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. 2010 Aug 25;51(34):4566-4569.
doi: 10.1016/j.tetlet.2010.06.116.

Two step syntheses of fused quinoxaline-benzodiazepines and bis-benzodiazepines

Zhigang Xu  1 , Justin Dietrich, Arthur Y Shaw, Christopher Hulme
Affiliations

Two step syntheses of fused quinoxaline-benzodiazepines and bis-benzodiazepines

Zhigang Xu et al. Tetrahedron Lett. .

Abstract

A two-step solution phase synthesis employing a double UDC (Ugi/Deprotect/Cyclize) strategy has been utilized to obtain fused 6,7,6,6-quinoxalinone-benzodiazepines and 6,7,7,6-bis-benzodiazepines. Optimization of the methodology to produce these tetracyclic scaffolds was enabled by microwave irradiation, incorporation of trifluoroethanol as solvent, and the use of the convertible isocyanide, 4-tert-butyl cyclohexen-1-yl isocyanide.

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Figures

Figure 1
Figure 1
Targeted fused tetracyclic quinoxalinone-benzodiazepines 1, and bis-benzodiazepines 2.
Figure 2
Figure 2
Structures of bicyclic quinoxalinone-benzodiazepines (Ugi % yield, Cyclization % yield).
Figure 3
Figure 3
Structures of fused bis-benzodiazepines (Ugi % yield, Cyclization % yield).
Scheme 1
Scheme 1
Initial synthetic route to scaffold 1.
Scheme 2
Scheme 2
Proposed mechanism of synthesizing benzodiazepines.
Scheme 3
Scheme 3
New process of synthesizing compound 1.
Scheme 4
Scheme 4
Route to fused bis-benzodiazepine 2.
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