反应详情

温度

50 °C

A solution of Intermediate 74k (76 mg, 0.088 mmol) in THF (0.44 mL) was treated with tetrabutylammonium fluoride (1M in THF, 0.44 mL, 0.44 mmol) and the mixture was heated to 50° C. for 5 h. The mixture was evaporated in vacuo and the residue was partitioned between DCM and a saturated aqueous sodium bicarbonate solution. The layers were separated and the aqueous layer was then extracted with DCM (2×). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by FCC, using 0-9% [2M NH3 in MeOH] in DCM. Further purification by HPLC in 3 portions (Method 6, 30-60% MeCN in H2O, 0.1% HCO2H over 25 min) gave a colourless glass that was triturated with ether. The solid was collected by filtration, washed with ether and dried at 50° C. in vacuo to give the title compound (20 mg, 32%). LCMS (Method 5): Rt 3.47 min, m/z 710.5 [MH+]. 1H NMR (400 MHz, d6-DMSO): 0.91 (3H, d, J=6.3 Hz), 1.25 (9H, s), 1.44-1.57 (2H, m), 1.61-1.74 (2H, m), 1.74-1.92 (3H, m), 1.92-2.02 (1H, m), 2.01-2.16 (2H, m), 2.18 (6H, s), 2.68 (2H, t, J=6.8 Hz), 2.87-2.95 (1H, m), 3.16 (1H, dt, J=12.0, 4.1 Hz, partially obscured by water), 3.27-3.36 (11, m, obscured by water), 4.16 (2H, t, J=7.0 Hz), 4.31 (2H, s), 4.80-4.88 (1H, m), 4.92-5.11 (0.3H, br s), 5.53 (1H, t, J=4.3 Hz), 6.30 (1H, s), 7.14-7.22 (2H, m), 7.25-7.40 (41H, m), 7.64 (1H, d, J=10.0 Hz), 7.70 (1H, d, J=1.6 Hz), 8.00 (1H, s), 8.07 (1H, s), 8.19 (1H, s).

1. customThe mixture was evaporated in vacuo
2. customthe residue was partitioned between DCM
3. customThe layers were separated
4. extractionthe aqueous layer was then extracted with DCM (2×)
5. washThe combined organic layers were washed with brine
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. customevaporated in vacuo
9. customThe residue was purified by FCC
10. customFurther purification by HPLC in 3 portions (Method 6, 30-60% MeCN in H2O, 0.1% HCO2H over 25 min)
11. customgave a colourless glass that
12. customwas triturated with ether
13. filtrationThe solid was collected by filtration
14. washwashed with ether
15. customdried at 50° C. in vacuo