Chlorotrimethylsilane-promoted one-pot synthesis of steroidal[17,16-d]pyrimidines

A novel and practical procedure was developed for the preparation of steroidal[17,16-d]pyrimidines by chlorotrimethylsilane (TMSCl)-promoted one-pot multicomponent Biginelli-like condensations of steroid-17-ones, urea and aromatic aldehydes. First, treatment of the steroid-17-ones with urea and aromatic aldehydes in dimethylformamide (DMF)/acetonitrile (ACN) gives the corresponding Biginelli products, following the aromatising reaction of the Biginelli products at the same time under air to yield the desired steroidal[17,16-d]pyrimidines (78-88%). Since steroidal[17,16-d]pyrimidines with hydroxyl group can be subsequently converted into steroidal[17,16-d]pyrimidine derivatives, this general method provides a highly efficient route to these biologically important compounds.