Sodium Carbonate → (S)-2-amino-N-cyclopropyl-7'-(neopentyloxy)-5H-spiro[oxazole-4,9'-xanthene]-2'-carboxamide

Temperatur

170 °C

A 0.5-2 mL microwave vial charged with (R)-2′-bromo-7′-(neopentyloxy)-5H-spiro[oxazole-4,9′-xanthen]-2-amine (0.1000 g, 0.240 mmol), Mo(CO)6 (0.063 g, 0.240 mmol), acetoxy(2-(dio-tolylphosphino)benzyl)palladium (0.011 g, 0.012 mmol), sodium carbonate (0.025 g, 0.240 mmol), cyclopropylamine (0.025 mL, 0.359 mmol), and 1,4-dioxane (0.443 mL, 5.03 mmol) was sealed and heated to 170° C. for 30 minutes. The mixture was diluted with EtOAc and water and filtered through celite. The celite was washed with EtOAc and MeOH. The aqueous phase was extracted with EtOAc three times. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude was purified by silica gel chromatography (2-10% MeOH—CH2Cl2, then 10% MeOH—CH2Cl2). The product was purified again by reverse phase prep HPLC: 10-55% CH3CN (0.1% TFA)-water (0.1% TFA) in 26 min. The fractions were combined and neutralized with solid Na2CO3, extracted three times with DCM. The organic layer was concentrated to provide (S)-2-amino-N-cyclopropyl-7′-(neopentyloxy)-5H-spiro[oxazole-4,9′-xanthene]-2′-carboxamide.

1. customwas sealed
2. filtrationfiltered through celite
3. washThe celite was washed with EtOAc and MeOH
4. extractionThe aqueous phase was extracted with EtOAc three times
5. dry with materialThe organic layer was dried over Na2SO4
6. concentrationconcentrated in vacuo
7. customThe crude was purified by silica gel chromatography (2-10% MeOH—CH2Cl2
8. customThe product was purified again by reverse phase prep HPLC
9. extractionextracted three times with DCM
10. concentrationThe organic layer was concentrated

ORD-Eintrag

ord-b9e22da6ab2941209cb5efb8e3593f58

Quelldatensatz

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08883782B2