NEW SYNTHETIC STEPS FOR THE METHOD OF PREPARING THE PDE4B INHIBITOR 1-({(5R)-2-[4-(5-CHLOROPYRIMIDINI-2-YL)PIPERIDIN-1-YL]-5-OXIDO-6,7-DIHYDROTHIENE[3,2-D]PYRIMIDINI-4-YL}AMINO)CYCLOBUTYL]METHANOL

Abstract

The present invention relates to a method for preparing Intermediate VIII, wherein in step a) 5-Chloro-2-iodopyrimidine and boronic ester Boc V are reacted in the presence of bis(amphos)palladium-II chloride catalyst to give Intermediate VI, and wherein in step b) Intermediate VI is hydrogenated to give the unisolated Intermediate VII, and wherein in step c) the unisolated Intermediate VII is reacted with hydrochloric acid to give Intermediate VIII. The invention also relates to methods for preparing the other intermediates which, when interacting with Intermediate VIII, will give the PDE4B inhibitor of formula XX in its crystalline form B. The PDE4B inhibitor of formula XX exhibited, in Phase II clinical data, a reduction in the rate of decline in lung function in patients with idiopathic pulmonary fibrosis (IPF) after 12 weeks of treatment.