Trifluoroacetic acid → HCID 42625374, compound

Temperature

25 °C

A solution of the product from Example 22A (7.81 mmol) in dichloromethane (20 mL) was treated with trifluoroacetic acid (20 mL), and the mixture was stirred at 25° C. for 1 hour. The solvent was concentrated and the reaction was partitioned between ethyl acetate and 10% Na2CO3, and the organic phase was washed with brine and dried over MgSO4, filtered and concentrated. A solution of the residue (7.81 mmol) in THF (80 mL) was treated with the product from Example 1F (1.6 g, 8.47 mmol), DEPBT (3.5 g, 11.71 mmol), and N,N-diisopropylethylamine (6.8 mL, 39.04 mmol) and the mixture was stirred at 25° C. for 5 hours. The mixture was partitioned between ethyl acetate and 10% Na2CO3 solution. The organic phase was washed with additional 10% Na2CO3 solution and brine, dried over MgSO4, filtered and concentrated. The product was purified by chromatography on silica gel eluting with a gradient starting with 0-100% ethyl acetate/dichloromethane, followed by 0-10% methanol in ethyl acetate. The product was then purified by reversed phase chromatography on a C18 column eluting with a gradient starting with 5-100% acetonitrile in water (0.1% TFA). The product was, partitioned between ethyl acetate and 10% Na2CO3 solution. The organic phase was washed brine, dried over MgSO4, filtered and concentrated to give the title compound (1.32 g, 23% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.82 (s, 9 H), 0.91 (s, 9 H), 1.25 (m, 1 H), 1.51 (m, 2 H), 2.36 (m, 1 H), 2.46 (s, 3 H), 2.70 (m, 3 H), 2.96 (m, 1 H), 3.09 (m, 1 H), 3.23 (m, 1 H), 3.55 (s, 3 H), 3.65 (m, 1 H), 3.83 (d, J=9.93 Hz, 1 H), 4.14 (m, 3 H), 4.35 (m, 2 H), 4.50 (d, J=7.72 Hz, 1 H), 6.64 (d, J=9.93 Hz, 1 H), 7.09 (m, 12 H), 7.47 (d, J=9.19 Hz, 1 H), 7.71 (m, 2 H).

1. concentrationThe solvent was concentrated
2. customthe reaction was partitioned between ethyl acetate and 10% Na2CO3
3. washthe organic phase was washed with brine
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. stirringthe mixture was stirred at 25° C. for 5 hours
8. customThe mixture was partitioned between ethyl acetate and 10% Na2CO3 solution
9. washThe organic phase was washed with additional 10% Na2CO3 solution and brine
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated
13. customThe product was purified by chromatography on silica gel eluting with a gradient
14. customThe product was then purified by reversed phase chromatography on a C18 column
15. washeluting with a gradient
16. custompartitioned between ethyl acetate and 10% Na2CO3 solution
17. washThe organic phase was washed brine
18. dry with materialdried over MgSO4
19. filtrationfiltered
20. concentrationconcentrated

ORD record

ord-1a5ba03eb2fb4ba79e037d3e4eecdc1b

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07834043B2