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Synlett 2023; 34(13): 1603-1606
DOI: 10.1055/s-0042-1751440
letter

Syntheses of Oxazolidinone-2,3-Fused Indoline and Azaindoline Derivatives

Koji Yamada 
a   Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
,
Kaho Ishizawa
a   Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
,
Yoshihiro Oonishi 
b   Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo Nishi 6-chome, Kita-ku, Sapporo, Hokkaido 060-0812, Japan
,
Yoshihiro Sato 
b   Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo Nishi 6-chome, Kita-ku, Sapporo, Hokkaido 060-0812, Japan
,
Takahide Nishi  ∗
a   Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
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Abstract

We herein describe a practical synthetic method to access oxazolidinone-2,3-fused indoline and azaindoline derivatives via one-pot cyclization. These derivatives, which contain sp3-hybridized carbons, may be useful as new scaffolds in medicinal chemistry.

Key words

3-bromo-2-hydroxy-1-tosylindoline - 3-bromo-2-hydroxy-1-tosylazaindoline - oxazolidinone - isocyanate - cyclization

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0042-1751440.
  • Supporting Information


Publication History

Received: 23 February 2023

Accepted after revision: 08 March 2023

Article published online:
05 April 2023

© 2023. Thieme. All rights reserved

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  • 12 (2R*,3S*)-3-Bromo-4-chloro-1-tosylindolin-2-ol (1a): Typical Procedure To a solution of 4-chloro-1-tosylindole (4a; 4.00 g, 13.1 mmol) and H2O (2.35 mL, 131 mmol) in acetone (80 mL) was added NBS (2.56 g, 14.4 mmol). The reaction mixture was stirred at room temperature for 7 h. The solvent was removed in vacuo, and the residue was diluted with brine and extracted with EtOAc. The organic layer was dried over MgSO4. The solvent was removed in vacuo, and the residue was purified by flash silica gel column chromatography (n-hexane/EtOAc = 8:1–2:1) to obtain 1a as a white solid (4.74 g, 90% yield); mp 116–118 °C. 1H NMR (500 MHz, CDCl3): δ = 7.75 (d, J = 8.6 Hz, 2 H), 7.48 (d, J = 8.6 Hz, 1 H), 7.27 (m, 1 H), 7.26 (d, J = 8.6 Hz, 2 H), 7.05 (d, J = 8.1 Hz, 1 H), 6.01 (s, 1 H), 5.04 (s, 1 H), 3.73 (brs, 1 H), 2.37 (s, 3 H). 13C NMR (125 MHz, CDCl3): δ = 145.1, 141.3, 135.2, 132.4, 132.2, 130.0, 127.8, 127.3, 125.1, 113.3, 93.5, 47.1, 21.7. HRMS (ESI): m/z [M + Na]+ calcd for C15H13BrClNNaO3S: 423.9386, 425.9365, and 427.9336; found: 423.9405, 425.9366, and 427.9362. (3aR*,8bR*)-8-Chloro-1-phenyl-4-tosyl-1,3a,4,8b-tetrahydro-2H-oxazolo[5,4-b]indol-2-one (2a): Typical Procedure Compound 1a (4.00 g, 9.93 mmol) was heated with phenyl isocyanate (1.77 g, 14.9 mmol) and cesium carbonate (4.84 g, 14.9 mmol) in THF (200 mL) at 80 °C for 2 h. The reaction mixture was diluted with EtOAc and washed with brine. The organic layer was dried over MgSO4. The solvent was removed in vacuo and the residue was crystallized from MeOH to obtain 2a as a white solid (3.63 g, 83% yield); mp 210–212 °C. 1H NMR (500 MHz, CDCl3): δ = 7.96 (d, J = 8.6 Hz, 2 H), 7.36 (d, J = 8.6 Hz, 2 H), 7.30–7.39 (m, 3 H), 7.20–7.25 (m, 4 H), 6.86 (d, J = 8.0 Hz, 1 H), 6.80 (d, J = 7.5 Hz, 1 H), 5.85 (d, J = 7.5 Hz, 1 H), 2.43 (s, 3 H). 13C NMR (125 MHz, CDCl3): δ = 154.4, 145.4, 142.5, 136.2, 135.4, 132.4, 132.2, 130.3, 129.4, 128.3, 127.9, 127.3, 125.3, 124.7, 112.0, 88.1, 62.2, 21.8. HRMS (ESI): m/z [M + Na]+ calcd for C22H17ClN2NaO4S: 463.0495 and 465.0466; found: 463.0492 and 465.0476.