Sodium Carbonate → HCID 25121259, compound

Participants

Reaction Conditions

Reaction Steps

Combine 5-(bromomethyl)-2-fluoro-4-iodopyridine (0.2 g, 0.63 mmol), piperidin-4-ol (0.192 mg, 1.9 mmol), and diisopropylethylamine (0.22 mL, 1.27 mmol) in acetonitrile (3.0 mL). Heat the reaction mixture at 80° C. for 2 h and cool to RT. Remove the organic solvent to give crude 1-((6-fluoro-4-iodopyridin-3-yl)methyl)piperidin-4-ol. Combine crude 1-((6-fluoro-4-iodopyridin-3-yl)methyl)piperidin-4-ol (0.63 mmol), N-(2-(1H-1,2,3-triazol-1-yl)ethyl)-5-fluoro-4-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[b]thiophen-2-yl)pyrimidin-2-amine (0.15 g, 0.32 mmol, sodium carbonate (0.102 g, 0.96 mmol), 2-(di-tert-butylphospho)biphenyl (0.006 g, 0.06 mmol) and Pd(dppf)Cl2 (0.026 g, 0.1 mmol) in THF (3 mL) and water (1 mL). Heat the mixture at 120° C. for 10 min in a microwave reactor. Pour the crude reaction mixture onto a strong cation exchange (SCX) (10 g) column. Elute the desired product with 2 N methanolic ammonia (40 mL) and concentrate. Purify by reverse phase chromatography (28% isocratic at 85 mL/min for 8 min on a 30×75 mm, 5 mm, C18 ODB MS XBridge™ column, Solvent A: water with 0.01 M ammonium bicarbonate, Solvent B: acetonitrile) to afford the title compound (91 mg, 52%). MS (ES) m/z 549 [M+1]+.

Provenance & Evidence