反应详情

A mixture of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((3-(but-3-en-1-yl)benzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (50 mg, 0.081 mmol) and Grubbs II catalyst (6.86 mg, 8.08 μmol) in DCM (50 mL) was refluxed for 2 h. It was then concentrated and the residue was dissolved in MeOH (3 mL). NaBH4 (15.28 mg, 0.404 mmol) was added and the reaction mixture was stirred at rt for 1 h. It was then quenched with water, extracted with EtOAc. The organic layer was dried over MgSO4, filtered and concentrated. The residue was then purified by biotage, eluting with 25% EtOAc/hexane to isolate ethyl (2S)-2-(tert-butoxy)-2-{4,24-dimethyl-11,23-dioxa-1,5,7,8-tetraazapentacyclo[22.2.2.16,9.113,17.02,7]triaconta-2,4,6(30),8,13(29),14,16-heptaen-3-yl}acetate (20 mg, 0.034 mmol, 41.8% yield) as a white solid. LCMS (M+1)=593.4. 1H NMR (400 MHz, CDCl3) δ 7.36-7.32 (m, 2H), 7.23-7.16 (m, 2H), 6.61 (s, 1H), 5.93 (s, 1H), 4.66 (s, 2H), 4.61-4.52 (m, 2H), 4.34 (td, J=12.3, 2.2 Hz, 1H), 4.27-4.16 (m, 2H), 3.85 (td, J=12.0, 2.2 Hz, 1H), 3.42-3.36 (m, 2H), 3.17 (d, J=11.7 Hz, 1H), 2.81 (dt, J=13.1, 6.3 Hz, 2H), 2.65-2.60 (m, 4H), 2.00 (dd, J=13.7, 2.2 Hz, 1H), 1.89 (dd, J=13.6, 2.1 Hz, 1H), 1.85-1.70 (m, 4H), 1.61-1.43 (m, 4H), 1.26-1.21 (m, 15H).

1. temperaturewas refluxed for 2 h
2. concentrationIt was then concentrated
3. dissolutionthe residue was dissolved in MeOH (3 mL)
4. customIt was then quenched with water
5. extractionextracted with EtOAc
6. dry with materialThe organic layer was dried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was then purified by biotage
10. washeluting with 25% EtOAc/hexane