A practical synthesis of 1,3,4,14b-tetrahydro-2-methyl-10H-pyrazino-[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepine (1:1) maleate

A practical synthesis of the anti-depressant, 1,3,4,14b-tetrahydro-2-methyl-10H-pyrazino1,2-a]pyrrolo-2,1-c]1,4]benzodiazepine (1:1) maleate (Aptazapine 10 ) is reported in seven steps and approximately 20% overall yield. The key step of the synthesis was the formation of the tricyclic intermediate methyl 10,11-dihydro-5H-pyrrolo2,1-c]1,4]benzodiazepine-11-carboxylate (7) via a “Pictet-Spengler” type condensation of o-aminobenzylpyrrole ( 6 ) and methyl glyoxylate or the methoxy hemiacetal thereof.