Disopyramide Ethanol

Nitrilopyramine is heated with concentrated sulfuric acid for 4 hours on a steam bath, the mixture is poured into ice after which it is made alkaline with 10 normal sodium hydroxide. The pH of the solution is then adjusted to 6 with acetic acid and the solution is washed with toluene. The mixture is again made alkaline with 10 normal sodium hydroxide and extracted with toluene. The toluene is evaporated and the residue dissolved in ethanol and treated with activated carbon. The ethanol is then evaporated and the residue recrystallized from hexane to give disopyramide. The phosphoric acid salt of disopyramide is prepared by reacting disopyramide with a phosphoric acid solution.1 The synthesis pathway is illustrated in Figure 1. 

Fig. 3 Chromatograms showing analysis of disopyr-amide and mono-A -dealkyldisopyramide enantiomers in plasma (A) blank plasma, (B) plasma spiked with 625 ng/ml of disopyramide and mono-A-dealkyldiso-pyramide enantiomers, (C) plasma sample from a healthy volunteer collected 6 hr after administration of 100 mg of Dicorantil. Peak assignments 1, (5)-(+)-disopyramide 2, )-disopyramide 3,4, metoprolol 5, (5 )-(+)-mono-iV -dealkyldisopyramide and 6, (/ )-(—)-mono-A-dealkyldisopyramide. Chromatographic conditions Chiralpak AD column (250 x 4.6 mm I.D., 10 pm particle size) hexane-ethanol (91 9, v/v) mobile phase plus 0.1% diethylamine 1.2ml/min flow rate and detection at 270 nm. (From Ref 1)...

Olsen H, Bredesen JE, Lunde PKM. Effect of ethanol intake on disopyramide elimination by healtl volunteers. EurJ Clin Pharmacol (1983) 25, 103-5. 

---