Methyl 1-(7-acetamido-5,8-dimeth­oxy­quinolin-2-yl)-4-methyl-β-carboline-3-carboxyl­ate

Felix Nissen; Dieter Schollmeyer; Heiner Detert

doi:10.1107/S1600536811018794

. 2011 May 25;67(Pt 6):o1497–o1498. doi: 10.1107/S1600536811018794

Methyl 1-(7-acetamido-5,8-dimethoxyquinolin-2-yl)-4-methyl-β-carboline-3-carboxylate

Felix Nissen ^a, Dieter Schollmeyer ^a, Heiner Detert ^a,^*

PMCID: PMC3120419 PMID: 21754865

Abstract

The title compound, C₂₇H₂₄N₄O₅, is an intermediate in the synthesis of lavendamycin via a ruthenium-catalysed [2 + 2 + 2] cycloaddition. An intramolecular hydrogen-bond bridge from the carboline to the quinoline stabilizes a highly planar geometry [maximum deviation = 0.065 (6) Å] for the two rigid units. This hydrogen-bond-stabilized coplanarity has a very close analogy in the structure of the antitumor antibiotic streptonigrin in the solid state and in solution. Intermolecular hydrogen-bond bridges of amides groups along the a axis and π–π stacking interactions [centroid–centroid distance = 3.665 (9) Å] connect molecules arranged in a parallel manner.

Related literature

For metal-catalysed transformations of tethered alkynyl-ynamides to carbolines and other heteroannulated indoles, see: Nissen et al. (2011 ▶); Dassonneville et al. (2010 ▶, 2011 ▶). For the synthesis of the natural product lavendamycin (systematic name 1-(7-amino-5,8-dioxoquinolin-2-yl)-4-methyl-9H-pyrido[3,4-b]indole-3-carboxylic acid) via [2 + 2 + 2] cycloaddition, see: Nissen & Detert (2011 ▶). For the isololation of lavendamycin from streptomyces lavendulae, see: Doyle et al. (1981 ▶). For the anti-tumor activity of lavendamycin, see: Fang et al. (2003 ▶). For the preparation of lavandamycin, see: Behforouz et al. (1996 ▶) Godard et al. (1993 ▶). For related structures, see: Chiu & Lipscomb (1975 ▶); Harding et al. (1993 ▶).

Experimental

Crystal data

C₂₇H₂₄N₄O₅
M _r = 484.50
Triclinic,
a = 4.646 (10) Å
b = 13.81 (3) Å
c = 18.768 (19) Å
α = 102.06 (9)°
β = 95.23 (10)°
γ = 96.85 (11)°
V = 1161 (4) Å³
Z = 2
Cu Kα radiation
μ = 0.80 mm⁻¹
T = 193 K
0.58 × 0.06 × 0.03 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
4993 measured reflections
4412 independent reflections
2069 reflections with I > 2σ(I)
R _int = 0.054
3 standard reflections every 60 min intensity decay: 2%

Refinement

R[F ² > 2σ(F ²)] = 0.083
wR(F ²) = 0.248
S = 0.99
4412 reflections
330 parameters
H-atom parameters constrained
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.34 e Å⁻³

Data collection: CAD-4 Software (Enraf–Nonius, 1989 ▶); cell refinement: CAD-4 Software; data reduction: CORINC (Dräger & Gattow, 1971 ▶); program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2009 ▶); software used to prepare material for publication: PLATON.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811018794/bt5551sup1.cif

e-67-o1497-sup1.cif^{(23.6KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811018794/bt5551Isup2.hkl

e-67-o1497-Isup2.hkl^{(216.1KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811018794/bt5551Isup3.cml

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
N2—H2⋯N3	0.88	2.17	2.693 (7)	118
N4—H4⋯O5ⁱ	0.88	1.98	2.824 (8)	160

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Symmetry code: (i) Inline graphic .

supplementary crystallographic information

Comment

The title compound was prepared as part of a larger project focusing on the synthesis of indolo-annulated heterocycles via [2 + 2+2] cycloaddition of alkynyl-ynamides and nitriles or heterocumulenes catalyzed by rhodium or ruthenium (Nissen et al., 2011; Dassonneville et al., 2011) and is a synthetic precursor of the natural product lavendamycin (Nissen & Detert, 2011). The molecule is built up by two rigid and planar units, both are coplanar. This flat structure is stabilized by an intramolecular hydrogen bond from the carboline-NH to the quinoline-N N2—H2···N3 with a distance of 2.17 Å. Whereas the ester group is coplanar with the carboline core [torsion angle O1—C1—C3—C9 of -0.4 (8)°], the acetamido group is twisted out of the plane of the quinoline framework. The torsion angle C20—N4—C19—C22 amounts to -47.9 (7)°. This torsion can result from the sterical hindrance due to the neighbouring methoxy group, but its ability to act as a hydrogen bridge donor and acceptor is important for the formation of crystals of the title compound. Parallel molecules, arranged in the shape of tilted staples are connected to infinite chains via H-bridging along the a-axis. The tilt angle of the mean plane of the molecules relative to the ab-plane is 54.3°. The second interaction is π-π-stacking, resulting in a distance of only 3.665 (9) Å of the centroids of the pyrrole ring (N2—C6) and the benzo-ring (C6—C14) (symmetry code 1+X,Y,Z). Two molecules, connected via a center of inversion fill the unit cell.

Experimental

Pd/C (10%, 47 mg, 44 µmol, 5 mol%) was added to a suspension of Methyl 1-(5,8-dimethoxy-7-nitroquinolin-2-yl)-4-methyl-β-carboline-3-carboxylate (405 mg, 0.86 mmol) (Nissen & Detert, 2011) in THF (170 ml) and the mixture was stirred 13 h under H₂ atmosphere. Ac₂O (5.0 ml) was added and the mixture was heated to 323 K. After 3 h the solvent was removed in vacuo, the residue dissolved in CH₂Cl₂ and filtered through celite. The filtrate was washed with aqueous NaHCO₃ (8%, 8 ml), dried (MgSO₄) and concentrated. Crystallization from chloroform/diethyl ether yielded the title compound (399 mg, 0.82 mmol, 96%) as a bright yellow solid. M.p. 467–468 K R_f: 0.12 (SiO₂, hexane:ethyl acetate:ethanol 6:3:1).