Dofetilide ,synthesis

Dodecylphenol (PDDP), 2 222—223 health and safety data, 2 220t physical properties of, 2 205t Dodecylsuccinic anhydride (DDSA), 10 406 Doebner-von Miller synthesis, 2 787 DOE Pro XL 3.0, features compared to other software, 8 398t Dofetilide, 5 102, 104, 106... 

The synthesis of dofetilide, a drug to combat erratic heartbeat... 

The chapter ends with a complete synthesis of an important new drug. Cardiac arrhythmia (erratic and inefficient heart action) is a major problem in the modern world causing poor lifestyle (exhaustion) and death by blood clots. A new drug dofetilide (Tikosyn ) is being introduced by Pfizer to treat this problem. It works by blocking the passage of potassium ions out of heart muscle and so delays the onset of an irregular beat until the next normal beat takes over. 

We are going to do a little more than simply give the reactions that eventually made up the synthesis of dofetilide. We are going to put ourselves in the place of the chemists who invented the synthesis and try to see what led them to the reactions they chose. First, we should inspect the structure of the molecule. There are two sulfonamides, one at each end. We have seen how to make sulfonamides earlier in this chapter when saccharin was being discussed. The usual way is to react the amine with a sulfonyl chloride. In this case we shall need to react methane sulfonyl chloride (MeS02Cl or MsCl) with the aromatic amines. This is a well-known reaction and should work well here. The other functional groups—tertiary amine and alkyl aryl ether—should not interfere so no protection is needed. 

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