Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 1-ethyl-6'-(5-methyl-1H-pyrazol-4-yl)-1'H-spiro [piperidine-4,2'-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 (100 mg, 0.45 mmol), 1-ethylpiperidin-4-one (0.067 mL, 0.50 mmol), CSA (125 mg, 0.54 mmol), MgSO4 (108 mg, 0.90 mmol) and DMA (2.0 mL) was stirred at 100° C. for 4 h. Then, the mixture was poured into saturated aqueous NaHCO3. The organic materials were extracted with EtOAc. To the aqueous layer, NaCl was added. The organic materials were extracted again with EtOAc/THF. The combined organic layers were concentrated under reduced pressure. The residue was purified by column chromatography (Purif, NH, 80:20 hexane/EtOAc to EtOAc then to 90:10 EtOAc/MeOH), then crystallized from MeOH/EtOAc/hexane to give the title compound (89 mg, 64%) as yellow solid:

Provenance & Evidence