反应详情

To a solution of {5-[4-(tert-Butyl-diphenyl-silanyloxy)-piperidin-1-yl]-imidazo[4,5-b]pyridin-3-ylmethyl}-dimethyl-amine (574 mg, 1.12 mmol) and 4-(2-cyano-5-methoxycarbonyl-phenyl)-pyrrolo[2,3-c]pyridine-1-carboxylic acid tert-butyl ester (474 mg, 1.26 mmol, 1.1 eq) (Step 1 example 140) in THF (0.1M), cooled to −78° C., was slowly added 1M LDA (2 mol eq). After 1 hr, the reaction mixture was quenched with 50% acetic acid in water (0.25 vols.) at −78° C. The mixture was allowed to warm to room temperature and concentrated to remove most THF. The residue was diluted with EtOAc (20 mL) and basified with aqueous ammonium hydroxide (30%) until pH>8. The organic layer was washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was then purified by trituration from Acetonitrile affording 4-(5-{5-[4-(tert-Butyl-diphenyl-silanyloxy)-piperidin-1-yl]-3H-imidazo[4,5-b]pyridine-2-carbonyl}-2-cyano-phenyl)-pyrrolo[2,3-c]pyridine-1-carboxylic acid tert-butyl ester as a red solid (900 mg, 1.01 mmol, 90%). MS ESI m/z 802.7 (M+H)+.

1. customthe reaction mixture was quenched with 50% acetic acid in water (0.25 vols.) at −78° C
2. concentrationconcentrated
3. customto remove most THF
4. additionThe residue was diluted with EtOAc (20 mL)
5. washThe organic layer was washed with brine
6. dry with materialdried (MgSO4)
7. concentrationconcentrated in vacuo
8. customThe residue was then purified by trituration from Acetonitrile