N-Heterocyclic Derivatives as NOS Inhibitors

Davey etal, US Patent 6,525,051 (February 25, 2003) Assignee Schering Aktiengesellschaft 

UtOity Nitric Oxide Synthase Inhibitors for Treatment of Inflammation 

To 250ml ethyl alcohol was added 5-(amidino)methyl-l,3-benzodioxolane (0.23 mol), 50 ml diethyl methylmalonate, 125 ml 25% NaOH in methyl alcohol, and the mixture refluxed 5 hours. The solvent was removed, the residue dissolved in water, acidified with 6 M HCl, and the product isolated by precipitation. 

To the product from Step 1 (54 g) dissolved in 65 ml N,N-dimethylaniline was added 300 ml phosphorous oxychloride and the mixture heated 3 hours at 45 °C. The mixture was cooled, the solvent removed, and the residue added to ice water. The solids were collected, dissolved in CH2CI2, washed with K2CO3 solution, re-crystallized in hexane, and the product isolated. 

3-Benzodioxol-5-yl)methyl]-6-chloro-4[4-(lH-imidazol-l-yl)phenoxy]-5-methylpyrimidine 

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