Hydrochloric Acid → 6'-(5-methyl-1H-pyrazol-4-yl)-1'H-spiro [cyclohexane-1,2'-thieno[3,2-d]pyrimidin]-4'(3'H)-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 2,2-dimethyl-6-(5-methyl-1H-pyrazol-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one (0.090 g, 0.343 mmol), 1 M HCl (1.2 mL, 1.2 mmol) and MeOH (4 mL) was stirred at 50° C. for 2 h. Then, the reaction mixture was poured into excess saturated aqueous NaHCO3 and extracted with EtOAc, and the extract was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was mixed with cyclohexanone (2 mL, 19.3 mmol), MgSO4 (0.041 g, 0.343 mmol), PTSA (3.3 mg, 0.017 mmol) and DMF (2 mL). The mixture was stirred at 80° C. for 3 h. The mixture was poured into saturated aqueous NaHCO3 and extracted with EtOAc, and the extract was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc then to 90:10 EtOAc/MeOH). The obtained oil was purified again by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc) to give a yellow solid. This solid was triturated with EtOAc/hexane and collected by filtration to afford the title compound (42.8 mg, 41%) as a yellow solid:

Provenance & Evidence