Dimethylformamide → 2-(Phenoxy)-3-dimethylamino-propenal

Beteiligte Stoffe

Reaktionsschritte

An appropriate phenol or substituted phenol (i.e., a compound suitable for forming the Y2 substituent of formula I) is reacted with a molar excess of chloroacetaldehyde diethyl acetal (ClCH2CH(OCH2CH3)2) in the presence of potassium hydroxide to form a phenoxyacetaldehyde diethyl acetal. This procedure is taught by Lipinski et al., J. Med. Chem., 23, 1026 (1980) which is incorporated herein by reference. The phenoxyacetaldehyde diethyl acetal is then added to a mixture containing POCl3 and DMF and heated for a period of time sufficient to form 2-(phenoxy)-3-dimethylamino-propenal which is then reacted with malonamide (i.e., CH2 (CONH2)2) in the presence of t-BuOK and DMSO. The desired, 5-(phenoxy-2-hydroxy-3-pyridinecarboxamide may then be collected by conventional techniques. The isolated pyridinecarboxamide is then added to phenylphosphonic dichloride followed by the addition of PCl5. The mixture is heated and the desired 5-(phenoxy)-2-chloro-3-pyridinecarbonitrile is isolated. This product may then be treated with the desired alkylmercaptan in NaOH to form the 5-(phenoxy)-2-(R-thio)- 3-pyridinecarbonitrile which may then be oxidized to the R-sulfinyl or R-sulfonyl form and/or to the 3-pyridinecarboxamide compound if desired.

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