反应详情

To a solution of ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (32 g, 58.9 mmol) in dry DCM (500 mL) was added Dess-Martin periodinane (24.97 g, 58.9 mmol). The resulting bright orange-red solution was stirred for 90 min. The reaction was quenched by stirring with a saturated solution of Na2S2O3 (100 mL) and sat. NaHCO3 (100 mL) for 25 min to quench any unreacted Dess-Martin reagent. The reaction mixture was poured into a separatory funnel and organic layer separated. The aqueous layer was further extracted with EtOAc. The two organic components were separately washed with brine, then combined, dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was then purified via Biotage (5-40%) EtOAc/hexane to afford ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate (22.6 g, 41.7 mmol, 70.9% yield) as off-white solid. 1H NMR (500 MHz, CDCl3) δ 8.12 (t, J=1.7 Hz, 1H), 7.91 (dt, J=7.8, 1.3 Hz, 1H), 7.56 (ddd, J=8.0, 2.0, 0.9 Hz, 1H), 7.37 (t, J=7.9 Hz, 1H), 6.82 (s, 1H), 6.00 (ddt, J=17.2, 10.4, 5.2 Hz, 1H), 5.44-5.36 (m, 1H), 5.24-5.17 (m, 1H), 4.46-4.35 (m, 2H), 3.98 (dt, J=5.1, 1.5 Hz, 2H), 3.80-3.71 (m, 2H), 3.69-3.60 (m, 2H), 2.60 (s, 3H), 2.03-1.88 (m, 4H), 1.46-1.40 (m, 3H), 1.31 (s, 3H). LCMS (M+H)=543.3.

1. customThe reaction was quenched
2. stirringby stirring with a saturated solution of Na2S2O3 (100 mL) and sat. NaHCO3 (100 mL) for 25 min
3. customto quench any unreacted Dess-Martin reagent
4. additionThe reaction mixture was poured into a separatory funnel
5. customorganic layer separated
6. extractionThe aqueous layer was further extracted with EtOAc
7. washThe two organic components were separately washed with brine
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe residue was then purified via Biotage (5-40%) EtOAc/hexane