反应详情

A 2-5 ml resealable tube was charged with 3-ethoxypyridin-2-amine (26.0 mg, 0.188 mmol), (S)-tert-butyl(7′-bromo-4′-fluoro-2′-methoxy-5,6-dihydrospiro[[1,3]thiazine-4,9′-xanthen]-2-yl)carbamate (80 mg, 0.157 mmol), Pd2 dba3 (15.82 mg, 0.017 mmol), t-BuXPhos (14.67 mg, 0.035 mmol) and sodium t-butoxide (33.2 mg, 0.346 mmol). Toluene (6280 was added, and the mixture was stirred for 2 min at RT, then was heated to 80° C. for 20 min. The reaction mixture was diluted with water and extracted with EtOAc. The organic extract was washed with saturated NaCl and dried over MgSO4. The solution was filtered and concentrated in vacuo to give the crude material as a orange oil. The crude material was purified by chromatography eluting with a gradient of 0% to 15% to 30% DCM/MeOH/NH4OH in DCM, to provide Boc-protected product as yellow solid. The Boc protected product was dissolved in 1 mL of DCM and 1 mL of TFA was added. The reaction mixture was stirred at rt for 40 mins. Then the solvent was reduced and crude product was purified by chromatography eluting with a gradient of 20% to 35% to 50% DCM/MeOH/NH4OH in (40% EtOAc in Heptane), to provide (S)—N7′-(3-ethoxypyridin-2-yl)-4′-fluoro-2′-methoxy-5,6-dihydrospiro[[1,3]thiazine-4,9′-xanthene]-2,7′-diamine (16 mg, 0.034 mmol, 21.84% yield) as light-yellow solid.

1. temperaturewas heated to 80° C. for 20 min
2. extractionextracted with EtOAc
3. extractionThe organic extract
4. washwas washed with saturated NaCl
5. dry with materialdried over MgSO4
6. filtrationThe solution was filtered
7. concentrationconcentrated in vacuo
8. customto give the crude material as a orange oil
9. customThe crude material was purified by chromatography
10. washeluting with a gradient of 0% to 15% to 30% DCM/MeOH/NH4OH in DCM
11. customto provide Boc-
12. stirringThe reaction mixture was stirred at rt for 40 mins
13. customcrude product was purified by chromatography
14. washeluting with a gradient of 20% to 35% to 50% DCM/MeOH/NH4OH in (40% EtOAc in Heptane)