Methyl 4-aminobenzoate → Methyl 4-{[cyclohexyl(3-methylthieno[2,3-b]pyridin-2-yl)methyl]amino}benzoate

To a mixture of cyclohexyl(3-methylthieno[2,3-b]pyridin-2-yl)methanone (1.00 g) synthesized above, methyl 4-aminobenzoate (642 mg), triethylamine (4.31 mL) and methylene chloride (20 mL) was added titanium (IV) chloride (508 μL) at 0° C., and the mixture was stirred at room temperature for 1.5 days under argon atmosphere. 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 solid. To a solution (20 mL) of the obtained solid in tetrahydrofuran were added acetic acid (442 μL) and sodium cyanoborohydride (485 mg), and the mixture was stirred at room temperature 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 the title object compound (975 mg, 64%) as a pale-brown 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 solid
8. stirringthe mixture was stirred at room temperature for 1.5 hr
9. customto quench
10. customthe reaction
11. extractionthe reaction 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 (30-70% ethyl acetate/hexane)

ORD record

ord-83eae030063f42719b4b0ff9d52c24f7

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08436043B2