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Crystal structure of 5-benzyl-8-bromo-2-meth­yl-1,3-oxazolo[4,5-c][1,8]naphthyridin-4(5H)-one

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aKU Leuven - University of Leuven, Department of Chemistry, Celestijnenlaan 200F - bus 2404, B-3001 Heverlee, Belgium
*Correspondence e-mail: luc.vanmeervelt@kuleuven.be

Edited by C. Rizzoli, Universita degli Studi di Parma, Italy (Received 24 March 2017; accepted 31 March 2017; online 11 April 2017)

The title compound, C17H12BrN3O2, was unexpectedly isolated during an attempt to synthesize pyridodiazepinediones and identified as an oxazolonaphthyridinone derivative. The almost planar oxazolonaphthyridinone ring (r.m.s. deviation = 0.016 Å) makes a dihedral angle of 61.6 (2)° with the phenyl ring. In the crystal, columns of mol­ecules stacked along the a axis are formed by ππ inter­actions between the six-membered rings of the oxazolonaphthyridone moieties [centroid-to-centroid distances = 3.494 (2)–3.906 (3) Å], which further inter­act through C—H⋯π contacts with the phenyl rings.

1. Chemical context

While benzodiazepine drugs have been amongst the most prescribed medication globally since their discovery in the 1950s, the search for structurally related biologically active compounds is of major relevance to the pharmaceutical industry (Washton & Zweben, 2011[Washton, A. M. & Zweben, J. E. (2011). Treating Alcohol and Drug Problems in Psychotherapy Practice, p. 47. New York: Guilford Press.]). Previous work in our group dealing with the construction of pyridodiazepinediones (PZDs; Van den Bogaert et al., 2010[Van den Bogaert, A. M., Nelissen, J., Ovaere, M., Van Meervelt, L., Compernolle, F. & De Borggraeve, W. M. (2010). Eur. J. Org. Chem. pp. 5397-5401.]) led unexpectedly to the isolation of a tricyclic compound, which was later identified as oxazolonaphthyridinone (ONO) 6 (Fig. 1[link]). Commercially available 2-hy­droxy­nicotinic acid 1 was converted to dihalonicotinic acid 3 via two sequential halogenation reactions (Van den Bogaert et al., 2010[Van den Bogaert, A. M., Nelissen, J., Ovaere, M., Van Meervelt, L., Compernolle, F. & De Borggraeve, W. M. (2010). Eur. J. Org. Chem. pp. 5397-5401.]; Gero et al., 1989[Gero, T. W., Jaques, L. W., Mays, R. P., Reid, D. H., Shamblee, D. A. & Lo, Y. S. (1989). Synth. Commun. 19, 553-559.]; Haché et al., 2002[Haché, B., Duceppe, J. S. & Beaulieu, P. L. (2002). Synthesis, pp. 528-532.]), after which a benzyl­amine substituent was introduced yielding the aza-anthranilic acid derivative 4. Next, ester compound 5 was prepared from inter­mediate 4 and tert-butyl glycinate using a standard coupling procedure. Finally, tert-butyl ester 5 was deprotected in situ and reacted with acetic anhydride in the presence of potassium carbonate, yielding tricyclic compound 6. After exploration and optimization of the revealed cascade reaction towards the closely related oxazolo­quinolinone scaffold (Vrijdag et al., 2013[Vrijdag, J. L., Van den Bogaert, A. M. & De Borggraeve, W. M. (2013). Org. Lett. 15, 1052-1055.]), we decided to turn our attention to the remarkable tricyclic product 6 isolated during the initial investigation. The ONO structural motif contained in compound 6 is brought into relation with both anti­bacterial (Ratcliffe et al., 2015[Ratcliffe, A., Huxley, A., Lyth, D., Noonan, G., Kirk, R., Uosis-Martin, M. & Stokes, N. (2015). WO Patent 155549.]) and histamine 4 receptor antagonist (Ho et al., 2013[Ho, P. S., Yoon, D. O., Han, S. Y., Lee, W. I., Kim, J. S., Park, W. S., Ahn, S. O. & Kim, H. J. (2013). WO Patent 048214.]) activities. Hence, new synthetic routes towards ONOs are currently being developed in our laboratory (Vrijdag et al., 2017[Vrijdag, J. L., De Ruysscher, D. & De Borggraeve, W. M. (2017). Eur. J. Org. Chem. pp. 1465-1474.]). Here we present the mol­ecular and crystal structure of the title compound 6.

[Scheme 1]
[Figure 1]
Figure 1
Synthesis of the title compound 6 as unexpectedly formed during the synthesis of pyridodiazepinediones.

2. Structural commentary

Crystals of 6 belong to the ortho­rhom­bic space group Pna21 with one mol­ecule in the asymmetric unit (Fig. 2[link]). The oxazolonaphthyridine ring is almost planar (r.m.s. deviation = 0.016 Å) with the substituents C14 [0.082 (6) Å], O15 [−0.023 (4) Å], Br16 [−0.012 (1) Å] and C17 [0.034 (5) Å] situated in the same plane (deviations from plane given in parenthesis). The dihedral angle between the mean planes through the oxazole and pyridine rings is 2.0 (2)°. The dihedral angle between the oxazolonaphthyridine ring system and the phenyl rings is 61.6 (2)°. Both H atoms of C17 are in close contact with the neighboring atoms N8 and O15 (H17A⋯N8 = 2.36 Å and H17B⋯O15 = 2.36 Å). No classical hydrogen bonds are observed.

[Figure 2]
Figure 2
View of the asymmetric unit of the title compound 6, showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are shown as small circles of arbitrary radii.

3. Supra­molecular features

The crystal packing (Fig. 3[link]) is characterized by ππ inter­actions between the six-membered rings of the oxazolonaphthyridone ring systems, resulting in columns of stacked mol­ecules along the a axis [Fig. 4[link]; Cg1⋯Cg1i = 3.494 (2) Å and Cg2⋯Cg2i = 3.906 (3) Å; Cg1 and Cg2 are the centroids of the rings C7/N8/C9–C12 and C4/C5/N6/C7/C12/C13, respectively; symmetry code: (i) x + [{1\over 2}], −y + [{3\over 2}], z]. Mol­ecules in neighboring columns show further C—H⋯π inter­actions between the C18–C23 phenyl rings (Fig. 3[link], Table 1[link]). The closest contact of Br16 in the packing is with atom O15ii [2.874 (4) Å; symmetry code: (ii) −x + [{1\over 2}], y − [{1\over 2}], z − [{1\over 2}]].

Table 1
Hydrogen-bond geometry (Å, °)

Cg3 is the centroid of the C18–C23 ring.

D—H⋯A D—H H⋯A DA D—H⋯A
C21—H21⋯Cg3i 0.95 2.82 3.604 (6) 141
C11—H11⋯Cg3ii 0.95 3.31 4.239 (6) 167
Symmetry codes: (i) [x-{\script{1\over 2}}, -y+{\script{5\over 2}}, z]; (ii) [x+{\script{1\over 2}}, -y+{\script{3\over 2}}, z].
[Figure 3]
Figure 3
View of the crystal packing for the title compound 6, showing C—H⋯π inter­actions (red dotted lines) between the C18–C23 phenyl rings.
[Figure 4]
Figure 4
Part of the crystal packing of the title compound 6, showing ππ inter­actions between the C7/N8/C9–C12 (blue) and C4/C5/N6/C7/C12/C13 (yellow) rings.

4. Database survey

A search of the Cambridge Structural Database (CSD, Version 5.38, last update February 2017; Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]) for a [1,3]oxazolo[4,5-c]-1,8-naphthyridin-4(5H)-one ring skeleton gave no hits. The closest ring skeleton is found in 2,5-dimeth­yl[1,3]oxazolo[4,5-c]quinolin-4(5H)-one (refcode HOJTUW; Latypov et al., 2008[Latypov, S., Balandina, A., Boccalini, M., Matteucci, A., Usachev, K. & Chimichi, S. (2008). Eur. J. Org. Chem. pp. 4640-4646.]), which contains a quinolinone ring system instead of a naphthyridinone ring system. The oxazolo­quinoline ring is almost planar (r.m.s. deviation = 0.015 Å) with a dihedral angle between the oxazole and phenyl rings of 1.90 (13)°.

5. Synthesis and crystallization

Synthesis of 5-bromo-2-hy­droxy­nicotinic acid (2), 5-bromo-2-chloro­nicotinic acid (3), and 2-(benzyl­amino)-5-bromo­nicotinic acid (4):

Substituted nicotinic acids 2–4 were synthesized following the protocols of Van den Bogaert et al. (2010[Van den Bogaert, A. M., Nelissen, J., Ovaere, M., Van Meervelt, L., Compernolle, F. & De Borggraeve, W. M. (2010). Eur. J. Org. Chem. pp. 5397-5401.]). Analytical data matches literature data.

Synthesis of tert-but­yl N-{[2-(benzyl­amino)-5-bromo­pyridin-3-yl]carbon­yl}glycinate (5):

2-(Benzyl­amino)-5-bromo­nicotinic acid 4 (50 mg, 0.16 mmol) was dissolved in di­methyl­formamide under an Ar atmosphere, and di-iso­propyl­ethyl­amine (27 µl, 0.16 mmol) and benzotriazolyl tetra­methyl­uronium fluoro­borate (TBTU, 57 mg, 0.18 mmol) were subsequently added to the mixture. The reaction was stirred at room temperature for 15 m, and t-butyl glycinate (24 µl, 0.18 mmol) was added. The reaction was continued at room temperature for 18 h, after which the mixture was concentrated under reduced pressure. The residue was purified using silica gel chromatography (hepta­ne/ethyl acetate, 8:2 v/v) to yield compound 5 (64 mg, yield 95%).

IR (Perkin–Elmer 1720 FTIR, KBr, cm−1): ν = 1705 (s, CO ester), 1648 (s, CO amide). 1H NMR [Bruker 400 Avance, 400 MHz, CDCl3, δ (ppm), J (Hz)]: 8.42 (t, 1H, J = 5, CH), 8.21 (d, 1H, J = 2, CH), 7.76 (d, 1H, J = 2, CH), 7.34–7.22 (m, 5H, CH), 6.84 (t, 1H, J = 5, CH), 4.65 (d, 2H, J = 6, CH2), 4.02 (d, 2H, J = 5, CH2), 1.49 (s, 9H, CH3). 13C NMR [Bruker 400 Avance, 101 MHz, CDCl3, δ (ppm)]: 169.4, 167.1, 156.3, 152.6, 139.3, 137.6, 128.6, 127.6, 127.1, 110.6, 104.4, 82.9, 45.0, 42.3, 28.1.

Synthesis of 5-benzyl-8-bromo-2-meth­yl[1,3]oxazolo[4,5-c]-1,8-naphthyridin-4(5H)-one (6):

A mixture of tert-butyl N-{[2-(benzyl­amino)-5-bromo­pyridin-3-yl]carbon­yl}glycinate 5 (50 mg, 0.12 mmol) and di­chloro­methane (2.25 mL) was cooled to 273 K, after which tri­fluoro­acetic acid (0.75 mL) was added. The reaction was continued at room temperature for 16 h, concentrated under reduced pressure, and dried under high vacuum. The obtained crude acid was combined with K2CO3 (38 mg, 0.28 mmol) and acetic anhydride (0.5 mL) under an Ar atmosphere and the mixture was stirred at room temperature for 30 m. Subsequently the reaction was heated to reflux for 24 h, after which the mixture was concentrated under reduced pressure. The residue was purified using silica gel chromatography (di­chloro­methane/methanol, 99:1 v/v) to yield the title compound (12 mg, yield 27%). Light-brown prismatic crystals were grown by diffusion of pentane in a chloro­form solution of the title compound.

IR (Perkin–Elmer 1720 FTIR, NaCl, cm−1): ν = 1683 (s, CO amide). 1H NMR [Bruker 400 Avance, 400 MHz, CDCl3, δ (ppm), J (Hz)]: 8.65 (d, 1H, J = 2, CH), 8.27 (d, 1H, J = 2, CH), 7.48 (dd, 2H, J = 7, 1, CH), 7.26–7.21 (m, 3H, CH), 5.80 (s, 2H, CH2), 2.71 (s, 3H, CH3). 13C NMR [Bruker 400 Avance, 101 MHz, CDCl3, δ (ppm)]: 164.6, 157.3, 150.2, 149.9, 146.6, 137.5, 131.5, 131.0, 128.9, 128.4, 127.5, 113.9, 108.5, 44.8, 14.5.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. All H atoms were placed in calculated positions with C—H = 0.95 Å for aromatic, C—H = 0.98 Å for CH3 or C—H = 0.99 Å for CH2 H atoms, and included in the refinement in a riding model with Uiso(H) = 1.2 or 1.5Ueq(C).

Table 2
Experimental details

Crystal data
Chemical formula C17H12BrN3O2
Mr 370.21
Crystal system, space group Orthorhombic, Pna21
Temperature (K) 200
a, b, c (Å) 6.7150 (13), 13.504 (3), 16.757 (3)
V3) 1519.5 (5)
Z 4
Radiation type Mo Kα
μ (mm−1) 2.72
Crystal size (mm) 0.3 × 0.3 × 0.2
 
Data collection
Diffractometer Enraf–Nonius CAD-4
Absorption correction ψ scan (North et al., 1968[North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351-359.])
Tmin, Tmax 0.522, 0.578
No. of measured, independent and observed [I > 2σ(I)] reflections 1429, 1429, 1279
Rint 0.049
(sin θ/λ)max−1) 0.601
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.027, 0.069, 1.16
No. of reflections 1429
No. of parameters 209
No. of restraints 1
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.34, −0.27
Absolute structure No quotients, so Flack parameter determined by classical intensity fit
Absolute structure parameter 0.000 (12)
Computer programs: CAD-4 EXPRESS (Enraf–Nonius, 1989[Enraf-Nonius (1989). CAD-4 EXPRESS. Enraf-Nonius, Delft, The Netherlands.]), DREAR (Blessing, 1987[Blessing, R. H. (1987). Crystallogr. Rev. 1, 3-58.]), SHELXS (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), SHELXL2014/7 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]) and OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]).

Supporting information


Computing details top

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1989); cell refinement: CAD-4 EXPRESS (Enraf–Nonius, 1989); data reduction: DREAR (Blessing, 1987); program(s) used to solve structure: SHELXS (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014/7 (Sheldrick, 2015); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

5-Benzyl-8-bromo-2-methyl[1,3]oxazolo[4,5-c]-1,8-naphthyridin-4(5H)-one top
Crystal data top
C17H12BrN3O2Dx = 1.618 Mg m3
Mr = 370.21Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pna21Cell parameters from 25 reflections
a = 6.7150 (13) Åθ = 1.9–25.3°
b = 13.504 (3) ŵ = 2.72 mm1
c = 16.757 (3) ÅT = 200 K
V = 1519.5 (5) Å3Prism, light brown
Z = 40.3 × 0.3 × 0.2 mm
F(000) = 744
Data collection top
Enraf–Nonius CAD-4
diffractometer
1279 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.049
Graphite monochromatorθmax = 25.3°, θmin = 1.9°
ω/2θ scansh = 08
Absorption correction: ψ scan
(North et al., 1968)
k = 016
Tmin = 0.522, Tmax = 0.578l = 020
1429 measured reflections3 standard reflections every 97 reflections
1429 independent reflections intensity decay: 0.5%
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.027 w = 1/[σ2(Fo2) + (0.0221P)2 + 0.5935P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.069(Δ/σ)max < 0.001
S = 1.16Δρmax = 0.34 e Å3
1429 reflectionsΔρmin = 0.27 e Å3
209 parametersAbsolute structure: No quotients, so Flack parameter determined by classical intensity fit
1 restraintAbsolute structure parameter: 0.000 (12)
Primary atom site location: structure-invariant direct methods
Special details top

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

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.1853 (5)0.6350 (2)1.0622 (2)0.0353 (7)
C20.1680 (7)0.6538 (4)1.1434 (3)0.0408 (11)
N30.1585 (6)0.7463 (3)1.1614 (2)0.0430 (10)
C40.1733 (6)0.7940 (4)1.0879 (3)0.0344 (10)
C50.1745 (8)0.8991 (4)1.0713 (3)0.0347 (11)
N60.1944 (5)0.9220 (3)0.9912 (2)0.0311 (8)
C70.2122 (7)0.8525 (3)0.9299 (3)0.0261 (10)
N80.2338 (5)0.8876 (3)0.8560 (3)0.0324 (8)
C90.2503 (6)0.8216 (4)0.7968 (3)0.0352 (10)
H90.26590.84540.74380.042*
C100.2456 (6)0.7205 (3)0.8090 (3)0.0327 (10)
C110.2253 (6)0.6834 (3)0.8840 (3)0.0299 (9)
H110.22320.61400.89290.036*
C120.2078 (6)0.7493 (3)0.9470 (2)0.0269 (9)
C130.1890 (6)0.7265 (3)1.0287 (3)0.0299 (9)
C140.1651 (9)0.5668 (5)1.1959 (4)0.0590 (16)
H14A0.13280.58761.25040.089*
H14B0.29620.53501.19530.089*
H14C0.06430.51991.17700.089*
O150.1582 (6)0.9635 (3)1.1226 (2)0.0501 (9)
Br160.26869 (6)0.63431 (3)0.72061 (4)0.04509 (16)
C170.2032 (7)1.0293 (3)0.9709 (3)0.0359 (10)
H17A0.29121.03830.92410.043*
H17B0.26341.06561.01630.043*
C180.0019 (6)1.0740 (3)0.9526 (3)0.0360 (10)
C190.1165 (8)1.1102 (4)1.0132 (4)0.0456 (13)
H190.07521.10331.06710.055*
C200.2946 (10)1.1562 (5)0.9957 (5)0.0567 (18)
H200.37481.18101.03790.068*
C210.3576 (8)1.1669 (4)0.9187 (4)0.0534 (15)
H210.48041.19900.90750.064*
C220.2419 (8)1.1307 (4)0.8573 (4)0.0514 (16)
H220.28401.13800.80350.062*
C230.0632 (8)1.0834 (4)0.8746 (3)0.0476 (13)
H230.01521.05720.83240.057*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0308 (15)0.0340 (17)0.0412 (18)0.0005 (12)0.0015 (14)0.0023 (14)
C20.029 (2)0.053 (3)0.040 (3)0.003 (2)0.001 (2)0.006 (2)
N30.031 (2)0.060 (3)0.037 (2)0.0057 (18)0.0035 (18)0.001 (2)
C40.022 (2)0.043 (3)0.038 (3)0.006 (2)0.0047 (19)0.008 (2)
C50.028 (3)0.039 (3)0.037 (3)0.001 (2)0.008 (2)0.012 (2)
N60.0261 (17)0.0250 (18)0.042 (2)0.0009 (15)0.0004 (16)0.0089 (16)
C70.018 (2)0.028 (2)0.033 (2)0.0013 (18)0.0012 (19)0.0084 (19)
N80.0262 (17)0.030 (2)0.041 (2)0.0006 (14)0.0026 (16)0.0028 (17)
C90.028 (2)0.042 (3)0.035 (2)0.0009 (19)0.0039 (19)0.006 (2)
C100.022 (2)0.034 (2)0.042 (2)0.0003 (17)0.0011 (18)0.0154 (19)
C110.022 (2)0.027 (2)0.041 (2)0.0004 (18)0.0027 (18)0.0099 (19)
C120.0164 (19)0.027 (2)0.037 (2)0.0007 (15)0.0006 (17)0.0069 (18)
C130.0204 (19)0.027 (2)0.043 (3)0.0006 (16)0.0016 (18)0.0008 (18)
C140.053 (3)0.072 (4)0.053 (3)0.006 (3)0.003 (2)0.022 (3)
O150.057 (2)0.049 (2)0.044 (2)0.0047 (18)0.0070 (18)0.0256 (17)
Br160.0427 (2)0.0502 (3)0.0424 (2)0.0015 (2)0.0038 (4)0.0214 (3)
C170.036 (2)0.023 (2)0.049 (3)0.0021 (17)0.002 (2)0.011 (2)
C180.035 (2)0.020 (2)0.052 (3)0.0044 (17)0.002 (2)0.002 (2)
C190.045 (3)0.038 (3)0.054 (3)0.007 (2)0.011 (3)0.002 (2)
C200.049 (4)0.043 (3)0.078 (5)0.013 (3)0.014 (4)0.008 (3)
C210.037 (3)0.032 (3)0.092 (5)0.001 (2)0.009 (3)0.007 (3)
C220.056 (4)0.040 (3)0.058 (4)0.010 (3)0.011 (3)0.006 (2)
C230.053 (3)0.033 (3)0.056 (3)0.003 (2)0.003 (3)0.003 (2)
Geometric parameters (Å, º) top
O1—C21.389 (6)C11—C121.386 (6)
O1—C131.358 (5)C12—C131.408 (6)
C2—N31.287 (6)C14—H14A0.9800
C2—C141.467 (7)C14—H14B0.9800
N3—C41.393 (6)C14—H14C0.9800
C4—C51.446 (7)C17—H17A0.9900
C4—C131.352 (6)C17—H17B0.9900
C5—N61.384 (7)C17—C181.512 (6)
C5—O151.229 (6)C18—C191.379 (7)
N6—C71.396 (6)C18—C231.383 (7)
N6—C171.489 (6)C19—H190.9500
C7—N81.335 (7)C19—C201.380 (9)
C7—C121.423 (6)C20—H200.9500
N8—C91.338 (6)C20—C211.365 (10)
C9—H90.9500C21—H210.9500
C9—C101.381 (7)C21—C221.379 (9)
C10—C111.359 (7)C22—H220.9500
C10—Br161.890 (4)C22—C231.390 (7)
C11—H110.9500C23—H230.9500
C13—O1—C2103.9 (4)C4—C13—C12125.0 (4)
O1—C2—C14116.2 (4)C2—C14—H14A109.5
N3—C2—O1114.3 (4)C2—C14—H14B109.5
N3—C2—C14129.5 (5)C2—C14—H14C109.5
C2—N3—C4103.8 (4)H14A—C14—H14B109.5
N3—C4—C5128.6 (4)H14A—C14—H14C109.5
C13—C4—N3110.1 (4)H14B—C14—H14C109.5
C13—C4—C5121.3 (4)N6—C17—H17A108.9
N6—C5—C4114.0 (4)N6—C17—H17B108.9
O15—C5—C4124.1 (5)N6—C17—C18113.6 (3)
O15—C5—N6121.9 (5)H17A—C17—H17B107.7
C5—N6—C7124.8 (4)C18—C17—H17A108.9
C5—N6—C17116.3 (4)C18—C17—H17B108.9
C7—N6—C17118.9 (4)C19—C18—C17120.4 (5)
N6—C7—C12120.6 (4)C19—C18—C23118.8 (5)
N8—C7—N6116.9 (4)C23—C18—C17120.8 (5)
N8—C7—C12122.5 (4)C18—C19—H19119.9
C7—N8—C9117.4 (4)C18—C19—C20120.2 (6)
N8—C9—H9118.4C20—C19—H19119.9
N8—C9—C10123.1 (5)C19—C20—H20119.4
C10—C9—H9118.4C21—C20—C19121.1 (6)
C9—C10—Br16119.4 (4)C21—C20—H20119.4
C11—C10—C9120.3 (4)C20—C21—H21120.2
C11—C10—Br16120.4 (3)C20—C21—C22119.5 (6)
C10—C11—H11120.8C22—C21—H21120.2
C10—C11—C12118.5 (4)C21—C22—H22120.2
C12—C11—H11120.8C21—C22—C23119.5 (6)
C11—C12—C7118.2 (4)C23—C22—H22120.2
C11—C12—C13127.5 (4)C18—C23—C22120.8 (6)
C13—C12—C7114.3 (4)C18—C23—H23119.6
O1—C13—C12127.1 (4)C22—C23—H23119.6
C4—C13—O1107.9 (4)
O1—C2—N3—C40.9 (6)N8—C9—C10—C110.6 (7)
C2—O1—C13—C40.3 (4)N8—C9—C10—Br16179.6 (3)
C2—O1—C13—C12179.0 (4)C9—C10—C11—C120.6 (6)
C2—N3—C4—C5179.0 (5)C10—C11—C12—C70.1 (6)
C2—N3—C4—C130.7 (5)C10—C11—C12—C13178.8 (4)
N3—C4—C5—N6179.1 (4)C11—C12—C13—O10.4 (7)
N3—C4—C5—O151.4 (8)C11—C12—C13—C4179.7 (4)
N3—C4—C13—O10.2 (5)C12—C7—N8—C90.5 (6)
N3—C4—C13—C12179.6 (4)C13—O1—C2—N30.8 (5)
C4—C5—N6—C70.0 (7)C13—O1—C2—C14178.6 (4)
C4—C5—N6—C17178.1 (4)C13—C4—C5—N60.5 (6)
C5—C4—C13—O1179.5 (4)C13—C4—C5—O15179.0 (5)
C5—C4—C13—C120.1 (7)C14—C2—N3—C4178.4 (5)
C5—N6—C7—N8178.8 (4)O15—C5—N6—C7179.5 (5)
C5—N6—C7—C120.9 (7)O15—C5—N6—C172.4 (7)
C5—N6—C17—C1891.6 (5)Br16—C10—C11—C12179.7 (3)
N6—C7—N8—C9179.8 (4)C17—N6—C7—N80.8 (6)
N6—C7—C12—C11179.8 (4)C17—N6—C7—C12179.0 (4)
N6—C7—C12—C131.3 (6)C17—C18—C19—C20176.1 (5)
N6—C17—C18—C1986.4 (5)C17—C18—C23—C22175.5 (4)
N6—C17—C18—C2396.4 (5)C18—C19—C20—C210.1 (9)
C7—N6—C17—C1890.2 (5)C19—C18—C23—C221.7 (7)
C7—N8—C9—C100.1 (6)C19—C20—C21—C220.3 (10)
C7—C12—C13—O1178.4 (4)C20—C21—C22—C230.4 (8)
C7—C12—C13—C40.9 (6)C21—C22—C23—C181.4 (8)
N8—C7—C12—C110.5 (6)C23—C18—C19—C201.1 (7)
N8—C7—C12—C13178.5 (4)
Hydrogen-bond geometry (Å, º) top
Cg3 is the centroid of the C18–C23 ring.
D—H···AD—HH···AD···AD—H···A
C21—H21···Cg3i0.952.823.604 (6)141
C11—H11···Cg3ii0.953.314.239 (6)167
Symmetry codes: (i) x1/2, y+5/2, z; (ii) x+1/2, y+3/2, z.
 

Acknowledgements

JV and AVDB thank the Research Foundation - Flanders (FWO) for scholarships received. We are grateful to K. Duerinckx (KU Leuven) for assistance with the NMR measurements.

Funding information

Funding for this research was provided by: Fonds Wetenschappelijk Onderzoek.

References

First citationBlessing, R. H. (1987). Crystallogr. Rev. 1, 3–58.  CrossRef Google Scholar
First citationDolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationEnraf–Nonius (1989). CAD-4 EXPRESS. Enraf–Nonius, Delft, The Netherlands.  Google Scholar
First citationGero, T. W., Jaques, L. W., Mays, R. P., Reid, D. H., Shamblee, D. A. & Lo, Y. S. (1989). Synth. Commun. 19, 553–559.  CrossRef CAS Web of Science Google Scholar
First citationGroom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179.  Web of Science CSD CrossRef IUCr Journals Google Scholar
First citationHaché, B., Duceppe, J. S. & Beaulieu, P. L. (2002). Synthesis, pp. 528–532.  Google Scholar
First citationHo, P. S., Yoon, D. O., Han, S. Y., Lee, W. I., Kim, J. S., Park, W. S., Ahn, S. O. & Kim, H. J. (2013). WO Patent 048214.  Google Scholar
First citationLatypov, S., Balandina, A., Boccalini, M., Matteucci, A., Usachev, K. & Chimichi, S. (2008). Eur. J. Org. Chem. pp. 4640–4646.  Web of Science CSD CrossRef Google Scholar
First citationNorth, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359.  CrossRef IUCr Journals Web of Science Google Scholar
First citationRatcliffe, A., Huxley, A., Lyth, D., Noonan, G., Kirk, R., Uosis-Martin, M. & Stokes, N. (2015). WO Patent 155549.  Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationVan den Bogaert, A. M., Nelissen, J., Ovaere, M., Van Meervelt, L., Compernolle, F. & De Borggraeve, W. M. (2010). Eur. J. Org. Chem. pp. 5397–5401.  CSD CrossRef Google Scholar
First citationVrijdag, J. L., De Ruysscher, D. & De Borggraeve, W. M. (2017). Eur. J. Org. Chem. pp. 1465–1474.  Web of Science CrossRef Google Scholar
First citationVrijdag, J. L., Van den Bogaert, A. M. & De Borggraeve, W. M. (2013). Org. Lett. 15, 1052–1055.  Web of Science CrossRef CAS PubMed Google Scholar
First citationWashton, A. M. & Zweben, J. E. (2011). Treating Alcohol and Drug Problems in Psychotherapy Practice, p. 47. New York: Guilford Press.  Google Scholar

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