反应详情

A vial was charged with (S)-1′-bromo-2′-(neopentyloxy)-7′-(pyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine (68.1 mg, 0.138 mmol), dicyanozinc (81 mg, 0.689 mmol), tetrakis(triphenylphosphine)palladium(0) (31.8 mg, 0.028 mmol), and DMF (689 μL). The vial was sealed and placed in a 120° C. oil bath for 12 hours. The mixture was diluted with water and extracted with DCM (3×). The combined organic extracts were dried over sodium sulfate, filtered, and evaporated. The residue was chromatographed on a 25-g SNAP column, eluting with a 90:10:1 mix of DCM/MeOH/NH4OH in DCM. This gave ca. 40 mg of a white powder that was impure by HPLC. The solid was combined with 104487-6-2 in DMSO/MeOH and purified by reverse-phase HPLC (10-90% CH3CN/H2O with 0.1% TFA). The fractions containing product were combined in saturated aq. sodium bicarbonate solution with the aid of methanol and extracted with DCM (3×). The combined organic extracts were dried over sodium sulfate, filtered, and evaporated to give (S)-2-amino-2′-(neopentyloxy)-7′-(pyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthene]-1′-carbonitrile as an off-white powder after evaporation from DCM/hexane.

1. customThe vial was sealed
2. customplaced in a 120° C.
3. customfor 12 hours
4. extractionextracted with DCM (3×)
5. dry with materialThe combined organic extracts were dried over sodium sulfate
6. filtrationfiltered
7. customevaporated
8. customThe residue was chromatographed on a 25-g SNAP column
9. washeluting with a 90:10:1
10. additionmix of DCM/MeOH/NH4OH in DCM
11. custompurified by reverse-phase HPLC (10-90% CH3CN/H2O with 0.1% TFA)
12. additionThe fractions containing product
13. extractionextracted with DCM (3×)
14. dry with materialThe combined organic extracts were dried over sodium sulfate
15. filtrationfiltered
16. customevaporated