Triethylamine → HCID 59255351, compound

To a methanol (5.00 mL) solution of 2-(4-fluoro-phenoxymethyl)-5-(2-nitro-vinyl)-pyridine (50.0 mg, 0.181 mmol) described in Manufacturing Example 72-1-3 was added lithium methoxide (13.7 mg, 0.362 mmol) under nitrogen atmosphere, which was stirred for 30 minutes at room temperature. The reaction mixture was concentrated under a reduced pressure, and anhydrous dichloromethane (4.00 mL) and anhydrous tetrahydrofuran (2.00 mL) were added to the residue. Titanium (IV) tetrachloride (63.7 μL, 0.579 mmol) was added dropwise to the reaction mixture on a dry ice-ethanol bath (−78° C.), after which the system was stirred for 40 minutes at 0° C. Water and ethyl acetate were added to the reaction mixture on an ice bath (0° C.), and the organic layer was extracted with ethyl acetate. This organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and then filtered. The filtrate was concentrated under a reduced pressure to obtain a crude product (43.0 mg). To a tetrahydrofuran (5.00 mL) solution of 3-ethynyl-pyridin-2,6-diamine (4.00 mg, 0.030 mmol) described in Manufacturing Example 13-1-3 and this crude product (20.0 mg) was added triethylamine (12.5 μL, 0.090 mmol), which was stirred for 2 hours at room temperature. Water was added to the reaction solution at room temperature, which was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. The residue was purified by reverse-phase high performance liquid chromatography (using an acetonitrile-water mobile phase containing 0.1% trifluoroacetic acid) to obtain the title compound (1.53 mg, 25.4%) as a ditrifluoroacetic acid salt.

1. concentrationThe reaction mixture was concentrated under a reduced pressure, and anhydrous dichloromethane (4.00 mL) and anhydrous tetrahydrofuran (2.00 mL)
2. additionwere added to the residue
3. stirringafter which the system was stirred for 40 minutes at 0° C
4. extractionthe organic layer was extracted with ethyl acetate
5. washThis organic layer was washed with water and saturated aqueous sodium chloride
6. dry with materialdried over anhydrous magnesium sulfate
7. filtrationfiltered
8. concentrationThe filtrate was concentrated under a reduced pressure
9. customto obtain a crude product (43.0 mg)
10. stirringwas stirred for 2 hours at room temperature
11. extractionwhich was extracted with ethyl acetate
12. washThe organic layer was washed with a saturated aqueous sodium chloride
13. dry with materialdried over anhydrous magnesium sulfate
14. customthe solvent was evaporated under a reduced pressure
15. customThe residue was purified by reverse-phase high performance liquid chromatography (
16. additioncontaining 0.1% trifluoroacetic acid)

ORD record

ord-df4babcb34254569842ba28344b0c70f

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08841327B2