Synthesis of Pyrimidoquinolines via the Pictet-Spengler Reaction

Significance

Reported is the first use of a pyri­midine ring as the π-nucleophilic component in the Pictet-Spengler reaction. The starting materials, 2-amino-4-substituted pyrimidines, or 2-amino-4,6-disubstituted pyrimidines were prepared via a 2-4-step sequence starting from 3-dimethyl-amino-1-(2-nitrophenyl)-propenone. The Pictet-Spengler reaction proceeds in moderate to good yields, tolerating EWGs and EDGs on the aldehyde reactant. 4,6-Disubstituted pyrimidines afforded slightly lower yields than 4-monosubstituted analogues, failing in two cases of 2-substituted aryl aldehydes which may be due to a steric R^²,R^³ effect. Attempted reaction with a pyridine subunit instead of a pyrimidine failed.