p-Toluenesulfonic acid → HCID 66743287, compound

Temperature

90 °C

A mixture of 3-amino-5-bromothiophene-2-carboxamide (221 mg, 1 mmol), PTSA (9.5 mg, 0.050 mmol), cyclohexanone (2.94 g, 30.0 mmol) and acetic acid (2 mL) was stirred at 90° C. for 2 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, 3.00 mmol), sodium carbonate (530 mg, 5.00 mmol), 1,2-dimethoxyethane (2 mL) and water (2 mL). The mixture was purged with argon. Then, 1,1′-bis(diphenylphosphino) ferrocenepalladium (II) dichloride dichloromethane adduct (82 mg, 0.100 mmol) was added, and the mixture was purged with argon again. This mixture was refluxed overnight. Then, the mixture was poured into saturated aqueous NaHCO3 (200 mL) and EtOAc (200 mL). After shaking, the insoluble materials were filtered off. From the filtrate, the organic layer was collected, washed with brine, dried over MgSO4, filtered and concentrated in vacuo. This residue was purified by column chromatography (Purif, silica gel, EtOAc to 90:10 EtOAc/MeOH) to afford a yellow solid (86 mg). This solid was triturated with EtOAc/hexane and collected by filtration to afford the title compound (78.7 mg, 27%) as a yellow solid:

1. extractionExtraction with EtOAc (100 mL)
2. washwashing with brine
3. dry with materialdrying over MgSO4, filtration and concentration under reduced pressure
4. customgave a yellow solid
5. customThe mixture was purged with argon
6. customthe mixture was purged with argon again
7. temperatureThis mixture was refluxed overnight
8. additionThen, the mixture was poured into saturated aqueous NaHCO3 (200 mL) and EtOAc (200 mL)
9. stirringAfter shaking
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 in vacuo
16. customThis residue was purified by column chromatography (Purif, silica gel, EtOAc to 90:10 EtOAc/MeOH)

ORD record

ord-38ca9323a3f84dd0ad1a2b26e43c8378

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691828B2