Erlotinib hydro­chloride: an anti­cancer agent

S Selvanayagam; B Sridhar; K Ravikumar

doi:10.1107/S1600536808011707

. 2008 Apr 30;64(Pt 5):o931. doi: 10.1107/S1600536808011707

Erlotinib hydrochloride: an anticancer agent

S Selvanayagam ^a,^*, B Sridhar ^b, K Ravikumar ^b

PMCID: PMC2961266 PMID: 21202412

Abstract

In the cation of the title compound, C₂₂H₂₄N₃O₄ ⁺·Cl⁻, an active ingredient of the anticancer 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 interactions 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 _r = 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
Δρ_max = 0.33 e Å⁻³
Δρ_min = −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 ▶).

Supplementary Material

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

e-64-0o931-sup1.cif^{(21.6KB, cif)}

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

e-64-0o931-Isup2.hkl^{(240KB, hkl)}

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

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

Open in a new tab

Symmetry code: (i) Inline graphic .

Acknowledgments

SS thanks the Vice Chancellor and the management of Kalasalingam University, Anand Nagar, Krishnankoil, for their support and encouragement.

supplementary crystallographic information

Comment

Erlotinib hydrochloride, (I), also known under its tradename Tarceva, is a potent reversible epidermal growth factor receptor tyrosine kinase inhibitor with single agent activity in patients with non-small lung cancer, pancreatic cancer and several other types of cancer (Herbst et al., 2005). It is the first drug to demonstrate an increase in survival in phase III trials in patients with advanced non-small cell lung cancer (Minna & Dowell, 2005). It has recently been shown to be potent inhibitor of JAK2 V617F activity; JAK2 V617F is a mutant of tyrosine kinase JAK2 (Li et al., 2007). As no crystal structure of the title compound has yet been published, we have undertaken the single-crystal X-ray diffraction study and report here its results.

The X-ray study confirmed the molecular structure and atomic connectivity for (I), as illustrated in Fig. 1. The C21—C22 bond length [1.170 (4) Å] is consistent with its acetylenic character, as evidenced by literature value of 1.174 (11) Å (see Allen et al., 1987). The geometry of the quinazoline ring system is comparable to that in the reported related structure (Xia, 2005).

The bicyclic system is effectively planar with a maximum deviation of 0.044 (3) Å for the C1 atom. The dihedral angle formed by the mean planes of two six membered rings of quinazoline moiety is 3.2 (1)°. The benzene ring C15—C20 and its attached ethynyl group are coplanar with a maximum deviation -0.011 (3) Å for the C20 atom. The dihedral angle between this ring and quinazoline ring system is 34.4 (1)°. The short contacts H3···H4 (2.12 Å) and H7···H9A (2.14 Å) result in substantial widening of the C2—N3—C15 and C6—O1—C9 bond angles [127.4 (2)° and 117.1 (2)°, respectively].

Both N-bound H atoms (HN1 and H3) participate in H-bonds with the Cl1 anion (Table 2). These bonds link cations and anions into the infinite chains running along the b axis of the crystal. The C1—H1···O4 interactions involving neighboring cations provide additional stabilization for these chains (Fig. 2).

Experimental

In order to obtain crystals suitable for X-ray study, commercially available erlotinib hydrochloride was dissolved in a methanol-water solution (90:10v/v); the solvents were then allowed to evaporate slowly.