6-broMo-4-Methoxypyrazolo[1,5-a]pyridine

1207557-35-4

1207557-36-5

Step B: Decarboxylation Ethyl 6-bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carboxylate (15, 5.2 g, 18.24 mmol) was dissolved in hydrobromic acid (100 mL, 884 mmol), and the reaction was heated to 100 °C for 1 hour. After completion of the reaction, the mixture was cooled to 0 °C and neutralized with 1 M sodium hydroxide solution (182 mL, 912 mmol). The reaction mixture was diluted with ethyl acetate and washed sequentially with 1 N aqueous sodium hydroxide solution and saturated brine, and the organic phase was dried with anhydrous sodium sulfate. After filtration and concentration, the residue was purified by column chromatography (eluent: 0-35% hexane solution of ethyl acetate, linear gradient) to afford 6-bromo-4-methoxypyrazolo[1,5-a]pyridine (16, 2.475 g, 10.90 mmol, 60% yield). Mass spectrum (APCI): m/z 228.1 [M+H]+. Scheme 2: Molecules of type 21 were prepared according to Scheme 2. O- homotrimethylbenzenesulfonyl hydroxylamine (1) was used to prepare N-imino-pyridinium-based methanesulfonate 14, which was used to obtain pyrazolopyridine 15 via [3+2] cycloaddition reaction with ethyl propargylate. decarboxylation in pure hydrobromic acid gave 16. 6-position functionalization of the pyrazolopyridine nucleus was accomplished via a Suzuki coupling reaction to introduce aryl or heteroaryl functional groups (17), see WO 2004052286 A2 and WO 2007085873 A1 for specific borate ester examples. halogenation by reaction with N-iodosuccinimide gave the iodide 18, which was followed by a second Suzuki coupling with the thioborate ester to give the coupling product 19. hydrolysis of the ester yielded the acid 20, which was finally coupled with an amine to give the target compound 21 .