反应详情

To a solution of {6-[3-isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoylamino]-pyridin-3-yl}-methyl-phosphinic acid ethyl ester (469 mg, 0.960 mmol) in DCM (10 mL) was added HMDS (1.62 mL, 7.68 mmol) and TMSBr (0.51 mL, 3.84 mmol) at rt. Stirred at rt overnight. TMSI (0.07 mL, 0.480 mmol) was added to the milky mixture on the second day. Stirred at rt for 1.5 hr. The mixture was concentrated, re-dissolved in EtOAc (10 mL), and filtered through a 0.4 μm syringe filter to remove insoluble NH4Br. The filtrate was concentrated and the residue was dissolved in MeOH (10 mL), stirred at rt for 3 hr, and concentrated again. The resulting residue was partitioned between EtOAc and water. After layers were separated, the aqueous layer was extracted with EtOAc (2×). Combined EtOAc layers were washed with brine (1×), dried with anhydrous MgSO4, filtered, and concentrated to give {6-[3-Isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoylamino]-pyridin-3-yl}-methylphosphinic acid (242 mg, 53%) as a yellow foam. 1H NMR (300 MHz, DMSO-d6): δ 11.08 (br, 1H), 8.68 (ddd, J=6, 2, 1 Hz, 1H), 8.32 (m, 1H), 8.14 (m, 1H), 7.51 (dd, J=5, 3 Hz, 1H), 7.36 (dd, J=3, 2 Hz, 1H), 7.24 (m, 1H), 7.20 (m, 1H), 7.15 (dd, J=5, 1 Hz, 1H), 6.71 (m, 1H), 4.77 (m, 1H), 4.28 (m, 2H). 3.11 (m, 2H), 1.58 (d, J=15 Hz, 3H), 1.30 (d, J=6 Hz, 6H); LC-MS (m/z): 461.3 [C23H25N2O5PS+H]+. Anal. Calcd. for (C23H25N2O5PS+1.1H2O): C, 55.02; H, 5.71; N, 5.83. Found: C, 55.02; H, 5.31; N, 5.44.

1. stirringStirred at rt for 1.5 hr
2. concentrationThe mixture was concentrated
3. dissolutionre-dissolved in EtOAc (10 mL)
4. filtrationfiltered through a 0.4 μm syringe
5. filtrationfilter
6. customto remove insoluble NH4Br
7. concentrationThe filtrate was concentrated
8. dissolutionthe residue was dissolved in MeOH (10 mL)
9. stirringstirred at rt for 3 hr
10. concentrationconcentrated again
11. customThe resulting residue was partitioned between EtOAc and water
12. customAfter layers were separated
13. extractionthe aqueous layer was extracted with EtOAc (2×)
14. washCombined EtOAc layers were washed with brine (1×)
15. dry with materialdried with anhydrous MgSO4
16. filtrationfiltered
17. concentrationconcentrated