Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 2-fluoro-1'-methyl-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 3-(methylamino)-5-(5-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide (70 mg, 0.30 mmol), 2-fluorocyclohexanone (105 mg, 0.90 mmol), CSA (7.0 mg, 0.030 mmol), MgSO4 (72 mg, 0.60 mmol) and DMA (1 mL) was stirred at 70° C. for 5.5 h. Then, saturated aqueous NaHCO3 and EtOAc were added to quench the reaction. The organic materials were extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, 80:20 hexane/EtOAc to EtOAc), then crystallized from MeOH/EtOAc/hexane to give the title compound (58 mg, 58%) as a yellow solid:

Provenance & Evidence