Phenyl 6-(((tert-butyldimethylsilyl)oxy)methyl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate (intermediate 38, 105 mg, 0.222 mmol) and 6-amino-4-(oxetan-2-ylmethoxy)nicotinonitrile (intermediate 34A, 54.7 mg, 0.267 mmol) were dissolved in THF (2 ml) under argon. The resulting solution was cooled to −78° C. and treated slowly with LHMDS (1 M in THF, 0.489 ml, 0.498 mmol). The reaction mixture was stirred at −78° C. for 45 min and then slowly warmed up to room temperature. The reaction mixture was poured into sat. aq. NH4Cl and extracted twice with DCM. The organic phase was then dried over Na2SO4, filtered and evaporated. The crude material was purified by preparative supercritical fluid chromatography (SFC 1, NH2 column). The 6-(((tert-butyldimethylsilyl)oxy)methyl)-N-(5-cyano-4-(oxetan-2-ylmethoxy)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide containing fractions were concentrated and then dissolved in THF (2 ml) and water (2 ml) and treated with conc. HCl (0.39 ml). The reaction mixture was stirred 16 h at room temperature. The reaction mixture was quenched with aq. sat. NaHCO3 and extracted 3× with DCM. The org layer was dried over Na2SO4, filtered and concentrated under vacuum. The crude material was treated with a small quantity of DCM and then the product was precipitated by addition of heptanes. The solid was collected by centrifugation and dried under vacuum to obtain the title compound as a white solid.
