p-Toluenesulfonic acid → HCID 66743248, compound

Temperature

70 °C

A mixture of 5-bromo-3-[(2-hydroxyethyl)amino]thiophene-2-carboxamide (100 mg, 0.377 mmol), acetone (1.0 mL), PTSA (6.5 mg, 0.038 mmol) and acetic acid (1.0 mL) was stirred at 70° C. for 1 h. The mixture was poured into saturated aqueous NaHCO3. The organic materials were extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, a pale brown amorphous solid was obtained. A flask was charged with the amorphous, 1,2-dimethoxyethane (3.0 mL), tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (349 mg, 1.13 mmol), sodium carbonate (113 mg, 1.89 mmol) and water (1.5 mL). The flask was purged with argon. Then, 1,1′-bis(diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (31 mg, 0.038 mmol) was added to the mixture. The flask was purged with argon. After stirring at 100° C. for 1 h, 8 M aqueous NaOH (1.0 mL) was added. After stirring at 100° C. for 1.5 h, the organic materials were extracted with EtOAc/THF. The combined extracts were washed with 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 then to 90:10 EtOAc/MeOH), then crystallized from MeOH/EtOAc/hexane) to give the title compound (40 mg, 35%) as a pale brown solid:

1. extractionThe organic materials were extracted with EtOAc
2. washThe combined extracts were washed with brine
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. customAfter removal of the solvent at reduced pressure
6. customa pale brown amorphous solid was obtained
7. customThe flask was purged with argon
8. customThe flask was purged with argon
9. stirringAfter stirring at 100° C. for 1 h
10. addition8 M aqueous NaOH (1.0 mL) was added
11. stirringAfter stirring at 100° C. for 1.5 h
12. extractionthe organic materials were extracted with EtOAc/THF
13. washThe combined extracts were washed with brine
14. dry with materialdried over Na2SO4
15. filtrationfiltered
16. customAfter removal of the solvent at reduced pressure
17. customthe residue was purified by column chromatography (Purif, silica gel, 90:10 hexane/EtOAc to EtOAc
18. customto 90:10 EtOAc/MeOH), then crystallized from MeOH/EtOAc/hexane)

ORD record

ord-7311991fc1014fee9d60c23640d8dcd5

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691828B2