Saturday Night Synthesis: Prazosin
Of course, if you don't live in Europe, the title will lose all its sense but, come on, use some imagination!
This is the first synthesis here, and I opted for an important drug, Prazosin, mainly used in the treatment of hypertension: an alpha-1-adrenergic antagonist.
This molecule is the lead for other quinazoline derivatives such as doxazosin and cyclazosin.
Here is the synthesis:
This is not totally synthetic, so, if you know a more sophisticated version of this synthesis, please, I'd love to know where I can find it. (I mean, I'm still an undergrad).
For what concerns this synthesis, it's certainly not a complicated one. The very first step involves sodium cyanate and yields a product which can remind of a ketene.
Phosphoroxidchloride is used as chlorinating agent.
I'd like to point out that it's due to thermodynamic reasons that we substitute one Cl only (how lucky, eh?)
The most interesting aspect is the way we yield the furanyl-piperazinyl-methanone. We set pH at 5.5, because the two NH groups in the piperazine have different basicity and this, plus the great reactivity of the furan-2-carbonyl chloride, would lead to double substituted products (hence, a mixture of three products). Thanks to this particular pH, you may say, we protect one of the NH functions and we increase selectivity.
