反应详情

温度

90 °C

A resealable tube was charged with (S)-1′-bromo-2′-((3-methyloxetan-3-yl)methoxy)-7′-(pyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine (300 mg, 0.590 mmol), 2-methyl-3-butyn-2-ol (248 mg, 2.95 mmol), tetrakis(triphenylphosphine)palladium (68.2 mg, 0.059 mmol) and copper(i) iodide (22.48 mg, 0.118 mmol). To this were added DMF (1180 μL, 0.590 mmol) and diisopropylamine (1241 μL, 8.85 mmol). The reaction was flushed with argon, sealed and heated at 90° C. for 1.5 hours. The reaction was diluted with water (100 mL) and poured into a separatory funnel containing EtOAc (50 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (3×25 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to provide a brown oil that was purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (40 g), 0-100% CH2Cl2 to 10:1 methanol in methylenechloride with 0.1% ammonium hydroxide) to provide (S)-4-(2-amino-2′-((3-methyloxetan-3-yl)methoxy)-7′-(pyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthene]-1′-yl)-2-methylbut-3-yn-2-ol as a light yellow solid. MS m/z=512.2 [M+H].

1. customThe reaction was flushed with argon
2. customsealed
3. additionThe reaction was diluted with water (100 mL)
4. additionpoured into a separatory funnel
5. additioncontaining EtOAc (50 mL)
6. customThe layers were separated
7. extractionthe aqueous layer was extracted with ethyl acetate (3×25 mL)
8. washThe combined organic layers were washed with brine
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customto provide a brown oil that
13. customwas purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (40 g), 0-100% CH2Cl2 to 10:1 methanol in methylenechloride with 0.1% ammonium hydroxide)