Startseite Crystal structure of 2-(2,3-bis(4-methoxyphenyl)-1H-pyrrolo[2,3-b]quinoxalin-1-yl)anilin, C30H24N4O2
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Crystal structure of 2-(2,3-bis(4-methoxyphenyl)-1H-pyrrolo[2,3-b]quinoxalin-1-yl)anilin, C30H24N4O2

  • Hangzhou Tian , Geyu Chen , Jiejie Ma , Hongjuan Tong ORCID logo und Bin Liu ORCID logo EMAIL logo
Veröffentlicht/Copyright: 1. Oktober 2024

Abstract

C30H24N4O2, triclinic, P 1 (no. 2), a = 8.7813(5) Å, b = 12.2074(7) Å, c = 12.7561(7) Å, α = 112.071(2)°, β = 106.856(2)°, γ = 92.265(2)°, V = 1,195.65(12) Å3, Z = 2, R gt(F) = 0.0586, wR ref(F 2) = 0.1534, T = 170 K.

CCDC no.: 2314041

Table 1 contains crystallographic data and Table 2 contains the list of the atoms including atomic coordinates and displacement parameters.

Table 1:

Data collection and handling.

Crystal: Colourless block
Size: 0.12 × 0.06 × 0.05 mm
Wavelength: Mo Kα radiation (0.71073 Å)
μ: 0.08 mm−1
Diffractometer, scan mode: Bruker APEX-II, φ and ω
θ max, completeness: 26.4°, 99 %
N(hkl)measured, N(hkl)unique, R int: 13,892, 4,848, 0.043
Criterion for I obs, N(hkl)gt: I obs > 2σ(I obs), 3,536
N(param)refined: 315
Programs: Bruker, 1 SHELX, 2 , 3 Olex2 4
Table 2:

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2).

Atom x y z U iso*/U eq
C1 0.1689 (3) 0.4226 (2) −0.0378 (2) 0.0423 (7)
H1C 0.119980 0.447877 −0.102694 0.063*
H1D 0.097207 0.429042 0.009757 0.063*
H1E 0.185255 0.339260 −0.071944 0.063*
C2 0.4062 (3) 0.4748 (2) 0.1329 (2) 0.0288 (5)
C3 0.5553 (3) 0.5477 (2) 0.2025 (2) 0.0341 (6)
H3 0.591757 0.608937 0.182217 0.041*
C4 0.6502 (3) 0.5315 (2) 0.3006 (2) 0.0313 (5)
H4 0.751833 0.581853 0.347244 0.038*
C5 0.5997 (3) 0.44235 (19) 0.33293 (19) 0.0247 (5)
C6 0.4500 (3) 0.3709 (2) 0.2630 (2) 0.0266 (5)
H6 0.412624 0.310291 0.283672 0.032*
C7 0.3537 (3) 0.3861 (2) 0.1632 (2) 0.0278 (5)
H7 0.252183 0.335680 0.116005 0.033*
C8 0.7040 (3) 0.42839 (19) 0.43949 (19) 0.0248 (5)
C9 0.7231 (3) 0.32409 (19) 0.45627 (19) 0.0250 (5)
C10 0.7993 (3) 0.52440 (19) 0.5501 (2) 0.0244 (5)
C11 0.8762 (3) 0.47160 (19) 0.6313 (2) 0.0250 (5)
C12 0.9936 (3) 0.6516 (2) 0.7769 (2) 0.0266 (5)
C13 0.9132 (3) 0.70698 (19) 0.7009 (2) 0.0257 (5)
C14 0.9308 (3) 0.8330 (2) 0.7472 (2) 0.0308 (5)
H14 0.876276 0.870829 0.697735 0.037*
C15 1.0254 (3) 0.9013 (2) 0.8626 (2) 0.0339 (6)
H15 1.035731 0.986222 0.892866 0.041*
C16 1.1077 (3) 0.8467 (2) 0.9371 (2) 0.0337 (6)
H16 1.174275 0.895119 1.016887 0.040*
C17 1.0925 (3) 0.7246 (2) 0.8954 (2) 0.0297 (5)
H17 1.148791 0.688707 0.946224 0.036*
C18 0.6509 (3) 0.1996 (2) 0.3751 (2) 0.0249 (5)
C19 0.6641 (3) 0.1507 (2) 0.2613 (2) 0.0275 (5)
H19 0.719063 0.199304 0.235867 0.033*
C20 0.5989 (3) 0.0325 (2) 0.1841 (2) 0.0293 (5)
H20 0.609535 0.000436 0.106660 0.035*
C21 0.5180 (3) −0.03888 (19) 0.2205 (2) 0.0276 (5)
C22 0.5011 (3) 0.0091 (2) 0.3331 (2) 0.0324 (6)
H22 0.443845 −0.039139 0.357538 0.039*
C23 0.5674 (3) 0.1267 (2) 0.4097 (2) 0.0312 (5)
H23 0.556141 0.158604 0.486942 0.037*
C24 0.5021 (3) −0.2179 (2) 0.0505 (2) 0.0371 (6)
H24A 0.462467 −0.184873 −0.009549 0.056*
H24B 0.458282 −0.303655 0.015691 0.056*
H24C 0.620275 −0.206822 0.076296 0.056*
C25 1.02230 (19) 0.21448 (14) 0.57623 (14) 0.0383 (6)
H25 1.056822 0.236017 0.521514 0.046*
C26 0.89901 (18) 0.26484 (13) 0.61519 (14) 0.0280 (5)
C27 0.84850 (18) 0.23332 (14) 0.69525 (14) 0.0348 (6)
C28 0.9213 (2) 0.15145 (15) 0.73635 (14) 0.0424 (6)
H28 0.886752 0.129913 0.791061 0.051*
C29 1.0446 (2) 0.10109 (14) 0.69738 (17) 0.0478 (7)
H29 1.094303 0.045135 0.725470 0.057*
C30 1.09507 (18) 0.13261 (15) 0.61733 (17) 0.0474 (7)
H30 1.179337 0.098187 0.590697 0.057*
N1 0.7232 (3) 0.2803 (2) 0.7291 (2) 0.0561 (7)
H1A 0.687663 0.258825 0.777503 0.067*
H1B 0.678062 0.332083 0.702537 0.067*
N2 0.8273 (2) 0.34932 (16) 0.57284 (16) 0.0265 (4)
N3 0.9740 (2) 0.52937 (16) 0.74079 (17) 0.0274 (4)
N4 0.8169 (2) 0.64207 (16) 0.58424 (17) 0.0264 (4)
O1 0.3208 (2) 0.49790 (16) 0.03709 (15) 0.0394 (4)
O2 0.4515 (2) −0.15715 (14) 0.15169 (15) 0.0345 (4)

1 Source of materials

To a solution of 3,4-bis(4-methoxyphenyl)cyclobut-3-ene-1,2-dione (2.94 g, 10 mmol) and benzene-1,2-diamine (2.38 g, 22 mmol) in dimethyl sulfoxide (20 mL) was added potassium hydroxide (1.68 g, 30 mmol) and copper powder (32 mg, 0.5 mmol). The mixture was stirred at 120 °C for 12 h, until the TLC indicated the reaction was completed. The mixture was diluted with brine (30 mL), and then extracted with ethyl acetate (3 × 30 mL). The organic phase was washed with brine (30 mL), dried with anhydrous sodium sulphate, and then concentrated under pressure. The title compound was separated by silica-gel column chromatography with methanol – dichloromethane (5 %) gradient solvent system. The target product was obtained as a light red solid. Yield: 68 %. For crystal growth, the product was dissolved in a minimal amount of hot ethanol and slowly cooled to room temperature.

2 Experimental details

Single crystals were obtained by slow evaporation from a solvent mixture. Data collection was performed on a Bruker D8 Venture diffractometer with MoKα radiation (λ = 0.71073 Å). 1 The structure was solved by Direct Methods and refined using SHELX-2014. 2 , 3 , 4 All non-hydrogen atoms were refined anisotropically, and hydrogen atoms were placed in calculated positions and refined using a riding model.

3 Comment

The previous research has demonstrated that pyrrolo[3,2-b]quinoxaline derivatives exhibit low nanomolar affinity towards Eph kinases in vitro and display excellent selectivity within a panel of 453 human kinases (395 non-mutant). 5 To date, only a limited number of crystal structures of pyrrolo[3,2-b]quinoxaline derivatives have been reported. 6 , 7 , 8 , 9 Exploring the crystal structures of pyrrolo[3,2-b]quinoxaline derivatives is crucial for the development of novel therapeutics.

As illustrated in the compound under study, two anisole groups substitute the hydrogen atoms on the C atoms of the pyrrolo[3,2-b]quinoxaline heterocyclic ring, with methoxy groups positioned para. An aniline group replaces the hydrogen atom on the N atom of the pyrrolo[3,2-b]quinoxaline heterocyclic ring, with the amino group located ortho on the benzene ring. The framework atoms of the pyrrolo[3,2-b]quinoxaline moiety are nearly coplanar, consistent with previously reported crystal structures of pyrrolo[3,2-b]quinoxaline derivatives. 10 , 11 , 12 The two anisole and one aniline groups show deviations relative to the pyrrolo[3,2-b]quinoxaline plane, with dihedral angles measured at 37.0°, 55.4°, and 80.1°, respectively.


Corresponding author: Bin Liu, Xianyang Key Laboratory of Molecular Imaging and Drug Synthesis, School of Pharmacy, Shaanxi Institute of International Trade & Commerce, Xianyang, Shaanxi, China, E-mail:

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: Natural Science Foundation of Shannxi Province (2024JC–YBMS-733), Scientific research plan project of Shaanxi Provincial Department of Education (23JK0321), the Xianyang key laboratory of molecular imaging and drug synthesis (2021QXNL–PT-0008), the 2023 key research and development project of the Xianyang Science and Technology Bureau (L2023–ZDYF–SF-030).

  3. Conflict of interest: The authors declare no conflicts of interest regarding this article.

References

1. Bruker. SAINT, APEX2 and SADABS; Bruker AXS Inc.: Madison, WI, USA, 2012.Suche in Google Scholar

2. Sheldrick, G. M. SHELXT – Integrated Space-Group and Crystal-Structure Determination. Acta Crystallogr. 2015, A71, 3–8; https://doi.org/10.1107/s2053273314026370.Suche in Google Scholar PubMed PubMed Central

3. Sheldrick, G. M. Crystal Structure Refinement with SHELXL. Acta Crystallogr. 2015, C71, 3–8, https://doi.org/10.1107/s2053229614024218.Suche in Google Scholar

4. Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A.; Puschmann, H. OLEX2: A Complete Structure Solution, Refinement and Analysis Program. J. Appl. Crystallogr. 2009, 42, 339–341; https://doi.org/10.1107/s0021889808042726.Suche in Google Scholar

5. Unzue, A.; Dong, J.; Lafleur, K.; Zhao, H.; Frugier, E.; Caflisch, A.; Nevado, C. Pyrrolo[3,2-b]quinoxaline Derivatives as Types I1/2 and II Eph Tyrosine Kinase Inhibitors: Structure–Based Design, Synthesis, and In Vivo Validation. J. Med. Chem. 2014, 57, 6834–6844; https://doi.org/10.1021/jm5009242.Suche in Google Scholar PubMed

6. Prasad, B.; Shiva Kumar, K.; Vijaya Babu, P.; Anusha, K.; Rambabu, D.; Kandale, A.; Vanaja, G. R.; Kalle, A. M.; Pal, M. AlCl3 Induced C–N Bond Formation Followed by Pd/C–Cu Mediated Coupling-Cyclization Strategy: Synthesis of Pyrrolo[2,3-B]quinoxalines as Anticancer Agents. Tetrahedron Lett. 2012, 53, 6059–6066; https://doi.org/10.1016/j.tetlet.2012.08.119.Suche in Google Scholar

7. Gryko, D. T.; Piechowska, J.; Vetokhina, V.; Wójcik, D. Fluorescent Dyes with 2-Amino-4,7-Diazaindole Skeleton: Synthesis and Spectroscopy. Bull. Chem. Soc. Jpn. 2009, 82, 1514–1519; https://doi.org/10.1246/bcsj.82.1514.Suche in Google Scholar

8. Gryko, D. T.; Piechowska, J.; Tasior, M.; Waluk, J.; Orzanowska, G. From Bifunctional Nucleophilic Behavior of DBU to a New Heterocyclic Fluorescent Platform. Org. Lett. 2006, 8, 4747–4750; https://doi.org/10.1021/ol061827m.Suche in Google Scholar PubMed

9. Mackenroth, A. V.; Antoni, P. W.; Rominger, F.; Rudolph, M.; Hashmi, A. S. K. Gold-Catalyzed [3,3]-Sigmatropic Rearrangement of Ortho-Alkynyl-S,S-Diarylsulfilimines. Org. Lett. 2023, 25, 2907–2912; https://doi.org/10.1021/acs.orglett.3c00953.Suche in Google Scholar PubMed

10. Bloch, W. M.; Derwent-Smith, S. M.; Issa, F.; Morris, J. C.; Rendina, L. M.; Sumby, C. J. Fused Pyrazino[2,3-B]indolizine and Indolizino[2,3-B]quinoxaline Derivatives; Synthesis, Structures, and Properties. Tetrahedron 2011, 67, 9368–9375; https://doi.org/10.1016/j.tet.2011.09.133.Suche in Google Scholar

11. Keivanloo, A.; Besharati–Seidani, T.; Kaboudin, B.; Yoshida, A.; Yokomatsu, T. One-pot Synthesis of Biologically Active 1,2,3-Trisubstituted Pyrrolo[2,3-B]quinoxalines through a Palladium-Catalyzed Reaction with Internal Alkyne Moieties. Mol. Div. 2018, 22, 879–891; https://doi.org/10.1007/s11030-018-9838-z.Suche in Google Scholar PubMed

12. Nakhi, A.; Rahman, M. S.; Kishore, R.; Meda, C. L. T.; Deora, G. S.; Parsa, K. V. L.; Pal, M. Pyrrolo[2,3-b]quinoxalines as Inhibitors of Firefly Luciferase: Their Cu-Mediated Synthesis and Evaluation as False Positives in a Reporter Gene Assay. Bioorg. Med. Chem. Lett. 2012, 22, 6433–6441; https://doi.org/10.1016/j.bmcl.2012.08.056.Suche in Google Scholar PubMed

Received: 2024-07-29
Accepted: 2024-09-17
Published Online: 2024-10-01
Published in Print: 2024-12-17

© 2024 the author(s), published by De Gruyter, Berlin/Boston

This work is licensed under the Creative Commons Attribution 4.0 International License.

Artikel in diesem Heft

  1. Frontmatter
  2. New Crystal Structures
  3. Crystal structure of 3-nitrophenol-2,1,3-benzoselenadiazole (1/1), C12H9N3O3Se
  4. Crystal structure of diaqua-(hydroxido)-{μ-[2-(hydroxy)-5-[(4-nitrophenyl)diazenyl]benzoato]}-{2-hydroxy-5-[(4-nitrophenyl)diazenyl]benzoato}-(1,10-phenanthroline)-diterbium hydrate, C38H27.4N8O12.2Tb
  5. Crystal structure of poly[bis(μ3-3-fluoro-4-(1H-1,2,4-triazol-1-yl)benzoato-κ3 O:O′:N)cadmium(II)] – dimethylformamide (1/1), C21H17CdF2N7O5
  6. The crystal structure of 2-amino-N-(pyridin-2-yl)benzamide, C12H11N3O
  7. The crystal structure of 2,3-di(pyridin-2-yl)-2,3-dihydroquinazolin-4(1H)-one, C18H14N4O
  8. Crystal structure of 2-chloro-4-fluorobenzyl (R)-2-(6-methoxynaphthalen-2-yl)propanoate, C21H18ClFO3
  9. Crystal structure of [1-(4-carboxyphenyl)-4-oxo-1,4-dihydropyridazine-3-carboxylic acid]-(methylsulfinyl)methane, C15H16N2O6S
  10. The crystal structure of 2-ethyl-1,1-dimethyl-1H-benzo[e]indole, C16H17N
  11. The crystal structure of (Z)-5-amino-N -hydroxy-1H-pyrazole-4-carboximidamide, C4H7N5O
  12. The crystal structure of 2,2,5-trimethyl-3-(4-(4-(5-phenyl-4,5-dihydroisoxazol-3-yl)thiazol-2-yl)phenyl)imidazolidin-4-one, C24H24N4O2S
  13. The crystal structure of tetrakis(μ2-acetato-κ2 O:O′)-bis[(4′-phenyl-4,2′:6′,4″-terpyridine-κ1 N)dicopper(II)], C25H21CuN3O4
  14. Crystal structure of poly(3-thiophenecarboxylato-κ 3 O,O′:O′)-(methanol-κO)cadmium(II), C11H10O5S2Cd
  15. The crystal structure of dichloridobis[4′-(p-methoxylphenyl)-4,2′:6′,4″-terpyridine-κN] zinc(II), C44H34Cl2N6O2Zn
  16. The crystal structure of 1-(2-carboxyethyl)-1H-imidazole 3-oxide
  17. Crystal structure of 1,1′,1″-(nitrilotris(ethane-2,1-diyl))tris(3-(4-(((E)-pyridin-2-ylmethylene)amino)phenyl)urea), C45H47N13O4
  18. Crystal structure of a (E)-4-bromo-N-(4-(diethylamino)-2-hydroxybenzylidene) benzenaminium acetate ─ 4-bromoaniline (1/1)
  19. Crystal structure of 2,2′-(iminobis(methylene))bis(benzimidazolium) bis(p-toluenesulfonate), C30H31N5O6S2
  20. The crystal structure of alogliptinium meta-chlorobenzoate
  21. Crystal structure of 4-bromobenzyl 2-(6-methoxy-naphthalen-2-yl)propanoate, C21H19BrO3
  22. The hydrated double salt structure of (E)-4-(2-benzylidenehydrazine-1-carbonyl)pyridin-1-ium cation with 2-hydroxybenzoate and benzoate anions
  23. Crystal structure of (R)(R)-5-chloro-3-((S,1E,3E)-3,5-dimethyl-hepta-1,3-dien-1-yl)-7-methyl-6,8-dioxo-2,6,7,8-tetrahydroisoquinolin-7-yl acetate, C21H24ClNO4
  24. The crystal structure of bis(3-oxo-1,3-diphenylprop-1-en-1-olato-κ 2 O:O′)-bis(1,4-dioxane-κ 1 O)nickel(II), C38H38O8Ni
  25. Crystal structure of poly[aqua-(pyridine-3-carboxylato-κ1 N)(pyridine-3-carboxylato-κ2 O,O′) cadmium(II)] dihydrate, C12H14N2O7Cd
  26. The crystal structure of 4-(4-phenyl-5-(((1-(2,4,6-tribromophenyl)-1H-1,2,3-triazol-4-yl)methyl)thio)-4H-1,2,4-triazol-3-yl)pyridine, C22H14Br3N7S
  27. The crystal structure of N-benzylquinoline-2-carbothioamide, C17H14N2S
  28. Crystal structure of bis(3-isopropylphenyl)-4,4′-bipyridinium dichloride dihydrate, C28H30N2⋅2Cl⋅2H2O
  29. The crystal structure of ethyl 2-amino-4-(cyanophenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carboxylate, C19H18N2O4
  30. Crystal structure of (4R,10S)-6-hydroxy-7-isopropyl-4,10-dimethyl-1,2,3,5-hexahydro-6,10-epoxyazulen-9-one, C15H22O3
  31. The crystal structure of (E)-(2-(2-hydroxy-3-methoxybenzylidene)aminophenyl)arsonic acid, C14H14AsNO5
  32. The crystal structure of poly[(μ 2-2-aminoisophthalato-κ4O,O′:O″:O″′)-(N-methylpyrrolidone κ1O)-dioxido-uranium(VI)], C13H14N2O7U
  33. The crystal structure of the co-crystal isonicotinamide · terephthalic acid, C8H6O4·2(C6H6N2O)
  34. The crystal structure of (E)-1-phenyl-3-(p-tolylthio)but-2-en-1-one, C17H16OS
  35. The crystal structure of 4,5-bis((Z)-chloro(hydroxyimino)methyl)-1H-imidazol-3-ium chloride monohydrate
  36. The crystal structure of 1,2-bis(4-(dimethylamino)phenyl)ethane-1,2-dione. C18H20N2O2
  37. Crystal structure of 2-chloro-4-fluorobenzyl 2-acetoxybenzoate, C16H12ClFO4
  38. Crystal structure of methyl 1-phenyl-9H-pyrido[3,4-b]indole-3-carboxylate, C19H14N2O2
  39. Crystal structure of (3-(dimethoxymethyl)-5-methoxy-1H-indol-1-yl)(5-fluoro-2-iodophenyl)methanone, C19H17FINO4
  40. Crystal structure of tetrachlorido-bis(1-[(1H-triazole-1-yl)methyl]-1H-benzotriazole-κ2 N:N′)dicopper, C36H32Cu2N24Cl4
  41. Crystal structure of 2-(2,3-bis(4-methoxyphenyl)-1H-pyrrolo[2,3-b]quinoxalin-1-yl)anilin, C30H24N4O2
  42. Crystal structure of 5,7-dihydroxy-2-phenyl-4H-chromen-4-one–N,N-dimethylformamide(1/1), C18H17NO5
  43. The crystal structure of bis(μ 2-biphenyl-2,2′-dicarboxylato)-diaqua-bis(nitrato)-bis(2,2′:6′,2′′-terpyridine)dineodymium(III), C46H32I2N8Nd2O16
  44. Crystal structure of (Z)-4-amino-N -((4-chlorophenyl)(phenyl)methylene)benzohydrazide, C20H16ClN3O
  45. Crystal structure of (E)-6,8-dimethoxy-4-(4-morpholinobenzylidene)-3,4-dihydro-1-benzoxepin-5(2H)-one, C23H25NO5
  46. Crystal structure of (R)-2-((3-(3-aminopiperidin-1-yl)-6-methyl-5-oxo-1,2,4-triazin-4(5H)-yl) methyl)-4-fluorobenzonitrile benzoate monohydrate, C24H27FN6O4
  47. The crystal structure of [triaqua-(8-carboxymethoxy-quinoline-2-carboxylato-κ 3 N,O,O)copper(II)]monohydrate, C12H15NO9Cu
  48. Crystal structure of (((4-chlorophenyl)sulfonyl)glycinato-κ 2 N,O)bis(1,10-phenanthroline-κ 2 N,N′)cobalt(II) tetrahydrate, C32H30ClCoN5O8S
  49. Crystal structure of (((3-nitrophenyl)sulfonyl)-β-alaninato-κO)bis(2,2′-bipyridine-κ 2 N, N′)copper(II) 3-nitrobenzenesulfonate, C35H29CuN7O11S2
  50. Crystal structure of 3-phenoxybenzyl 2-(6-methoxynaphthalen-2-yl)propanoate, C27H24O4
  51. 6-(2′,3′-Dihydroxy-3′-methylbutyl)-7-methoxy-8-(3″-methylbut-2″-en-1″-yl)-2H-chromen-2-one, C20H26O5
  52. Crystal structure of bromido-(2,2′:6′,2″-terpyridine-4′-onato-κ3N)palladium(II) methanol solvate
  53. The crystal structure of ethyl 2-amino-(4-nitrophenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carboxylate, C20H22N2O6
  54. Crystal structure of (1E,3E,5E)-1,6-bis(4-(pentyloxy)phenyl)hexa-1,3,5-triene, C28H36O2
  55. The crystal structure of tris(2-bromo-4-methylphenyl)amine, C21H18Br3N
  56. The crystal structure of 3-(2,5-dimethylanilino)-1-(2,5-dimethylphenyl)-4-methyl-1H-pyrrole-2,5-dione, C21H22N2O2
  57. Crystal structure of dicarbonyl (μ2-indole-2-carboxylato κ2 O:O′)tris(triphenylarsine-κAs)dirhodium(I) acetone solvate, C68H56As3NO5Rh2
  58. The crystal structure of 4-chloro-2-formylphenyl 4-methylbenzenesulfonate, C14H11ClO4S
  59. Crystal structure of 4-iodobenzyl 2-(6-methoxynaphthalen-2-yl) propanoate, C21H19IO3
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