Hydrochloric Acid → HCID 66743324, compound

Participants

Reaction Steps

A mixture of 1-ethyl-2-methyl-6-(5-methyl-1H-pyrazol-4-yl)-2-(2,2,2-trifluoroethyl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one (120 mg, 0.335 mmol) and TFA (1.0 mL) was stirred at room temperature for 1 day. After removal of the solvent at reduced pressure, the residue was treated with saturated aqueous NaHCO3. The organic materials were extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, EtOAc) to give a yellow crystalline solid. The solid was dissolved in DMA (1.5 mL). To the mixture, 2,2-dimethoxypropane (1.5 mL), CSA (15 mg) and MgSO4 (100 mg) were added. The mixture was stirred at 80° C. for 2 h. The mixture was poured into saturated aqueous NaHCO3. 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, EtOAc) to give a yellow crystalline solid. The solid was mixed with MeOH (1.0 mL) and 1 M aqueous HCl (1.0 mL). After stirring at 50° C. for 1 h, saturated aqueous NaHCO3 was added to the mixture. The organic materials were extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was dissolved in acetic acid (0.50 mL). To the solution were added acetone (1.0 mL) and PTSA (10 mg). After stirring at 60° C. for 1 h, saturated aqueous NaHCO3 and EtOAc were added to the mixture. The organic materials were extracted with EtOAc. The combined extracts were washed with brine, and then dried over Na2SO4. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, 90:10 hexane/EtOAc to EtOAc), then crystallized from EtOAc/heptane to give the title compound (24 mg, 24%) as a colorless solid:

Provenance & Evidence