Sodium Hydroxide → HCID 78322881, compound

Participants

Reaction Steps

9-Borabicyclo[3.3.1]nonane dimer (0.431 g) was added to a solution of (S)-tert-butyl (1-(4-amino-6-bromo-5-(quinolin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)but-3-en-2-yl)carbamate (0.3 g) obtained in Reference Example 1 in tetrahydrofuran (4.5 ml) under a nitrogen atmosphere at room temperature, and the mixture was stirred at room temperature for 2 hours. A 4 N sodium hydroxide aqueous solution (2.12 ml) was slowly added to the reaction mixture at room temperature, and degassed under reduced pressure. Under a nitrogen atmosphere, (tetrakistriphenylphosphine)palladium(0) (0.136 g) was added to the resulting mixture, and stirred at 64° C. for 12 hours. After the reaction mixture was cooled, and diluted with ethyl acetate, a saturated ammonium chloride aqueous solution was added thereto. After the insoluble matter resulting in this stage was removed by filtration, the organic layer was separated. The resulting organic layer was dried over anhydrous sodium sulfate, then filtered, and concentrated under reduced pressure to obtain a crude product. The crude product was purified by silica gel column chromatography (developing solvent: ethyl acetate/methanol) to obtain (S)-tert-butyl (4-amino-5-(quinolin-3-yl)-6,7,8,9-tetrahydropyrimido[5,4-b]indolizin-8-yl)carbamate (203 mg) (yield: 80%) as a light-yellow solid.

Provenance & Evidence