Diisopropylamine → {1-benzenesulfonyl-2-[1-hydroxy-2-(tetrahydro-pyran-4-yl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a suspension of (1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-carbamic acid tert-butyl ester (prepared as in Example 107, 3.4 g, 9.1 mmol) in dry tetrahydrofuran (120 mL) at −78° C. was added freshly prepared lithium diisopropylamide [prepared by adding 1.6 M n-butyllithium in n-hexane (17.1 mL, 27.3 mmol) to a 0° C. solution of diisopropylamine (2.76 g, 27.3 mmol) in dry tetrahydrofuran (20 mL)] dropwise. The mixture was stirred at −78° C. for 5 min and then treated with (tetrahydro-pyran-4-yl)-acetaldehyde (2.91 g, 22.75 mmol) dropwise. The resulting mixture was stirred at −78° C. for 1 h and quenched with brine. The mixture was extracted with ethyl acetate (2×100 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by flash column chromatography (QingDao silica gel, 200-300 mesh, 75% ethyl acetate/hexanes) afforded {1-benzenesulfonyl-2-[1-hydroxy-2-(tetrahydro-pyran-4-yl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-carbamic acid tert-butyl ester (1.5 g, 33%) as a white solid: LC/MS m/e calcd for C25H31N3O6S [M+H]+ 502.61, observed 502.2.

Provenance & Evidence