1,2-Dimethoxyethane → 1,2,2-trimethyl-6-(1H-pyrazol-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one

A mixture of 6-bromo-1,2,2-trimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one (138 mg, 0.50 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (291 mg, 1.50 mmol), sodium carbonate (265 mg, 2.50 mmol), 1,2-dimethoxyethane (5 mL) and water (2.5 mL) was purged with argon. Then, 1,1′-bis(diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (40.8 mg, 0.050 mmol) was added, and the mixture was purged with argon again. This mixture was refluxed for 18 h. Then, the mixture was poured into saturated aqueous NaHCO3 (100 mL) and EtOAc (100 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, then EtOAc to 90:10 EtOAc/MeOH) to afford a white solid (60 mg). This solid was triturated with EtOAc/hexane and collected by filtration to afford the title compound (50.3 mg, 38%) as a white solid:

1. customwas purged with argon
2. customthe mixture was purged with argon again
3. temperatureThis mixture was refluxed for 18 h
4. additionThen, the mixture was poured into saturated aqueous NaHCO3 (100 mL) and EtOAc (100 mL)
5. filtrationThe insoluble materials were filtered off
6. customFrom the filtrate, the organic layer was collected
7. washwashed with brine
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThis residue was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc

ORD record

ord-dda5d04451dd48709ab7312fe444bb5f

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691828B2