1-Aminopyridinium salts pyrazolo pyridine

The chemistry used in the preparation of pyrazolo[ 1,5-a]pyridines is influenced by the presence of the bridgehead nitrogen. Syntheses involve the almost exclusive use of /V-aminopyridinium salts and often require the generation of ylides. 

Treatment of 2-alkyl- or 2-hydroxymethyl-l-aminopyridinium salts with acyl or aroyl chlorides in the presence of base causes cyclization to pyrazolo[l,5-a]pyridine derivatives. If the 3-position is unsubstituted, acylation occurs at this position under the reaction conditions (Eq. 13).18141 There is good evidence that the initial step is acylation of the iV-amino group. This reaction has been extended to the synthesis of various bridgehead nitrogen heterocyclic systems including pyrazolodiazines (11),9 pyrazolo[5,l- ]thiazole (12),142 and imidazo[l,2-h]pyrazole (13).142... 

Pyrazolo[l,2-d]pyridine derivatives (138) are prepared by acylation of 2-methyl-l-aminopyridinium salts (137) (68JOC3766) the starting materials are obtained by amination of 2-methylpyridines (136) with hydroxlyamine-O-sulfonic acid (59CB2521) (Scheme 30). 

Salts of 3-[3-(phenylpropynoyloxy)propyl]-N-aminopyridinium (43) (Equation (5)) undergo dipolar addition to form tricyclic pyrazolo[l,5-a]pyridines (44) <83H(20)20i, 85JSC(P1)379>. N-Methoxycarbonylmethyl-3-[3-(phenylpropynoyloxy)propy]pyridinium salts undergo a similar dipolar addition to give indolizine derivatives. 

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