Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 2-fluoro-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-amino-5-(5-methyl-1H-pyrazol-4-yl)thiophene -2-carboxamide (66 mg, 0.30 mmol), 2-fluorocyclohexanone (0.10 mL, 0.90 mmol), CSA (7.0 mg, 0.030 mmol), MgSO4 (72 mg, 0.60 mmol) and DMA (1 mL) was stirred at 80° C. for 2 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. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel 85:15 hexane/EtOAc to EtOAc), then crystallized from MeOH/EtOAc/hexane) to give the title compound (53 mg, 55%) as a pale yellow solid:

Provenance & Evidence