Phosphorus oxychloride → 1-Chloro-7-nitro-3,4-dihydroisoquinoline

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Reaction Steps

Tricyclic heterocycles can be prepared by the process outlined in Scheme 7. 7-Nitro-3,4-dihydro-2H-isoquinolin-1-one 23 is heated in POCl3 at a temperature above RT, preferably at a temperature sufficient for reflux, to form the 1-chloro-7-nitro-3,4-dihydroisoquinoline 24. The 1-chloro-7-nitro-3,4-dihydroisoquinoline 24 is dissolved in a solvent, such as THF, and H2NNH2 is added. The reaction is heated with HC(OEt)3 at a temperature above RT, preferably at a temperature above about 75° C., and more preferably at a temperature at about 115° C. to give the nitro-substituted tricyclic. Hydrogenation, such as with an H2 atmosphere in the presence of a catalyst, such as Pd/C, gives 2-amino-5,6,7-trihydro-1,2,4-triazolo[3,4-a]isoquinoline 25.

Provenance & Evidence