Polyaryl antitumor agents

Chang etaU US Patent 6,046,229 (April 4, 2000) Assignee Industrial Technology Research Institute Utility Anti-Neoplastic Agents for Inoperable or Metastatic Cancers 

A mixture of 5 ml N,N-dimethylformamide and phosphorous oxychloride (1.74 mmol) were stirred 30 minutes in an ice bath, (E)-l,2-bis(2-thienyl)ethene (1.58mmol) added, and the mixture stirred at 50°C for 48 hours. The mixture was cooled to ambient temperature, 10 ml 10% NaHC03 added, and extracted with CH2CI2. The extract was washed with brine, dried, filtered and concentrated. The residue was purified by chromatography using silica gel with EtOAc/n-hexane, recrystallized in EtOAc, and the product isolated in 6% yield, mp = 209 °C. H-NMR and MS data supplied. 

The product from Step 1 (5 mmol) was added to a mixture of 30 ml methyl alcohol and ethanolamine (10 mmol) containing several drops of HO Ac. Thereafter, NaBH4 was added, the mixture concentrated, and the residue treated with 50 ml apiece EtOAc and 0.1 N HCl. The mixture was filtered, washed with EtOAc, treated with 2 M NaOH until a pH 12 observed, and re-extracted with EtOAc. The extract was washed with NaHC03, brine, dried, and concentrated. It was re-crystallized in n-hexane, and 1.22 g product isolated, mp = 91 °C. H-NMR, MS, and IR data supplied. 

Thiophenes were formylated by the insitu generation of the Vilsmeiser-Haack reagent, MeN+ = CHCl (2). 

The preparation of l,2-bis[2-(5-formyl)- and 5-(bydroxylmethyl)-thienyl]acetylene derivatives are also described by the author. 

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