Hydrochloric Acid → HCID 66743236, compound

Temperature

100 °C

To a solution of methyl 5-bromo-3-[(pyridin-4-ylmethyl)amino]thiophene-2-carboxylate (238 mg, 0.727 mmol) in MeOH (2 mL) and ethanol (10 mL) was added a solution of sodium hydroxide (87 mg, 2.18 mmol) in water (1 mL). After stirring at 100° C. for 5 h, 6 M aqueous HCl (0.23 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 (4 mL). Then, triethylamine (2.0 mL, 15 mmol) and ammonium chloride (777 mg, 15 mmol) were added. After stirring at room temperature for 5 min, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (836 mg, 4.4 mmol) and 1-hydroxybenzotriazole (589 mg, 4.4 mmol) were added to the mixture, and stirring was continued for 18 h. Then, water and EtOAc were 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, 90:10 hexane/EtOAc to EtOAc) to give the title compound (167 mg, 74%) as a brown solid:

1. customAfter removal of the solvent at reduced pressure
2. additionthe residue was diluted with DMF (4 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, 90:10 hexane/EtOAc to EtOAc)

ORD record

ord-f577ab99774e4073b0f598ab3f5f2dbc

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691828B2