Tetrahydrofuran → HCID 58227475, compound

Participants

Reaction Steps

In a culture tube was added pyrrolidine (17.8 mg, 0.250 mmol) and benzotriazole (29.8 mg, 0.250 mmol) in ethanol (1.0 mL). After stirring at room temperature for 10 minutes, the solution was treated with 2-phenylethynyl-thiazole-5-carbaldehyde (Example 205, 53.3 mg, 0.250 mmol) and THF (0.5 to 1.0 mL) and stirred at room temperature for 1 hour. The volatiles were then removed under reduced pressure, the residue dissolved in ethanol (1.0 mL) and THF (1.0 mL) and the volatiles removed again under reduced pressure. The residue was dissolved once more in THF (1.0 mL), concentrated under reduced pressure and kept under high vacuum for about 1 hour. The residue was then dissolved in THF (1.0 mL) and treated with methyl magnesium bromide (170 μL of a 3.0 M solution in diethyl ether, 0.50 mmol) and the reaction was stirred at room temperature. The reaction was quenched by adding saturated aqueous sodium bicarbonate (4 mL) and diluted with EtOAc (4 mL). After stirring vigorously for a few minutes, the layers were separated and the aqueous layer was stirred again with EtOAc (4 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified on a reversed phase liquid chromatography/mass spectrometry (RP-HPLC/MS) purification system. Gradient: acetonitrile in water, 28-95% in 3.6 minutes with a cycle time of 5 min. A shallow gradient between 38-68% of acetonitrile was used between 0.75-3.3 min to separate close-eluting impurities. Flow rate: 100 mL/min. Mobile phase additive: 96 mM of ammonium formate. Column: Inertsil® C18, 30×50 mm, 5 μm particle size (GL Sciences, Tokyo, Japan)). Fractions were concentrated under reduced pressure and the solid obtained was partitioned between EtOAc (5 mL) and saturated aqueous sodium bicarbonate (5 mL). After stirring vigorously for a few seconds, the layers were separated and the aqueous layer was stirred again with EtOAc (5 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to afford the titled compound, 2-phenylethynyl-5-(1-pyrrolidin-1-yl-ethyl)-thiazole, (26 mg, 37%) as an amber oil.

Provenance & Evidence