N-[3-Chloro-4-(3-fluoro­benz­yloxy)phen­yl]-6-iodo­quinazolin-4-amine

Zhi-Qiang Cai; Jing-Guo Liu; Wei-Wei Zhou; Yi-Liang Li

doi:10.1107/S1600536810021847

. 2010 Jun 26;66(Pt 7):o1810. doi: 10.1107/S1600536810021847

N-[3-Chloro-4-(3-fluorobenzyloxy)phenyl]-6-iodoquinazolin-4-amine

Zhi-Qiang Cai ^a, Jing-Guo Liu ^a,^b, Wei-Wei Zhou ^a,^b, Yi-Liang Li ^a,^*

PMCID: PMC3006786 PMID: 21588019

Abstract

In the title molecule, C₂₁H₁₄ClFIN₃O, the bicyclic ring system has a twisted conformation; the two fused rings form a dihedral angle of 4.5 (1)°. The dihedral angles between the fused ring system and the benzene rings are 27.3 (6) and 5.3 (5)° while the dihedral angle between the benzene rings is 22.0 (5)°. In the crystal structure, weak intermolecular N—H⋯N hydrogen bonds link the molecules into chains propagating in [100]. A short intermolecular distance of 3.806 (3) Å between the centroids of the fluorobenzene and iodobenzene rings suggests the existence of π–π stacking interactions.

Related literature

For a related structure, see: Calestani et al. (2001 ▶). The title compound is an important intermediate in the synthesis of the anticancer agent lapatinib, see: Kimberly et al. (2006 ▶).

Experimental

Crystal data

C₂₁H₁₄ClFIN₃O
M _r = 505.70
Orthorhombic,
a = 13.128 (3) Å
b = 7.6293 (15) Å
c = 18.898 (4) Å
V = 1892.8 (7) Å³
Z = 4
Mo Kα radiation
μ = 1.86 mm⁻¹
T = 113 K
0.20 × 0.18 × 0.06 mm

Data collection

Rigaku Saturn CCD area-detector diffractometer
Absorption correction: multi-scan (ABSCOR; Higashi, 1995 ▶) T _min = 0.707, T _max = 0.897
11905 measured reflections
3183 independent reflections
2510 reflections with I > 2σ(I)
R _int = 0.045

Refinement

R[F ² > 2σ(F ²)] = 0.030
wR(F ²) = 0.067
S = 1.01
3183 reflections
258 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 1.24 e Å⁻³
Δρ_min = −0.70 e Å⁻³
Absolute structure: Flack (1983 ▶), 1433 Friedel pairs
Flack parameter: −0.039 (19)

Data collection: RAPID-AUTO (Rigaku, 1998 ▶); cell refinement: RAPID-AUTO; data reduction: CrystalStructure (Rigaku/MSC, 2002 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810021847/cv2724sup1.cif

e-66-o1810-sup1.cif^{(21.1KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810021847/cv2724Isup2.hkl

e-66-o1810-Isup2.hkl^{(156.2KB, 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
N1—H21⋯N3ⁱ	0.81 (6)	2.39 (6)	3.128 (6)	151 (6)

Open in a new tab

Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank the State Key Laboratory of Elemento-organic Chemistry, Nankai University, for the X-ray data collection.

supplementary crystallographic information

Comment

The title compound (I) is an important intermediate in the preparation of anticancer agent lapatinib (Kimberly et al., 2006). Herein, the synthesis and the crystal structure of (I) are reported.

In (I) (Fig. 1), all bond lengths and angles are normal and comparable with those observed in the related compound (Calestani et al., 2001). The bicycle quinazoline system has a twisted conformation - two fused rings form a dihedral angle of 4.5 (1)°. In the crystal structure, weak intermolecular N—H···N hydrogen bonds (Table 1) link molecules into chains propagated in direction [100]. Short intermolecular distance of 3.806 (3) Å between the centroids of aromatic rings suggests an existence of π-π interactions.

Experimental

2-Chloro-4-(6-iodo-quinazolin-4-ylamino)-phenol (10 mmol) in acetone (5 ml) was added to a stirred mixture of anhydrous potassium carbonate (20 mmol) and 1-Chloromethyl-3-fluoro-benzene (10 mmol) in dry acetone (25 ml). It was stirred at room temperature for 6 h. Upon completion reaction mixture was diluted with water, extracted with dichloromethane and concentrated. Recrystallization from ethyl acetate afforded title compound in 89% yield as yellow crystal: 1H NMR (DMSO-d6): 9.82 (1H, s, NH), 8.94(1H, s, ArH), 8.60(1H, s, ArH), 8.08(1H, dd, ArH), 8.01(1H, d ArH), 7.72 (1H, dd ArH), 7.49(1H, d ArH), 7.43 (1H, dd ArH), 7.19 (3H, m ArH), 7.14 (1H, t ArH), 5.24(2H, s CH2).