121912-29-6

64-17-5

93913-86-1

121912-29-6

Example 2 Difluorotriacetate of [1-(pyridin-4-yl)piperidin-4-yl]methyl 2-[amino(imino)methyl]-1,2,3,4-tetrahydroisoquinoline-7-carboxylic acid; Step 1 Synthesis of ethyl 1-(pyridin-4-yl)piperidin-4- carboxylate; To a 1-(pyridin-4-yl)piperidin-4-carboxylic acid (20.0 g, 97.0 mmol) ethanol (480 mL) suspension of thionyl chloride (7.1 mL, 97.0 mmol) was added dropwise and the mixture was stirred at 50°C overnight. After completion of the reaction, the solvent was removed by evaporation under reduced pressure and the resulting residue was diluted with dichloromethane, washed sequentially with 1N aqueous sodium hydroxide and saturated aqueous ammonium chloride, the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford ethyl 1-(pyridin-4-yl)piperidine-4-carboxylate, which did not require further purification. Yield: 21.0 g (89.7 mmol, 93%). MS (ESI, m/z): 235 [M + H]+. 1H-NMR (CDCl3) δ: 1.26 (t, 3H), 1.72-1.86 (m, 2H), 1.97-2.05 (m, 2H), 2.49-2.58 (m, 1H), 2.93-3.02 (m , 2H), 3.82-3.02 (m, 2H). , 2H), 3.82 (dt, 2H), 4.16 (q, 2H), 6.66 (dd, 2H), 8.25 (dd, 2H).