反应详情

To a solution of tert-butyl (2S)-2-isobutyl-4-[2-(1-tritylpyrazolo[5,4-b]pyridin-3-yl)thiazol-4-yl]piperazine-1-carboxylate (149 mg, 0.2176 mmol) and triethylsilane (101.2 mg, 139.0 μL, 0.8704 mmol) in DCM (2 mL) at 0° C. was added TFA (0.3 mL,). Then ice-bath removed and mixture stirred at room temperature for 1 h. Added more TFA (0.3 mL) and stirred for a further 1 h. Basified with minimal sat. NaHCO3 and extracted with EtOAc. Organics combined, washed with small amount of water, brine, dried (MgSO4), filtered and concentrated in vacuo. Crude product purified by flash chromatography (12 g SiO2, 0 to 6% MeOH (containing 10% ammonium hydroxide)/DCM) to leave product as a pale green solid after freeze-drying (MeCN/H2O) (18.18 mg, 24%); 1H NMR DMSO-d6 δ 0.87-0.86 (br m, 1H), 0.92 (dd, 6H), 1.31-1.20 (m, 2H), 1.85-1.76 (m, 1H), 2.36 (t, 1H), 2.71 (td, 1H), 2.87-2.78 (m, 2H), 3.00 (d, 1H), 3.80 (dd, 2H), 6.30 (s, 1H), 7.37 (dd, 1H), 8.64 (m, 2H); ES+ 343.08.

1. customThen ice-bath removed
2. additionAdded more TFA (0.3 mL)
3. stirringstirred for a further 1 h
4. extractionextracted with EtOAc
5. washwashed with small amount of water, brine
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customCrude product purified by flash chromatography (12 g SiO2, 0 to 6% MeOH (containing 10% ammonium hydroxide)/DCM)
10. customto leave product as a pale green solid
11. dry with materialafter freeze-drying (MeCN/H2O) (18.18 mg, 24%)