1-tert-Butyl 2-ethyl 5-bromo-3-(thio­phen-2-ylcarbon­yl)-1H-indole-1,2-dicarboxyl­ate

Mohammad Hassam; Vincent J Smith

doi:10.1107/S1600536813000809

. 2013 Jan 16;69(Pt 2):o237. doi: 10.1107/S1600536813000809

1-tert-Butyl 2-ethyl 5-bromo-3-(thiophen-2-ylcarbonyl)-1H-indole-1,2-dicarboxylate

Mohammad Hassam ^a,^*, Vincent J Smith ^a

PMCID: PMC3569770 PMID: 23424516

Abstract

In the title compound, C₂₁H₂₀BrNO₅S, the thiophene group is located above the mean plane of the indole ring and displays rotational disorder (i.e. rotation through 180°). The site occupancy of the major component is 0.902 (2), while that of the minor component is 0.098 (2). In the crystal, pairs of weak C—H⋯O interactions link the molecules into centrosymmetric dimers.

Related literature

For background to the use of indoles as scaffolds in the synthesis of HIV-agents, see: Hassam et al. (2012 ▶) and for a recent review on stages of non-nucleoside reverse transcriptase inhibitors, see: Reynolds et al. (2012 ▶). For the crystal structures of closely related compounds, see: Beddoes et al. (1986 ▶), Hassam & Smith (2012 ▶).

Experimental

Crystal data

C₂₁H₂₀BrNO₅S
M _r = 478.35
Monoclinic,
a = 16.220 (3) Å
b = 15.361 (3) Å
c = 18.224 (4) Å
β = 113.792 (2)°
V = 4154.7 (15) Å³
Z = 8
Mo Kα radiation
μ = 2.11 mm⁻¹
T = 100 K
0.34 × 0.21 × 0.17 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan [symmetry-related measurements (SADABS; Bruker, 2009 ▶)] T _min = 0.537, T _max = 0.721
23562 measured reflections
4855 independent reflections
4101 reflections with I > 2σ(I)
R _int = 0.039

Refinement

R[F ² > 2σ(F ²)] = 0.029
wR(F ²) = 0.066
S = 1.05
4855 reflections
279 parameters
13 restraints
H-atom parameters constrained
Δρ_max = 0.38 e Å⁻³
Δρ_min = −0.38 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: X-SEED (Barbour, 2001 ▶; Atwood & Barbour, 2003 ▶); software used to prepare material for publication: X-SEED.

Supplementary Material

Click here for additional data file.^{(31.6KB, cif)}

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536813000809/jj2160sup1.cif

e-69-0o237-sup1.cif^{(31.6KB, cif)}

Click here for additional data file.^{(237.9KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813000809/jj2160Isup2.hkl

e-69-0o237-Isup2.hkl^{(237.9KB, hkl)}

Click here for additional data file.^{(7.3KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813000809/jj2160Isup3.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
C12A—H12A⋯O3ⁱ	0.95	2.48	3.418 (5)	169

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Symmetry code: (i) Inline graphic .

Acknowledgments

MH thanks Professor Willem A. L. van Otterlo and Dr S. C. Pelly for their valuable input and research oversight. Stellenbosch University’s Science Faculty is also acknowledged for providing laboratory space and financial research support (Subcommittee B). The South African National Research Foundation (NRF), Pretoria, is also acknowledged for providing research funds.

supplementary crystallographic information

Comment

Ethyl-5-bromo-1H-indole-2-carboxylate has been employed as a building block in the synthesis of various anti-HIV active molecules, particularly in the search for novel non-nucleoside reverse transcriptase inhibitors (Hassam et al. 2012). Protection on the indole NH of ethyl 5-bromo-3-(2- thiophenoyl)-1H-indole-2-carboxylate was carried out with di-tert -butyl-dicarbonate using 4-dimethylaminopyridine as a catalytic base.

The title compound, C₂₁H₂₀BrNO₅S, crystallizes with one molecule in the asymmetric unit (Fig. 1). The thiophene moiety is disordered over two positions with major (A) and minor (B) components in a 0.9021 (19):0.0979 (19)(2) ratio. The dihedral angles between the mean planes of the 5-bromo indole ring (Br1/N1/C1-C8) and the disordered thiophene rings (S1A/C10/C11A/C13A and S1B/C10/C11B/C13B) are 59.67 (9)° and 60.20 (76)°, respectively. The angles between the mean planes of the indole ring and the N-tert- butyloxy, ethyl ester and the ketone groups are 31.72 (7)°, 45.08 (6)° and 47.88 (7)°, respectively. The torsion angles of O5/C9/C10/S1A and O5/C9/C10/S1B are -20.67 (24)° and 159.92 (34)°, respectively, thereby describing the major component in a cis conformation and the minor component in a trans conformation. Molecular packing shows the molecules forming centrosymmetric dimers linked via weak C12A—H12A···O3 intermolecular interactions (Fig. 2, Table 1).

Experimental

4-dimethylaminopyridine (0.0100 g, 0.0818 mmol) was added to a solution of ethyl 5-bromo-3-(2-thiophenoyl)-1H-indole-2-carboxylate (1.10 g, 2.91 mmol) in THF (20 ml), followed by the addition of di-tert-butyl dicarbonate (1.16 g, 5.32 mmol). The reaction mixture was stirred at 298.15 K for 2 h. Colourless crystals were obtained from a hexane/dichloromethane solvent mixture (4:1) (1.15 g, 83%).