Ethylenediamine → HCID 86761829, compound

To a mixture of cyclohexyl(3-methylthieno[3,2-c]pyridin-2-yl)methanone (864 mg) synthesized above, methyl 4-aminobenzoate (553 mg), triethylamine (3.71 mL) and methylene chloride (20 mL) was added titanium (IV) chloride (439 μL) at 0° C., and the mixture was stirred under argon atmosphere overnight at room temperature. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, and the reaction 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 oil. To a solution (20 mL) of the obtained oil in tetrahydrofuran were added acetic acid (268 μL) and sodium cyanoborohydride (419 mg), and the mixture was stirred at room temperature stirred for 1.5 hr. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, and the reaction 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 (30-70% ethyl acetate/hexane) to give a pale-brown solid. To a mixture of the obtained solid, tetrahydrofuran (5 mL) and ethanol (5 mL) was added 1N aqueous sodium hydroxide solution (5.00 mL), and the mixture was stirred overnight with heating under reflux. Tetrahydrofuran (5 mL), ethanol (5 mL) and 1N aqueous sodium hydroxide solution (5.00 mL) were additionally added, and the mixture was stirred with heating under reflux for 2.5 hr, and ethylenediamine (1.00 mL) was added. The mixture was stirred with heating under reflux for 4 hr, and concentrated under reduced pressure. The residue was acidified with 1N hydrochloric acid to pH=4, 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 (50-100% ethyl acetate/hexane) to give the title object compound (432 mg, 34%) as a pale-yellow solid.

1. customto quench
2. customthe reaction
3. extractionthe reaction 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 oil
8. stirringthe mixture was stirred at room temperature
9. stirringstirred for 1.5 hr
10. customto quench
11. customthe reaction
12. extractionthe reaction mixture was extracted with ethyl acetate
13. washThe extract was washed with saturated brine
14. dry with materialdried over magnesium sulfate
15. concentrationconcentrated under reduced pressure
16. customThe residue was purified by silica gel column chromatography (30-70% ethyl acetate/hexane)
17. customto give a pale-brown solid
18. stirringthe mixture was stirred overnight
19. temperaturewith heating
20. temperatureunder reflux
21. stirringthe mixture was stirred
22. temperaturewith heating
23. temperatureunder reflux for 2.5 hr
24. stirringThe mixture was stirred
25. temperaturewith heating
26. temperatureunder reflux for 4 hr
27. concentrationconcentrated under reduced pressure
28. extractionthe mixture was extracted with ethyl acetate
29. washThe extract was washed with saturated brine
30. dry with materialdried over magnesium sulfate
31. concentrationconcentrated under reduced pressure
32. customThe residue was purified by silica gel column chromatography (50-100% ethyl acetate/hexane)

ORD record

ord-8d6d8233e87e4628b6030715926ddc8b

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08436043B2