Synthesis of thieno[2,3-b][1,5]benzoxazepine derivatives

A new series of 4-(4-methylpiperazin-1-yl)thieno[2,3-b][1,5]benzoxazepines 1a-k has been synthesized from 4-bromo-2-methylthiophene 6 or ethyl 2-amino-4,5-dimethyl-3-thiophencarboxylate 10. Preparation of the key intermediate thieno[2,3-b][1,5]benzoxazepine-4(5H)-ones 4a-i, 4k were carried out by treatment of 2-bromo-N-(2-hydroxyphenyl)-3-thiophencarboxamides 5a-i, 5k with potassium carbonate in DMSO. Compounds 1 are thienoanalogues of loxapine, a potent antipsychotic drug. Of these compounds, the neu-roleptic activity of 2-methyl-4-(4-methylpiperazin-l-yl)thieno[2,3-b][1,5]benzoxazepine 1a (R1, R3=H, R2=CH3) demonstrated potent antipsychotic activity.