Tetrahydrofuran → Ethyl{2-[5-{[5-(methylsulfonyl)pyridin-2-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetate

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-{[5-(methylsulfonyl)pyridin-2-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indole-2-carboxamide (1.41 g), a Lawesson's reagent (1.45 g), and tetrahydrofuran (20 mL) was stirred at 70° C. for 2 hr. To the reaction solution was added a Lawesson's reagent (0.7 g), and the mixture was stirred at 70° C. for 3 hr. Furthermore, a Lawesson's reagent (0.7 g) was added, and the mixture was stirred at 50° C. for 3 days. Furthermore, a Lawesson's reagent (0.7 g) was added, and the mixture was stirred at 70° C. for 2 hr. The reaction solution was concentrated, and the residue was suspended in tetrahydrofuran (10 mL)-toluene (15 mL), tri-n-butylphosphine (1.6 mL) and ethyl 2-butynoate (1.14 mL) were added and the mixture was stirred at 70° C. for 40 min. The reaction solution was diluted with tetrahydrofuran (250 mL), tri-n-butylphosphine (1.6 mL) and ethyl 2-butynoate (1.14 mL) were added, and the mixture was stirred at 70° C. for 2.5 hr. Furthermore, tri-n-butylphosphine (0.8 mL) and ethyl 2-butynoate (1.0 mL) were added, and the mixture was stirred at 70° C. for 2 hr. The reaction solution was concentrated under reduced pressure, and the obtained crude product was subjected to basic silica gel column chromatography (ethyl acetate:hexane=10:90 to 70:30, volume ratio) to give the title compound as a brown amorphous solid (500 mg, yield 27%).

Provenance & Evidence