0
C18—O2—C19112.4 (2)C21—C20—H20B110.0
O1—C15—C16125.5 (2)H20A—C20—H20B108.4
O1—C15—C14114.8 (2)O4—C21—C20108.9 (2)
C16—C15—C14119.7 (2)O4—C21—H21A109.9
C9—N2—C10116.6 (2)C20—C21—H21A109.9
C13—C12—C11119.0 (2)O4—C21—H21B109.9
C13—C12—C9124.7 (2)C20—C21—H21B109.9
C11—C12—C9116.4 (2)H21A—C21—H21B108.3
N2—C9—N1119.4 (2)C8—C3—C4119.6 (2)
N2—C9—C12121.6 (2)C8—C3—C2119.1 (2)
N1—C9—C12119.0 (2)C4—C3—C2121.3 (2)
N3—C11—C16119.1 (2)C4—C5—C6121.3 (2)
N3—C11—C12120.8 (2)C4—C5—H5119.3
C16—C11—C12120.1 (2)C6—C5—H5119.3
C14—C13—C12121.0 (2)O2—C18—C17108.3 (2)
C14—C13—H13119.5O2—C18—H18A110.0
C12—C13—H13119.5C17—C18—H18A110.0
C23—O5—H5A105 (3)O2—C18—H18B110.0
O3—C14—C13125.3 (2)C17—C18—H18B110.0
O3—C14—C15115.0 (2)H18A—C18—H18B108.4
C13—C14—C15119.7 (2)C25—C24—C23113.5 (2)
C21—O4—C22112.1 (2)C25—C24—H24A108.9
C27—O7—H7115 (3)C23—C24—H24A108.9
N3—C10—N2127.5 (2)C25—C24—H24B108.9
N3—C10—H10116.2C23—C24—H24B108.9
N2—C10—H10116.2H24A—C24—H24B107.7
C8—C7—C6119.3 (2)C24—C25—C26113.0 (2)
C8—C7—N1114.9 (2)C24—C25—H25A109.0
C6—C7—N1125.8 (2)C26—C25—H25A109.0
C15—C16—C11120.5 (2)C24—C25—H25B109.0
C15—C16—H16119.8C26—C25—H25B109.0
C11—C16—H16119.8H25A—C25—H25B107.8
O1—C17—C18107.3 (2)C2—C1—H1A180.0
O1—C17—H17A110.3C27—C26—C25110.7 (2)
C18—C17—H17A110.3C27—C26—H26A109.5
O1—C17—H17B110.3C25—C26—H26A109.5
C18—C17—H17B110.3C27—C26—H26B109.5
H17A—C17—H17B108.5C25—C26—H26B109.5
O8—C27—O7123.9 (2)H26A—C26—H26B108.1
O8—C27—C26122.2 (2)O2—C19—H19A109.5
O7—C27—C26113.8 (2)O2—C19—H19B109.5
O6—C23—O5123.9 (3)H19A—C19—H19B109.5
O6—C23—C24123.5 (3)O2—C19—H19C109.5
O5—C23—C24112.6 (2)H19A—C19—H19C109.5
C7—C6—C5119.5 (2)H19B—C19—H19C109.5
C7—C6—H6120.2O4—C22—H22A109.5
C5—C6—H6120.2O4—C22—H22B109.5
C7—C8—C3120.9 (2)H22A—C22—H22B109.5
C7—C8—H8119.6O4—C22—H22C109.5
C3—C8—H8119.6H22A—C22—H22C109.5
C5—C4—C3119.4 (2)H22B—C22—H22C109.5
(Erlotinib-succinic-hydrate) top
Crystal data top
C26H31N3O9F(000) = 1120
Mr = 529.54Dx = 1.346 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 13.4269 (16) ÅCell parameters from 6664 reflections
b = 24.169 (3) Åθ = 2.3–27.5°
c = 8.0606 (8) ŵ = 0.10 mm1
β = 92.410 (5)°T = 150 K
V = 2613.5 (5) Å3Plate, colorless
Z = 40.40 × 0.20 × 0.10 mm
Data collection top
XtaLABmini
diffractometer
4111 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.152
Graphite monochromatorθmax = 27.5°, θmin = 1.5°
Absorption correction: multi-scan
SADABS
h = 1717
Tmin = 0.478, Tmax = 1.000k = 3131
25590 measured reflectionsl = 1010
5991 independent reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.065Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.207H atoms treated by a mixture of independent and constrained refinement
S = 0.97 w = 1/[σ2(Fo2) + (0.0957P)2]
where P = (Fo2 + 2Fc2)/3
5991 reflections(Δ/σ)max < 0.001
367 parametersΔρmax = 0.59 e Å3
0 restraintsΔρmin = 0.62 e Å3
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
H10.524 (3)0.2284 (15)1.326 (4)0.053 (9)*
H8A0.639 (4)0.651 (2)0.459 (6)0.093 (15)*
H1A0.490 (2)0.4396 (13)0.844 (4)0.038 (8)*
H6A0.907 (3)0.6430 (18)0.242 (5)0.069 (12)*
H9A0.056 (3)0.6361 (19)0.605 (5)0.070 (13)*
H9B0.037 (3)0.589 (2)0.705 (5)0.079 (13)*
O10.23945 (12)0.61475 (6)0.4591 (2)0.0292 (4)
O30.20482 (11)0.52323 (6)0.6118 (2)0.0285 (4)
N30.59253 (14)0.59839 (8)0.5888 (2)0.0276 (4)
N20.65381 (14)0.52432 (8)0.7627 (2)0.0288 (4)
O70.63193 (14)0.61852 (7)0.1826 (2)0.0417 (5)
C140.30228 (16)0.53873 (9)0.6127 (3)0.0247 (4)
C120.47799 (16)0.52929 (9)0.6853 (3)0.0232 (4)
C100.66287 (17)0.57039 (10)0.6723 (3)0.0295 (5)
H100.72710.58460.66770.035*
N10.54851 (14)0.45464 (8)0.8511 (2)0.0248 (4)
O20.09868 (14)0.70254 (8)0.4636 (2)0.0426 (5)
C110.49703 (16)0.57823 (9)0.5971 (3)0.0238 (4)
C90.56223 (16)0.50246 (9)0.7669 (3)0.0235 (4)
O40.02620 (12)0.51222 (8)0.7678 (3)0.0398 (4)
C60.72089 (17)0.42703 (10)0.9438 (3)0.0291 (5)
H60.74900.45670.88910.035*
O80.66565 (16)0.67408 (8)0.3992 (2)0.0424 (5)
C70.61776 (16)0.41961 (9)0.9375 (3)0.0239 (4)
O60.85498 (16)0.65925 (9)0.2278 (3)0.0450 (5)
C130.37889 (16)0.50980 (9)0.6910 (3)0.0248 (4)
H130.36550.47730.74790.030*
C200.18277 (17)0.47441 (10)0.7053 (3)0.0311 (5)
H20A0.20570.47890.82020.037*
H20B0.21620.44260.65990.037*
C150.32198 (16)0.58890 (9)0.5261 (3)0.0245 (4)
C160.41793 (17)0.60780 (9)0.5166 (3)0.0258 (5)
H160.43090.63990.45750.031*
C30.63817 (17)0.33729 (9)1.1080 (3)0.0271 (5)
C80.57718 (16)0.37486 (9)1.0196 (3)0.0253 (4)
H80.50840.36991.01550.030*
C170.25426 (18)0.66715 (9)0.3801 (3)0.0306 (5)
H17A0.29660.66280.28640.037*
H17B0.28600.69290.45780.037*
C260.66898 (17)0.66003 (9)0.2427 (3)0.0308 (5)
C20.59367 (18)0.29179 (10)1.1932 (3)0.0318 (5)
C210.07192 (18)0.46596 (10)0.6945 (3)0.0346 (6)
H21A0.04890.46240.57930.041*
H21B0.05460.43240.75250.041*
C40.74181 (18)0.34489 (10)1.1147 (3)0.0320 (5)
H40.78340.32031.17320.038*
C180.15364 (19)0.68839 (10)0.3226 (3)0.0338 (5)
H18A0.16120.72070.25280.041*
H18B0.11830.66020.25780.041*
O90.02699 (17)0.62280 (11)0.6818 (4)0.0574 (6)
C50.78131 (18)0.38981 (11)1.0324 (3)0.0328 (5)
H50.85000.39511.03680.039*
C10.5566 (2)0.25471 (12)1.2644 (4)0.0415 (6)
O50.8929 (2)0.64474 (11)0.0423 (3)0.0680 (7)
C230.8361 (2)0.66106 (11)0.0665 (3)0.0430 (7)
C220.0755 (2)0.50171 (15)0.8004 (4)0.0516 (8)
H22A0.10390.53380.85010.077*
H22B0.07950.47090.87490.077*
H22C0.11160.49330.69820.077*
C250.7183 (3)0.70376 (14)0.1384 (4)0.0523 (7)
H25A0.67710.73670.13690.063*
H25B0.78200.71340.19190.063*
C240.7356 (3)0.68695 (16)0.0397 (4)0.0566 (8)
H24A0.68410.66090.07540.068*
H24B0.72850.71950.10980.068*
C190.0063 (3)0.72810 (18)0.4159 (5)0.0663 (10)
H19A0.02900.73730.51340.100*
H19B0.03310.70310.34800.100*
H19C0.01870.76120.35430.100*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0272 (8)0.0229 (8)0.0372 (9)0.0005 (6)0.0001 (7)0.0056 (7)
O30.0207 (7)0.0246 (8)0.0400 (9)0.0035 (6)0.0006 (7)0.0081 (7)
N30.0264 (9)0.0238 (9)0.0329 (10)0.0052 (7)0.0045 (8)0.0007 (8)
N20.0229 (9)0.0277 (10)0.0359 (10)0.0054 (7)0.0021 (8)0.0000 (8)
O70.0419 (10)0.0337 (10)0.0487 (11)0.0107 (8)0.0096 (9)0.0054 (8)
C140.0233 (10)0.0242 (10)0.0268 (10)0.0021 (8)0.0020 (8)0.0019 (9)
C120.0239 (10)0.0211 (10)0.0247 (10)0.0008 (8)0.0041 (8)0.0042 (8)
C100.0227 (10)0.0291 (11)0.0368 (12)0.0054 (8)0.0038 (9)0.0001 (9)
N10.0203 (9)0.0237 (9)0.0306 (9)0.0019 (7)0.0012 (7)0.0011 (7)
O20.0454 (11)0.0421 (11)0.0405 (10)0.0197 (8)0.0027 (8)0.0036 (8)
C110.0242 (10)0.0227 (10)0.0251 (10)0.0019 (8)0.0062 (8)0.0046 (8)
C90.0242 (10)0.0229 (10)0.0236 (10)0.0016 (8)0.0042 (8)0.0040 (8)
O40.0199 (8)0.0408 (10)0.0593 (11)0.0030 (7)0.0076 (8)0.0070 (9)
C60.0244 (11)0.0294 (11)0.0336 (12)0.0011 (8)0.0027 (9)0.0004 (9)
O80.0551 (12)0.0303 (10)0.0427 (11)0.0139 (8)0.0119 (9)0.0030 (8)
C70.0229 (10)0.0260 (11)0.0230 (10)0.0012 (8)0.0016 (8)0.0033 (8)
O60.0364 (11)0.0551 (13)0.0436 (11)0.0055 (9)0.0010 (9)0.0009 (9)
C130.0246 (10)0.0211 (10)0.0288 (11)0.0003 (8)0.0030 (9)0.0002 (8)
C200.0247 (11)0.0257 (11)0.0427 (13)0.0034 (8)0.0001 (10)0.0105 (10)
C150.0261 (11)0.0218 (10)0.0256 (10)0.0024 (8)0.0023 (9)0.0020 (8)
C160.0302 (11)0.0206 (10)0.0267 (11)0.0024 (8)0.0045 (9)0.0006 (8)
C30.0301 (11)0.0240 (11)0.0270 (10)0.0007 (8)0.0005 (9)0.0022 (9)
C80.0257 (10)0.0250 (10)0.0251 (10)0.0000 (8)0.0008 (9)0.0032 (8)
C170.0348 (12)0.0229 (11)0.0339 (12)0.0014 (9)0.0003 (10)0.0036 (9)
C260.0246 (11)0.0260 (11)0.0417 (13)0.0007 (8)0.0008 (10)0.0047 (10)
C20.0337 (12)0.0288 (12)0.0326 (12)0.0039 (9)0.0020 (10)0.0001 (10)
C210.0268 (12)0.0286 (12)0.0480 (14)0.0074 (9)0.0037 (10)0.0091 (10)
C40.0301 (12)0.0332 (12)0.0325 (12)0.0072 (9)0.0028 (10)0.0008 (10)
C180.0398 (13)0.0288 (12)0.0326 (12)0.0044 (10)0.0002 (10)0.0027 (10)
O90.0424 (12)0.0489 (14)0.0818 (18)0.0049 (10)0.0142 (12)0.0157 (13)
C50.0240 (11)0.0382 (13)0.0360 (12)0.0013 (9)0.0003 (9)0.0006 (10)
C10.0450 (15)0.0346 (14)0.0452 (14)0.0010 (11)0.0047 (12)0.0081 (12)
O50.0857 (19)0.0609 (15)0.0559 (13)0.0115 (13)0.0136 (13)0.0118 (12)
C230.0549 (17)0.0329 (13)0.0408 (14)0.0180 (12)0.0023 (13)0.0080 (11)
C220.0227 (12)0.074 (2)0.0581 (18)0.0052 (12)0.0062 (12)0.0202 (16)
C250.0584 (19)0.0439 (16)0.0554 (17)0.0144 (14)0.0136 (15)0.0054 (14)
C240.0525 (18)0.070 (2)0.0483 (17)0.0063 (16)0.0092 (14)0.0078 (16)
C190.056 (2)0.080 (3)0.064 (2)0.0369 (18)0.0022 (17)0.0089 (19)
Geometric parameters (Å, º) top
O1—C151.364 (3)C15—C161.372 (3)
O1—C171.435 (3)C16—H160.9300
O3—C141.361 (3)C3—C81.398 (3)
O3—C201.438 (3)C3—C41.402 (3)
N3—C101.323 (3)C3—C21.440 (3)
N3—C111.376 (3)C8—H80.9300
N2—C101.339 (3)C17—C181.500 (3)
N2—C91.340 (3)C17—H17A0.9700
O7—C261.212 (3)C17—H17B0.9700
C14—C131.375 (3)C26—C251.520 (4)
C14—C151.429 (3)C2—C11.185 (4)
C12—C111.409 (3)C21—H21A0.9700
C12—C131.414 (3)C21—H21B0.9700
C12—C91.439 (3)C4—C51.389 (4)
C10—H100.9300C4—H40.9300
N1—C91.357 (3)C18—H18A0.9700
N1—C71.419 (3)C18—H18B0.9700
N1—H1A0.87 (3)O9—H9A0.82 (5)
O2—C181.423 (3)O9—H9B0.86 (5)
O2—C191.424 (3)C5—H50.9300
C11—C161.415 (3)C1—H10.93 (4)
O4—C211.417 (3)O5—C231.204 (4)
O4—C221.424 (3)C23—C241.511 (5)
C6—C51.389 (3)C22—H22A0.9600
C6—C71.395 (3)C22—H22B0.9600
C6—H60.9300C22—H22C0.9600
O8—C261.309 (3)C25—C241.520 (5)
O8—H8A0.82 (5)C25—H25A0.9700
C7—C81.391 (3)C25—H25B0.9700
O6—C231.336 (4)C24—H24A0.9700
O6—H6A0.82 (4)C24—H24B0.9700
C13—H130.9300C19—H19A0.9600
C20—C211.501 (3)C19—H19B0.9600
C20—H20A0.9700C19—H19C0.9600
C20—H20B0.9700
C15—O1—C17117.04 (17)C18—C17—H17A110.2
C14—O3—C20116.25 (17)O1—C17—H17B110.2
C10—N3—C11116.16 (19)C18—C17—H17B110.2
C10—N2—C9116.50 (19)H17A—C17—H17B108.5
O3—C14—C13124.3 (2)O7—C26—O8124.8 (2)
O3—C14—C15115.38 (18)O7—C26—C25122.4 (2)
C13—C14—C15120.4 (2)O8—C26—C25112.7 (2)
C11—C12—C13119.2 (2)C1—C2—C3179.3 (3)
C11—C12—C9116.95 (19)O4—C21—C20108.32 (19)
C13—C12—C9123.9 (2)O4—C21—H21A110.0
N3—C10—N2128.5 (2)C20—C21—H21A110.0
N3—C10—H10115.7O4—C21—H21B110.0
N2—C10—H10115.7C20—C21—H21B110.0
C9—N1—C7130.85 (19)H21A—C21—H21B108.4
C9—N1—H1A118 (2)C5—C4—C3118.8 (2)
C7—N1—H1A111 (2)C5—C4—H4120.6
C18—O2—C19111.3 (2)C3—C4—H4120.6
N3—C11—C12120.7 (2)O2—C18—C17109.01 (19)
N3—C11—C16118.8 (2)O2—C18—H18A109.9
C12—C11—C16120.46 (19)C17—C18—H18A109.9
N2—C9—N1119.5 (2)O2—C18—H18B109.9
N2—C9—C12121.0 (2)C17—C18—H18B109.9
N1—C9—C12119.47 (19)H18A—C18—H18B108.3
C21—O4—C22111.8 (2)H9A—O9—H9B118 (4)
C5—C6—C7119.5 (2)C6—C5—C4121.7 (2)
C5—C6—H6120.2C6—C5—H5119.2
C7—C6—H6120.2C4—C5—H5119.2
C26—O8—H8A115 (3)C2—C1—H1174 (2)
C8—C7—C6119.4 (2)O5—C23—O6123.9 (3)
C8—C7—N1115.84 (19)O5—C23—C24125.0 (3)
C6—C7—N1124.8 (2)O6—C23—C24111.1 (3)
C23—O6—H6A110 (3)O4—C22—H22A109.5
C14—C13—C12120.2 (2)O4—C22—H22B109.5
C14—C13—H13119.9H22A—C22—H22B109.5
C12—C13—H13119.9O4—C22—H22C109.5
O3—C20—C21107.86 (18)H22A—C22—H22C109.5
O3—C20—H20A110.1H22B—C22—H22C109.5
C21—C20—H20A110.1C24—C25—C26115.1 (3)
O3—C20—H20B110.1C24—C25—H25A108.5
C21—C20—H20B110.1C26—C25—H25A108.5
H20A—C20—H20B108.4C24—C25—H25B108.5
O1—C15—C16125.1 (2)C26—C25—H25B108.5
O1—C15—C14114.71 (18)H25A—C25—H25B107.5
C16—C15—C14120.22 (19)C23—C24—C25114.7 (3)
C15—C16—C11119.6 (2)C23—C24—H24A108.6
C15—C16—H16120.2C25—C24—H24A108.6
C11—C16—H16120.2C23—C24—H24B108.6
C8—C3—C4119.6 (2)C25—C24—H24B108.6
C8—C3—C2119.6 (2)H24A—C24—H24B107.6
C4—C3—C2120.8 (2)O2—C19—H19A109.5
C7—C8—C3121.0 (2)O2—C19—H19B109.5
C7—C8—H8119.5H19A—C19—H19B109.5
C3—C8—H8119.5O2—C19—H19C109.5
O1—C17—C18107.41 (19)H19A—C19—H19C109.5
O1—C17—H17A110.2H19B—C19—H19C109.5
(Erlotinib-urea) top
Crystal data top
C23H27N5O5Dx = 1.321 Mg m3
Mr = 453.50Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, PccnCell parameters from 10204 reflections
a = 21.6051 (16) Åθ = 2.3–27.5°
b = 23.7024 (18) ŵ = 0.10 mm1
c = 8.9076 (6) ÅT = 150 K
V = 4561.5 (6) Å3Plate, colorless
Z = 80.24 × 0.16 × 0.08 mm
F(000) = 1920
Data collection top
XtaLABmini
diffractometer
4257 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.118
Graphite monochromatorθmax = 27.5°, θmin = 1.3°
Absorption correction: multi-scan
SADABS
h = 2828
Tmin = 0.799, Tmax = 1.000k = 3030
45968 measured reflectionsl = 1111
5241 independent reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.051Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.169H atoms treated by a mixture of independent and constrained refinement
S = 1.10 w = 1/[σ2(Fo2) + (0.086P)2 + 1.4833P]
where P = (Fo2 + 2Fc2)/3
5241 reflections(Δ/σ)max = 0.001
320 parametersΔρmax = 0.31 e Å3
0 restraintsΔρmin = 0.37 e Å3
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C230.97369 (8)0.55831 (7)0.8333 (2)0.0258 (4)
C20.05151 (10)0.73571 (8)1.0465 (3)0.0375 (5)
H4A0.9208 (12)0.5974 (10)0.695 (3)0.044 (7)*
H5C0.8909 (12)0.5382 (10)0.877 (3)0.041 (6)*
H5B0.9400 (12)0.5097 (11)0.973 (3)0.044 (7)*
H4B0.9885 (14)0.6035 (12)0.664 (3)0.055 (8)*
H20.1166 (12)0.5597 (10)0.862 (3)0.045 (7)*
C150.22620 (8)0.40557 (8)0.5989 (2)0.0284 (4)
H150.25890.38600.55520.034*
C160.16617 (8)0.38958 (7)0.5694 (2)0.0268 (4)
O30.05852 (5)0.39718 (5)0.60995 (15)0.0291 (3)
O10.14779 (6)0.34581 (5)0.48118 (16)0.0320 (3)
O51.02867 (6)0.54857 (5)0.86776 (15)0.0296 (3)
N20.26275 (7)0.54111 (7)0.88582 (19)0.0298 (4)
O20.14998 (7)0.22517 (6)0.47924 (16)0.0368 (3)
O40.06612 (6)0.39654 (6)0.49988 (15)0.0337 (3)
N30.29912 (7)0.46440 (7)0.73139 (19)0.0304 (4)
N10.15812 (7)0.56614 (6)0.89440 (18)0.0285 (3)
N50.92689 (8)0.53351 (8)0.9064 (2)0.0343 (4)
C90.20437 (8)0.53092 (7)0.8471 (2)0.0257 (4)
C110.23853 (8)0.45183 (7)0.6955 (2)0.0265 (4)
C100.30616 (8)0.50676 (8)0.8250 (2)0.0319 (4)
H100.34670.51420.85360.038*
C70.16113 (8)0.61570 (7)0.9835 (2)0.0274 (4)
C210.04990 (8)0.38991 (8)0.6536 (2)0.0286 (4)
H21A0.04220.35040.67520.034*
H21B0.08360.40270.71690.034*
C140.11570 (8)0.41956 (8)0.6362 (2)0.0259 (4)
C130.12697 (8)0.46658 (7)0.7220 (2)0.0259 (4)
H130.09400.48760.75920.031*
C170.19459 (9)0.31212 (8)0.4087 (2)0.0324 (4)
H17A0.22720.30270.47920.039*
H17B0.21270.33270.32550.039*
C120.18837 (8)0.48336 (7)0.75412 (19)0.0248 (4)
C40.15411 (10)0.71341 (9)1.1599 (2)0.0380 (5)
H40.15230.74581.21870.046*
C220.12355 (9)0.36924 (9)0.4670 (2)0.0352 (4)
H22A0.12050.32990.49180.053*
H22B0.13270.37320.36200.053*
H22C0.15600.38630.52500.053*
C30.10622 (9)0.70075 (8)1.0593 (2)0.0316 (4)
C80.11031 (8)0.65226 (8)0.9711 (2)0.0296 (4)
H80.07890.64410.90310.036*
N40.95966 (9)0.59515 (9)0.7233 (2)0.0410 (4)
C180.16341 (9)0.25944 (8)0.3530 (2)0.0329 (4)
H18A0.12550.26900.30040.039*
H18B0.19050.23940.28430.039*
C60.20842 (9)0.62846 (8)1.0842 (2)0.0326 (4)
H60.24240.60471.09370.039*
C200.00730 (8)0.42401 (8)0.6851 (2)0.0298 (4)
H20A0.00210.46220.64840.036*
H20B0.01490.42560.79240.036*
C50.20409 (10)0.67730 (9)1.1706 (2)0.0382 (5)
H50.23580.68581.23740.046*
C190.12146 (11)0.17308 (9)0.4387 (3)0.0487 (6)
H19A0.08570.18040.37790.073*
H19B0.10920.15330.52790.073*
H19C0.15030.15050.38310.073*
C10.00622 (11)0.76373 (9)1.0323 (3)0.0476 (6)
H10.02920.78561.02110.057*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C230.0208 (8)0.0263 (8)0.0302 (9)0.0040 (6)0.0012 (7)0.0028 (7)
C20.0361 (11)0.0268 (9)0.0497 (12)0.0051 (8)0.0077 (9)0.0022 (9)
C150.0205 (8)0.0287 (9)0.0361 (10)0.0045 (7)0.0042 (7)0.0036 (8)
C160.0227 (8)0.0257 (8)0.0320 (9)0.0017 (6)0.0009 (7)0.0014 (7)
O30.0172 (6)0.0324 (7)0.0378 (7)0.0008 (5)0.0006 (5)0.0066 (5)
O10.0234 (7)0.0296 (7)0.0431 (8)0.0041 (5)0.0016 (5)0.0081 (6)
O50.0175 (6)0.0303 (7)0.0409 (7)0.0011 (5)0.0006 (5)0.0027 (5)
N20.0189 (7)0.0292 (8)0.0414 (9)0.0018 (6)0.0002 (6)0.0031 (7)
O20.0427 (8)0.0308 (7)0.0370 (8)0.0066 (6)0.0023 (6)0.0060 (6)
O40.0236 (7)0.0429 (8)0.0346 (7)0.0055 (6)0.0013 (5)0.0042 (6)
N30.0172 (7)0.0310 (8)0.0431 (9)0.0003 (6)0.0031 (6)0.0040 (7)
N10.0186 (7)0.0274 (8)0.0395 (9)0.0002 (6)0.0004 (6)0.0022 (6)
N50.0166 (8)0.0456 (10)0.0409 (9)0.0012 (7)0.0023 (7)0.0100 (8)
C90.0185 (8)0.0261 (8)0.0324 (9)0.0008 (6)0.0026 (6)0.0061 (7)
C110.0190 (8)0.0282 (9)0.0323 (9)0.0003 (6)0.0022 (7)0.0064 (7)
C100.0163 (8)0.0330 (10)0.0463 (11)0.0014 (7)0.0002 (7)0.0036 (8)
C70.0241 (9)0.0259 (8)0.0323 (9)0.0034 (7)0.0044 (7)0.0023 (7)
C210.0205 (8)0.0338 (9)0.0316 (9)0.0013 (7)0.0012 (7)0.0015 (7)
C140.0174 (8)0.0285 (9)0.0317 (9)0.0023 (6)0.0008 (7)0.0038 (7)
C130.0190 (8)0.0283 (9)0.0305 (9)0.0037 (6)0.0019 (7)0.0014 (7)
C170.0262 (9)0.0314 (9)0.0397 (10)0.0064 (7)0.0082 (8)0.0019 (8)
C120.0190 (8)0.0255 (8)0.0300 (9)0.0006 (6)0.0013 (6)0.0051 (7)
C40.0391 (11)0.0324 (10)0.0425 (11)0.0066 (8)0.0035 (9)0.0057 (9)
C220.0234 (9)0.0406 (11)0.0415 (11)0.0016 (8)0.0038 (8)0.0052 (9)
C30.0299 (9)0.0248 (9)0.0400 (10)0.0043 (7)0.0061 (8)0.0021 (8)
C80.0235 (9)0.0289 (9)0.0365 (10)0.0025 (7)0.0019 (7)0.0025 (8)
N40.0304 (10)0.0530 (11)0.0395 (10)0.0081 (8)0.0010 (8)0.0146 (9)
C180.0312 (10)0.0370 (10)0.0306 (9)0.0066 (8)0.0005 (8)0.0045 (8)
C60.0247 (9)0.0356 (10)0.0376 (10)0.0019 (7)0.0007 (7)0.0032 (8)
C200.0196 (8)0.0329 (9)0.0368 (10)0.0020 (7)0.0032 (7)0.0062 (8)
C50.0330 (10)0.0406 (11)0.0409 (11)0.0074 (9)0.0047 (8)0.0036 (9)
C190.0441 (13)0.0322 (11)0.0700 (16)0.0050 (9)0.0033 (11)0.0132 (10)
C10.0350 (11)0.0325 (11)0.0754 (16)0.0012 (9)0.0084 (11)0.0009 (11)
Geometric parameters (Å, º) top
C23—O51.248 (2)C21—C201.503 (2)
C23—N51.339 (2)C21—H21A0.9700
C23—N41.347 (2)C21—H21B0.9700
C2—C11.189 (3)C14—C131.373 (3)
C2—C31.448 (3)C13—C121.414 (2)
C15—C161.377 (2)C13—H130.9300
C15—C111.419 (3)C17—C181.503 (3)
C15—H150.9300C17—H17A0.9700
C16—O11.361 (2)C17—H17B0.9700
C16—C141.431 (2)C4—C51.381 (3)
O3—C141.365 (2)C4—C31.401 (3)
O3—C201.441 (2)C4—H40.9300
O1—C171.441 (2)C22—H22A0.9600
N2—C91.330 (2)C22—H22B0.9600
N2—C101.355 (2)C22—H22C0.9600
O2—C181.417 (2)C3—C81.395 (3)
O2—C191.426 (2)C8—H80.9300
O4—C211.422 (2)N4—H4A0.88 (3)
O4—C221.430 (2)N4—H4B0.84 (3)
N3—C101.314 (3)C18—H18A0.9700
N3—C111.380 (2)C18—H18B0.9700
N1—C91.368 (2)C6—C51.393 (3)
N1—C71.419 (2)C6—H60.9300
N1—H20.96 (3)C20—H20A0.9700
N5—H5C0.83 (3)C20—H20B0.9700
N5—H5B0.86 (3)C5—H50.9300
C9—C121.441 (3)C19—H19A0.9600
C11—C121.416 (2)C19—H19B0.9600
C10—H100.9300C19—H19C0.9600
C7—C61.393 (3)C1—H10.9300
C7—C81.403 (3)
O5—C23—N5121.19 (17)O1—C17—H17B110.3
O5—C23—N4120.85 (17)C18—C17—H17B110.3
N5—C23—N4117.94 (17)H17A—C17—H17B108.6
C1—C2—C3178.2 (3)C13—C12—C11119.65 (16)
C16—C15—C11120.35 (16)C13—C12—C9124.14 (16)
C16—C15—H15119.8C11—C12—C9116.19 (15)
C11—C15—H15119.8C5—C4—C3119.26 (19)
O1—C16—C15126.51 (16)C5—C4—H4120.4
O1—C16—C14113.35 (15)C3—C4—H4120.4
C15—C16—C14120.13 (17)O4—C22—H22A109.5
C14—O3—C20116.36 (14)O4—C22—H22B109.5
C16—O1—C17118.46 (14)H22A—C22—H22B109.5
C9—N2—C10116.35 (16)O4—C22—H22C109.5
C18—O2—C19112.58 (17)H22A—C22—H22C109.5
C21—O4—C22111.19 (14)H22B—C22—H22C109.5
C10—N3—C11114.97 (15)C8—C3—C4119.33 (18)
C9—N1—C7130.05 (16)C8—C3—C2118.59 (18)
C9—N1—H2119.6 (15)C4—C3—C2122.05 (18)
C7—N1—H2110.3 (15)C3—C8—C7120.93 (18)
C23—N5—H5C119.6 (17)C3—C8—H8119.5
C23—N5—H5B111.8 (17)C7—C8—H8119.5
H5C—N5—H5B128 (2)C23—N4—H4A117.7 (16)
N2—C9—N1120.14 (17)C23—N4—H4B116.3 (19)
N2—C9—C12121.23 (16)H4A—N4—H4B121 (2)
N1—C9—C12118.62 (15)O2—C18—C17107.84 (15)
N3—C11—C12121.75 (17)O2—C18—H18A110.1
N3—C11—C15119.05 (16)C17—C18—H18A110.1
C12—C11—C15119.19 (16)O2—C18—H18B110.1
N3—C10—N2129.24 (17)C17—C18—H18B110.1
N3—C10—H10115.4H18A—C18—H18B108.5
N2—C10—H10115.4C5—C6—C7119.13 (18)
C6—C7—C8119.37 (17)C5—C6—H6120.4
C6—C7—N1124.99 (17)C7—C6—H6120.4
C8—C7—N1115.56 (16)O3—C20—C21107.88 (15)
O4—C21—C20108.87 (15)O3—C20—H20A110.1
O4—C21—H21A109.9C21—C20—H20A110.1
C20—C21—H21A109.9O3—C20—H20B110.1
O4—C21—H21B109.9C21—C20—H20B110.1
C20—C21—H21B109.9H20A—C20—H20B108.4
H21A—C21—H21B108.3C4—C5—C6121.97 (19)
O3—C14—C13124.84 (15)C4—C5—H5119.0
O3—C14—C16115.19 (16)C6—C5—H5119.0
C13—C14—C16119.96 (16)O2—C19—H19A109.5
C14—C13—C12120.48 (16)O2—C19—H19B109.5
C14—C13—H13119.8H19A—C19—H19B109.5
C12—C13—H13119.8O2—C19—H19C109.5
O1—C17—C18107.08 (15)H19A—C19—H19C109.5
O1—C17—H17A110.3H19B—C19—H19C109.5
C18—C17—H17A110.3C2—C1—H1180.0
 

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