Trifluoroacetic acid → HCID 66777568, compound

To a mixture of 3-methyl-1-(3-methyl-1-benzothiophen-2-yl)butan-1-one (1.00 g) synthesized in Example A32(1), methyl 6-aminopyridine-3-carboxylate (654 mg), triethylamine (4.79 mL) and dichloromethane (20 mL) was added titanium (IV) chloride (566 μL) at 0° C., and the mixture was stirred overnight at room temperature. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to give a dark brown solid. To a mixture of the obtained solid, acetic acid (2 mL) and tetrahydrofuran (20 mL) was added sodium cyanoborohydride (540 mg), and the mixture was stirred at room temperature for 2 hr. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4, volume ratio) to give a pale-brown solid. To a mixture of the obtained solid, trifluoroacetic acid (1.00 mL) and ethanol (10 mL) was added sodium cyanoborohydride (251 mg), and the mixture was stirred at room temperature for 1 hr. In addition, sodium cyanoborohydride (251 mg) was added, and the mixture was stirred at room temperature for 30 min then at 50° C. for 1 hr. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to give the title object compound (743 mg, 47%) as a pale-yellow solid.

1. customto quench
2. customthe reaction
3. extractionthe mixture was extracted with ethyl acetate
4. washThe extract was washed with saturated brine
5. dry with materialdried over magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. customto give a dark brown solid
8. stirringthe mixture was stirred at room temperature for 2 hr
9. customto quench
10. customthe reaction
11. extractionthe mixture was extracted with ethyl acetate
12. washThe extract was washed with saturated brine
13. dry with materialdried over magnesium sulfate
14. concentrationconcentrated under reduced pressure
15. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4, volume ratio)
16. customto give a pale-brown solid
17. stirringthe mixture was stirred at room temperature for 1 hr
18. stirringthe mixture was stirred at room temperature for 30 min
19. waitat 50° C. for 1 hr
20. customto quench
21. customthe reaction
22. extractionthe mixture was extracted with ethyl acetate
23. washThe extract was washed with saturated brine
24. dry with materialdried over magnesium sulfate
25. concentrationconcentrated under reduced pressure

ORD record

ord-1996094c7bd642e983d72da5ec81b9a8

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08436043B2