反应详情

A solution of (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one (50 mg, 0.104 mmol), 2-(6-chloropyridazin-3-yl)-propan-2-ol (20 mg, 0.151 mmol), Pd(PPh3)2Cl2 (30 mg, 0.046 mmol), 2 M aq Cs2CO3 (0.4 mL) in dioxane (5 mL) was heated at reflux for 2 h. The reaction mixture was concentrated, and the residue was treated with water (20 mL) and extracted with EtOAc (3×10 mL). The combined organic layer was washed with satd aq NaCl solution, dried with anhydrous Na2SO4, and concentrated to give an oil, which was purified by preparative TLC and HPLC to give the product. LC-MS Method 2 tR=1.031 min, m/z=490.3; 1H NMR (CD3OD): δ0.89 (s, 1H), 0.96 (s, 3H), 1.28 (m, 6H), 1.57 (d, 3H), 1.66 (m, 6H), 2.15 (s, 2H), 2.28 (m, 1H), 2.56 (m, 2H), 3.08 (m, 1H), 5.62 (m, 1H), 7.13 (d, 2H), 7.38 (m, 5H), 7.82 (m, 2H), 8.05 (m, 2H).

1. temperatureat reflux for 2 h
2. concentrationThe reaction mixture was concentrated
3. additionthe residue was treated with water (20 mL)
4. extractionextracted with EtOAc (3×10 mL)
5. washThe combined organic layer was washed with satd aq NaCl solution
6. dry with materialdried with anhydrous Na2SO4
7. concentrationconcentrated
8. customto give an oil, which
9. customwas purified by preparative TLC and HPLC
10. customto give the product