Hydrochloric Acid → HCID 66744051, compound

A mixture of methyl 5-bromo-3-[(trifluoroacetyl)amino]thiophene-2-carboxylate (500 mg, 1.55 mmol), (2-bromoethoxy) (tert-butyl)dimethylsilane (0.99 mL, 4.66 mmol), cesium carbonate (1.52 g, 4.66 mmol), sodium iodide (24 mg, 0.16 mmol) and DMF (3 mL) was microwave-irradiated at 130° C. for 1.5 h. Then, water was added to quench the reaction. The organic materials were extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was dissolved in MeOH (20 mL). To the solution were added potassium carbonate (1.86 g) and water (5 mL). The mixture was stirred at room temperature for 2 h. After removal of the solvent at reduced pressure, the organic materials were extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, hexane to 80:20 hexane/EtOAc) to give a yellow oil. The oil was mixed with MeOH (4 mL), water (2 mL) and sodium hydroxide (147 mg, 3.68 mmol). The mixture was stirred at 70° C. for 6 h. Then, 6 M aqueous HCl (0.39 mL) was added to the mixture to adjust the pH to 10. After removal of the solvent at reduced pressure, the residue was mixed with ammonium chloride (1.32 g, 24.6 mmol), triethylamine (3.4 mL, 24.6 mmol) and DMF (6.0 mL). After stirring at room temperature for 5 min, 1-hydroxybenzotriazole (997 mg, 7.38 mmol) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (1.41 g, 7.38 mmol) were added. After stirring at room temperature for 18 h, water and EtOAc were added to quench the reaction. The organic materials were extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 sulfate and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, hexane to EtOAc) to give the title compound (108 mg, 26%) as a pale brown solid:

1. customwas microwave-irradiated at 130° C. for 1.5 h
2. customto quench
3. customthe reaction
4. extractionThe organic materials were extracted with EtOAc
5. washThe combined extracts were washed with water and brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. customAfter removal of the solvent at reduced pressure
9. dissolutionthe residue was dissolved in MeOH (20 mL)
10. additionTo the solution were added potassium carbonate (1.86 g) and water (5 mL)
11. customAfter removal of the solvent at reduced pressure
12. extractionthe organic materials were extracted with EtOAc
13. washThe combined extracts were washed with brine
14. dry with materialdried over Na2SO4
15. filtrationfiltered
16. customAfter removal of the solvent at reduced pressure
17. customthe residue was purified by column chromatography (Purif, silica gel, hexane to 80:20 hexane/EtOAc)
18. customto give a yellow oil
19. stirringThe mixture was stirred at 70° C. for 6 h
20. customAfter removal of the solvent at reduced pressure
21. stirringAfter stirring at room temperature for 5 min
22. stirringAfter stirring at room temperature for 18 h
23. customto quench
24. customthe reaction
25. extractionThe organic materials were extracted with EtOAc
26. washThe combined extracts were washed with water and brine
27. dry with materialdried over Na2SO4 sulfate
28. filtrationfiltered
29. customAfter removal of the solvent at reduced pressure
30. customthe residue was purified by column chromatography (Purif, silica gel, hexane to EtOAc)

ORD record

ord-389e2a9c201147479b2db1ddf18eacf4

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691828B2