反应详情

温度

85 °C

A mixture of tert-butyl (1R,2S)-2-(4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate (60 mg, 0.109 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (34 mg, 0.164 mmol) and bis(triphenylphosphine)palladium chloride (15 mg, 0.022 mmol) in DME (1 mL) was placed in a vial. The vial was purged with nitrogen and aqueous sodium carbonate (2 N, 0.219 mL, 0.437 mmol) was added. The vial was sealed and the reaction mixture heated in an oil bath at 85° C. for 3 h. The reaction mixture was filtered through a pad of Celite, which was rinsed with MeOH and DCM. The solvent was removed in vacuo and the residue was diluted with DMSO and MeOH (1/1). The resulting mixture was filtered to recover a white precipitate (31.3 mg). The mother liquor was purified via preparative HPLC. The fractions were collected and dried in vacuo to recover an additional white solid (10.2 mg). The two crops were combined to give the title compound as a white solid (41.5 mg, 64%). [M+H] calc'd for C31H39FN6O5, 595; found, 595.

1. additionwas added
2. customThe vial was sealed
3. filtrationThe reaction mixture was filtered through a pad of Celite, which
4. washwas rinsed with MeOH and DCM
5. customThe solvent was removed in vacuo
6. additionthe residue was diluted with DMSO and MeOH (1/1)
7. filtrationThe resulting mixture was filtered
8. customto recover a white precipitate (31.3 mg)
9. customThe mother liquor was purified via preparative HPLC
10. customThe fractions were collected
11. customdried in vacuo
12. customto recover an additional white solid (10.2 mg)