Erlotinib hydro-chloride: an anti-cancer agent.

In the cation of the title compound, C(22)H(24)N(3)O(4) (+)·Cl(-), an active ingredient of the anti-cancer drug also known as Tarceva, the quinazoline ring system is planar within 0.044 (3) Å. The dihedral angle formed by the mean planes of the two six-membered quinazoline rings is 3.2 (1)°. Both N-bound H atoms participate in N-H⋯Cl bonds, which link the ions into infinite chains running along the b axis. C-H⋯O inter-actions involving neighboring cations provide additional stabilization of these aggregates.

Related literature

For related literature, see: Herbst et al. (2005 ▶); Minna & Dowell (2005 ▶); Li et al. (2007 ▶); Xia (2005 ▶). For bond-length data, see: Allen et al. (1987 ▶).

Experimental

Crystal data

C22H24N3O4 +·Cl−

M = 429.89

Monoclinic,

a = 14.5351 (15) Å

b = 18.4863 (19) Å

c = 8.1222 (8) Å

β = 102.966 (2)°

V = 2126.8 (4) Å3

Z = 4

Mo Kα radiation

μ = 0.21 mm−1

T = 293 (2) K

0.26 × 0.22 × 0.20 mm

Data collection

Bruker APEX area-detector diffractometer

Absorption correction: none

24377 measured reflections

5001 independent reflections

3649 reflections with I > 2σ(I)

R int = 0.050

Refinement

R[F 2 > 2σ(F 2)] = 0.073

wR(F 2) = 0.151

S = 1.16

5001 reflections

275 parameters

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.33 e Å−3

Δρmin = −0.25 e Å−3

Data collection: SMART (Bruker, 2001 ▶); cell refinement: SAINT (Bruker, 2001 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶) and PLATON (Spek, 2003 ▶); software used to prepare material for publication: SHELXL97 and PARST (Nardelli, 1995 ▶).

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808011707/ya2075sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808011707/ya2075Isup2.hkl

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

C22H24N3O4+·Cl–	F000 = 904
Mr = 429.89	Dx = 1.343 Mg m−3
Monoclinic, P21/c	Mo Kα radiation λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 9448 reflections
a = 14.5351 (15) Å	θ = 2.2–23.4º
b = 18.4863 (19) Å	µ = 0.21 mm−1
c = 8.1222 (8) Å	T = 293 (2) K
β = 102.966 (2)º	Block, colourless
V = 2126.8 (4) Å3	0.26 × 0.22 × 0.20 mm
Z = 4

Bruker APEX area-detector diffractometer	3649 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.050
Monochromator: graphite	θmax = 28.0º
T = 293(2) K	θmin = 1.8º
ω scans	h = −18→19
Absorption correction: none	k = −24→24
24377 measured reflections	l = −10→10
5001 independent reflections

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.073	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.151	w = 1/[σ2(Fo2) + (0.0551P)2 + 0.7563P] where P = (Fo2 + 2Fc2)/3
S = 1.16	(Δ/σ)max = 0.001
5001 reflections	Δρmax = 0.33 e Å−3
275 parameters	Δρmin = −0.25 e Å−3
Primary atom site location: structure-invariant direct methods	Extinction correction: none

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

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

	x	y	z	Uiso*/Ueq
Cl1	0.50200 (5)	0.34427 (3)	0.62635 (9)	0.0469 (2)
O1	0.27725 (11)	0.61695 (9)	0.9544 (2)	0.0395 (4)
O2	0.10485 (14)	0.70220 (13)	0.9170 (3)	0.0648 (6)
O3	0.29876 (12)	0.48732 (9)	0.8521 (2)	0.0417 (4)
O4	0.20059 (13)	0.31485 (10)	0.6875 (3)	0.0514 (5)
N1	0.57019 (14)	0.69146 (10)	0.8273 (3)	0.0395 (5)
HN1	0.5603	0.7355	0.8527	0.047*
N2	0.67238 (14)	0.60941 (11)	0.7423 (3)	0.0408 (5)
N3	0.63506 (13)	0.48880 (10)	0.7058 (3)	0.0350 (5)
H3	0.5945	0.4550	0.7065	0.042*
C1	0.64787 (18)	0.67467 (13)	0.7780 (4)	0.0435 (7)
H1	0.6887	0.7123	0.7678	0.052*
C2	0.61060 (16)	0.55508 (12)	0.7464 (3)	0.0318 (5)
C3	0.52182 (16)	0.56803 (12)	0.7918 (3)	0.0310 (5)
C4	0.45169 (16)	0.51536 (12)	0.7961 (3)	0.0321 (5)
H4	0.4604	0.4681	0.7637	0.039*
C5	0.37123 (16)	0.53333 (13)	0.8474 (3)	0.0324 (5)
C6	0.35795 (16)	0.60529 (13)	0.9019 (3)	0.0326 (5)
C7	0.42426 (17)	0.65734 (12)	0.8963 (3)	0.0346 (5)
H7	0.4158	0.7044	0.9305	0.042*
C8	0.50471 (16)	0.63882 (12)	0.8385 (3)	0.0320 (5)
C9	0.26703 (18)	0.68616 (14)	1.0300 (4)	0.0417 (6)
H9A	0.2742	0.7248	0.9530	0.050*
H9B	0.3151	0.6919	1.1333	0.050*
C10	0.17127 (19)	0.68926 (15)	1.0675 (4)	0.0448 (6)
H10A	0.1574	0.6439	1.1166	0.054*
H10B	0.1689	0.7277	1.1478	0.054*
C11	0.0123 (3)	0.7093 (3)	0.9450 (7)	0.1109 (16)
H11A	−0.0314	0.7178	0.8392	0.166*
H11B	0.0106	0.7492	1.0197	0.166*
H11C	−0.0047	0.6656	0.9949	0.166*
C12	0.30023 (17)	0.41876 (13)	0.7695 (4)	0.0422 (6)
H12A	0.3512	0.3889	0.8318	0.051*
H12B	0.3093	0.4256	0.6558	0.051*
C13	0.2062 (2)	0.38355 (15)	0.7650 (4)	0.0510 (7)
H13A	0.1974	0.3784	0.8793	0.061*
H13B	0.1560	0.4142	0.7029	0.061*
C14	0.1801 (3)	0.3188 (2)	0.5094 (5)	0.0765 (11)
H14A	0.1774	0.2709	0.4631	0.115*
H14B	0.2286	0.3460	0.4740	0.115*
H14C	0.1203	0.3423	0.4699	0.115*
C15	0.72087 (16)	0.46773 (12)	0.6616 (3)	0.0327 (5)
C16	0.71529 (18)	0.41268 (14)	0.5436 (3)	0.0396 (6)
H16	0.6575	0.3912	0.4968	0.048*
C17	0.7960 (2)	0.38986 (16)	0.4959 (4)	0.0474 (7)
H17	0.7922	0.3529	0.4169	0.057*
C18	0.88191 (19)	0.42120 (15)	0.5641 (4)	0.0473 (7)
H18	0.9356	0.4060	0.5296	0.057*
C19	0.88874 (17)	0.47541 (13)	0.6842 (3)	0.0395 (6)
C20	0.80763 (17)	0.49842 (13)	0.7347 (3)	0.0371 (6)
H20	0.8118	0.5341	0.8168	0.045*
C21	0.9793 (2)	0.50773 (16)	0.7563 (4)	0.0490 (7)
C22	1.0541 (2)	0.5325 (2)	0.8100 (5)	0.0653 (9)
H22	1.115 (2)	0.5534 (16)	0.849 (4)	0.063 (9)*

	U11	U22	U33	U12	U13	U23
Cl1	0.0508 (4)	0.0276 (3)	0.0642 (5)	−0.0062 (3)	0.0173 (3)	−0.0023 (3)
O1	0.0339 (9)	0.0328 (9)	0.0559 (11)	−0.0003 (7)	0.0190 (8)	−0.0044 (8)
O2	0.0438 (12)	0.0814 (16)	0.0696 (15)	0.0176 (11)	0.0135 (10)	0.0081 (12)
O3	0.0353 (9)	0.0315 (9)	0.0628 (12)	−0.0071 (7)	0.0207 (9)	−0.0071 (8)
O4	0.0525 (12)	0.0327 (10)	0.0694 (14)	−0.0093 (9)	0.0145 (10)	−0.0046 (9)
N1	0.0373 (12)	0.0223 (10)	0.0611 (14)	−0.0008 (9)	0.0158 (10)	−0.0023 (10)
N2	0.0325 (11)	0.0270 (11)	0.0661 (15)	−0.0004 (9)	0.0181 (10)	0.0036 (10)
N3	0.0276 (10)	0.0264 (10)	0.0527 (13)	−0.0003 (8)	0.0127 (9)	0.0009 (9)
C1	0.0330 (14)	0.0291 (13)	0.0715 (19)	−0.0040 (11)	0.0184 (13)	0.0048 (12)
C2	0.0279 (12)	0.0266 (12)	0.0412 (14)	0.0007 (9)	0.0083 (10)	0.0030 (10)
C3	0.0280 (12)	0.0289 (12)	0.0361 (13)	0.0010 (9)	0.0073 (10)	0.0027 (10)
C4	0.0311 (12)	0.0232 (11)	0.0424 (14)	0.0007 (9)	0.0091 (10)	0.0008 (10)
C5	0.0299 (12)	0.0299 (12)	0.0377 (13)	−0.0032 (10)	0.0080 (10)	0.0028 (10)
C6	0.0297 (12)	0.0329 (13)	0.0361 (13)	0.0023 (10)	0.0095 (10)	0.0009 (10)
C7	0.0361 (13)	0.0237 (11)	0.0447 (14)	0.0023 (10)	0.0107 (11)	−0.0030 (10)
C8	0.0299 (12)	0.0263 (12)	0.0394 (13)	−0.0007 (9)	0.0068 (10)	0.0027 (10)
C9	0.0431 (15)	0.0349 (14)	0.0490 (16)	0.0055 (12)	0.0147 (12)	−0.0035 (12)
C10	0.0493 (16)	0.0390 (15)	0.0512 (16)	0.0085 (12)	0.0221 (13)	0.0014 (13)
C11	0.045 (2)	0.152 (4)	0.135 (4)	0.034 (2)	0.019 (2)	−0.013 (4)
C12	0.0350 (14)	0.0305 (13)	0.0636 (18)	−0.0034 (11)	0.0162 (12)	−0.0027 (12)
C13	0.0448 (16)	0.0404 (15)	0.073 (2)	−0.0095 (12)	0.0240 (15)	−0.0085 (14)
C14	0.093 (3)	0.066 (2)	0.077 (3)	−0.032 (2)	0.031 (2)	−0.0167 (19)
C15	0.0338 (13)	0.0260 (12)	0.0403 (14)	0.0051 (10)	0.0125 (11)	0.0077 (10)
C16	0.0385 (14)	0.0353 (14)	0.0443 (15)	0.0027 (11)	0.0079 (11)	0.0015 (11)
C17	0.0542 (17)	0.0441 (16)	0.0466 (16)	0.0070 (13)	0.0167 (13)	−0.0070 (13)
C18	0.0421 (16)	0.0517 (17)	0.0538 (17)	0.0127 (13)	0.0230 (13)	0.0022 (14)
C19	0.0330 (13)	0.0352 (14)	0.0533 (17)	0.0038 (11)	0.0158 (12)	0.0107 (12)
C20	0.0346 (13)	0.0285 (12)	0.0496 (16)	0.0018 (10)	0.0123 (11)	−0.0001 (11)
C21	0.0387 (16)	0.0495 (17)	0.064 (2)	0.0052 (13)	0.0237 (14)	0.0062 (14)
C22	0.0416 (19)	0.077 (2)	0.082 (2)	−0.0098 (17)	0.0233 (17)	−0.0084 (19)

O1—C6	1.352 (3)	C9—H9B	0.9700
O1—C9	1.441 (3)	C10—H10A	0.9700
O2—C10	1.397 (3)	C10—H10B	0.9700
O2—C11	1.419 (4)	C11—H11A	0.9600
O3—C5	1.361 (3)	C11—H11B	0.9600
O3—C12	1.436 (3)	C11—H11C	0.9600
O4—C13	1.412 (3)	C12—C13	1.507 (3)
O4—C14	1.412 (4)	C12—H12A	0.9700
N1—C1	1.317 (3)	C12—H12B	0.9700
N1—C8	1.378 (3)	C13—H13A	0.9700
N1—HN1	0.8600	C13—H13B	0.9700
N2—C1	1.309 (3)	C14—H14A	0.9600
N2—C2	1.353 (3)	C14—H14B	0.9600
N3—C2	1.337 (3)	C14—H14C	0.9600
N3—C15	1.427 (3)	C15—C16	1.388 (3)
N3—H3	0.8600	C15—C20	1.389 (3)
C1—H1	0.9300	C16—C17	1.382 (4)
C2—C3	1.440 (3)	C16—H16	0.9300
C3—C8	1.400 (3)	C17—C18	1.375 (4)
C3—C4	1.416 (3)	C17—H17	0.9300
C4—C5	1.368 (3)	C18—C19	1.386 (4)
C4—H4	0.9300	C18—H18	0.9300
C5—C6	1.429 (3)	C19—C20	1.399 (3)
C6—C7	1.370 (3)	C19—C21	1.444 (4)
C7—C8	1.397 (3)	C20—H20	0.9300
C7—H7	0.9300	C21—C22	1.170 (4)
C9—C10	1.491 (3)	C22—H22	0.95 (3)
C9—H9A	0.9700
C6—O1—C9	117.09 (19)	H10A—C10—H10B	108.3
C10—O2—C11	111.7 (3)	O2—C11—H11A	109.5
C5—O3—C12	116.48 (18)	O2—C11—H11B	109.5
C13—O4—C14	112.8 (2)	H11A—C11—H11B	109.5
C1—N1—C8	120.4 (2)	O2—C11—H11C	109.5
C1—N1—HN1	119.8	H11A—C11—H11C	109.5
C8—N1—HN1	119.8	H11B—C11—H11C	109.5
C1—N2—C2	117.6 (2)	O3—C12—C13	106.5 (2)
C2—N3—C15	127.4 (2)	O3—C12—H12A	110.4
C2—N3—H3	116.3	C13—C12—H12A	110.4
C15—N3—H3	116.3	O3—C12—H12B	110.4
N2—C1—N1	125.4 (2)	C13—C12—H12B	110.4
N2—C1—H1	117.3	H12A—C12—H12B	108.6
N1—C1—H1	117.3	O4—C13—C12	111.1 (2)
N3—C2—N2	117.4 (2)	O4—C13—H13A	109.4
N3—C2—C3	121.2 (2)	C12—C13—H13A	109.4
N2—C2—C3	121.4 (2)	O4—C13—H13B	109.4
C8—C3—C4	117.6 (2)	C12—C13—H13B	109.4
C8—C3—C2	116.7 (2)	H13A—C13—H13B	108.0
C4—C3—C2	125.7 (2)	O4—C14—H14A	109.5
C5—C4—C3	120.7 (2)	O4—C14—H14B	109.5
C5—C4—H4	119.7	H14A—C14—H14B	109.5
C3—C4—H4	119.7	O4—C14—H14C	109.5
O3—C5—C4	125.2 (2)	H14A—C14—H14C	109.5
O3—C5—C6	114.5 (2)	H14B—C14—H14C	109.5
C4—C5—C6	120.3 (2)	C16—C15—C20	120.1 (2)
O1—C6—C7	124.4 (2)	C16—C15—N3	117.1 (2)
O1—C6—C5	115.7 (2)	C20—C15—N3	122.8 (2)
C7—C6—C5	119.9 (2)	C17—C16—C15	119.7 (2)
C6—C7—C8	119.2 (2)	C17—C16—H16	120.1
C6—C7—H7	120.4	C15—C16—H16	120.1
C8—C7—H7	120.4	C18—C17—C16	120.6 (3)
N1—C8—C7	119.4 (2)	C18—C17—H17	119.7
N1—C8—C3	118.3 (2)	C16—C17—H17	119.7
C7—C8—C3	122.2 (2)	C17—C18—C19	120.2 (2)
O1—C9—C10	108.1 (2)	C17—C18—H18	119.9
O1—C9—H9A	110.1	C19—C18—H18	119.9
C10—C9—H9A	110.1	C18—C19—C20	119.6 (2)
O1—C9—H9B	110.1	C18—C19—C21	120.0 (2)
C10—C9—H9B	110.1	C20—C19—C21	120.4 (2)
H9A—C9—H9B	108.4	C15—C20—C19	119.6 (2)
O2—C10—C9	108.7 (2)	C15—C20—H20	120.2
O2—C10—H10A	109.9	C19—C20—H20	120.2
C9—C10—H10A	109.9	C22—C21—C19	177.3 (3)
O2—C10—H10B	109.9	C21—C22—H22	178 (2)
C9—C10—H10B	109.9
C2—N2—C1—N1	4.2 (4)	C1—N1—C8—C3	−1.7 (4)
C8—N1—C1—N2	−2.7 (4)	C6—C7—C8—N1	177.9 (2)
C15—N3—C2—N2	1.5 (4)	C6—C7—C8—C3	−2.4 (4)
C15—N3—C2—C3	−178.7 (2)	C4—C3—C8—N1	−177.0 (2)
C1—N2—C2—N3	178.4 (2)	C2—C3—C8—N1	4.1 (3)
C1—N2—C2—C3	−1.3 (4)	C4—C3—C8—C7	3.4 (4)
N3—C2—C3—C8	177.5 (2)	C2—C3—C8—C7	−175.5 (2)
N2—C2—C3—C8	−2.7 (3)	C6—O1—C9—C10	176.3 (2)
N3—C2—C3—C4	−1.2 (4)	C11—O2—C10—C9	−177.2 (3)
N2—C2—C3—C4	178.5 (2)	O1—C9—C10—O2	−76.9 (3)
C8—C3—C4—C5	−1.2 (3)	C5—O3—C12—C13	−170.3 (2)
C2—C3—C4—C5	177.5 (2)	C14—O4—C13—C12	−79.6 (3)
C12—O3—C5—C4	−11.3 (3)	O3—C12—C13—O4	−179.3 (2)
C12—O3—C5—C6	168.7 (2)	C2—N3—C15—C16	−146.2 (2)
C3—C4—C5—O3	178.3 (2)	C2—N3—C15—C20	35.6 (4)
C3—C4—C5—C6	−1.7 (4)	C20—C15—C16—C17	−1.7 (4)
C9—O1—C6—C7	−8.6 (3)	N3—C15—C16—C17	−179.9 (2)
C9—O1—C6—C5	172.4 (2)	C15—C16—C17—C18	−0.1 (4)
O3—C5—C6—O1	1.8 (3)	C16—C17—C18—C19	1.1 (4)
C4—C5—C6—O1	−178.3 (2)	C17—C18—C19—C20	−0.5 (4)
O3—C5—C6—C7	−177.3 (2)	C17—C18—C19—C21	179.5 (3)
C4—C5—C6—C7	2.7 (4)	C16—C15—C20—C19	2.4 (4)
O1—C6—C7—C8	−179.6 (2)	N3—C15—C20—C19	−179.6 (2)
C5—C6—C7—C8	−0.6 (4)	C18—C19—C20—C15	−1.3 (4)
C1—N1—C8—C7	177.9 (2)	C21—C19—C20—C15	178.7 (2)

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3···Cl1	0.86	2.46	3.277 (2)	160
N1—HN1···Cl1i	0.86	2.23	3.066 (2)	165
C1—H1···O4i	0.93	2.46	3.372 (3)	167

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N3—H3⋯Cl1	0.86	2.46	3.277 (2)	160
N1—HN1⋯Cl1i	0.86	2.23	3.066 (2)	165
C1—H1⋯O4i	0.93	2.46	3.372 (3)	167

Symmetry code: (i) .