The Mannich reaction of 1-(3-amino)-and (3-amino-4-methoxy) benzyl-6, 7-dimethoxy-1, 2, 3, 4-tetrahydroisoquinolines (Va and Vb) with 36% formaldehyde solution in ethanol without acid afforded aminoprotoberberines (VIa and VIb), formed by cyclization at the position para to the amino group.
