p-Toluenesulfonic acid → HCID 66743838, compound

A mixture of 3-amino-5-bromothiophene-2-carboxamide (221 mg, 1.0 mmol), 4,4,4-trifluorobutan-2-one (1.26 g, 10 mmol), PTSA (19.0 mg, 0.1 mmol) and acetic acid (2 mL) was microwave-irradiated at 120° C. for 1 h. Then, the mixture was poured into saturated aqueous NaHCO3 (100 mL). Extraction with EtOAc (100 mL), washing with brine, drying over MgSO4, filtration and concentration under reduced pressure gave a yellow solid. This residue was mixed with 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (582 mg, 3.0 mmol), sodium carbonate (530 mg, 5.0 mmol), 1,2-dimethoxyethane (5 mL) and water (2.5 mL). The mixture was purged with argon. Then, 1,1′-bis(diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (82 mg, 0.10 mmol) was added, and the mixture was purged with argon again. This mixture was refluxed for 6 h. Then, the mixture was poured into saturated aqueous NaHCO3 (200 mL) and EtOAc (200 mL), and the mixture was shaken well. The insoluble materials were filtered off. From the filtrate, the organic layer was collected, washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. This residue was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc) to afford a yellow solid (105 mg). This solid was triturated with EtOAc/hexane and collected by filtration to afford the title compound (89.3 mg, 28%) as a yellow solid:

1. customwas microwave-irradiated at 120° C. for 1 h
2. extractionExtraction with EtOAc (100 mL)
3. washwashing with brine
4. dry with materialdrying over MgSO4, filtration and concentration under reduced pressure
5. customgave a yellow solid
6. customThe mixture was purged with argon
7. customthe mixture was purged with argon again
8. temperatureThis mixture was refluxed for 6 h
9. additionThen, the mixture was poured into saturated aqueous NaHCO3 (200 mL) and EtOAc (200 mL)
10. filtrationThe insoluble materials were filtered off
11. customFrom the filtrate, the organic layer was collected
12. washwashed with brine
13. dry with materialdried over MgSO4
14. filtrationfiltered
15. concentrationconcentrated under reduced pressure
16. customThis residue was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc)

ORD record

ord-e08f2dbc17574e8ba4919a2283cab333

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691828B2