Evaluation and rapid scale-up of the synthesis of the pyrrolopyrimidines U-101033E and U-104067F

Large quantities of pure bulk drug were required to initiate development for possible indications as antiasthma and neuroprotective agents. Safety concerns and reproducibility problems encountered with the laboratory procedures (Bundy, G. L.; et al, J. Med, Chem, 1995, 38, 4161) forced the development of a reliable large-scale process which within six months produced > 100 kg of U-104067 free base in a single campaign, During the course of this work, procedures were also developed which allowed for the bulk preparation of analytically pure, pharmaceutically acceptable salt forms of both of the title compounds.