Hydrochloric Acid → HCID 66743408, compound

Temperature

100 °C

To a solution of methyl 5-bromo-3-[(pyridin-2-ylmethyl)amino]thiophene-2-carboxylate (336 mg, 1.03 mmol) in MeOH (3 mL) and ethanol (10 mL) was added a solution of sodium hydroxide (124 mg, 3.09 mmol) in water (1.5 mL). After stirring at 100° C. for 5 h, 6 M aqueous HCl (0.33 mL) was added to the mixture to adjust the pH to 10. After removal of the solvent at reduced pressure, the residue was diluted with DMF (5 mL). Then, triethylamine (2.9 mL, 21 mmol) and ammonium chloride (1.1 g, 21 mmol) were added. After stirring at room temperature for 5 min, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (1.2 g, 6.2 mmol) and 1-hydroxybenzotriazole (835 mg, 6.2 mmol) were added to the mixture, and stirring was continued for 18 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 purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc) to give the title compound (160 mg, 50%) as a yellow solid:

1. customAfter removal of the solvent at reduced pressure
2. additionthe residue was diluted with DMF (5 mL)
3. stirringAfter stirring at room temperature for 5 min
4. stirringstirring
5. waitwas continued for 18 h
6. customto quench
7. customthe reaction
8. extractionThe organic materials were extracted with EtOAc
9. washThe combined extracts were washed with water and brine
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. customAfter removal of the solvent at reduced pressure
13. customthe residue was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc)

ORD record

ord-59b0a5b942cd4aa4996f9e605180cb4e

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691828B2