Tributylphosphine → ethyl{2-(7-[(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetate

Temperature

50 °C

A mixture of 7-[(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indole-2-carboxamide (2.14 g), Lawesson's reagent (2.14 g) and tetrahydrofuran (50 mL) was stirred at 50° C. for 1.5 hr, and heated under reflux for 1.5 hr. The reaction mixture was concentrated, and the residue was washed with diisopropyl ether to give pale-yellow crystals. The obtained crystals were subjected to silica gel column chromatography, and eluted with hexane-ethyl acetate (4:1-1:2, volume ratio) to give yellow crystals. A mixture of the obtained crystals, ethyl but-2-ynoate (1.49 g), tributylphosphine (1.07 g), toluene (30 mL) and tetrahydrofuran (10 mL) was stirred at 70° C. for 5 hr. ethyl but-2-ynoate (900 mg) and tributylphosphine (1.07 g) were added to the mixture, and the mixture was further stirred at room temperature for 2.5 days. The reaction mixture was concentrated, and the residue was subjected to silica gel column chromatography, and eluted with hexane-ethyl acetate (4:1-1:3, volume ratio) to give the title compound (780 mg, yield 28%) as a brown oil.

1. temperatureheated
2. temperatureunder reflux for 1.5 hr
3. concentrationThe reaction mixture was concentrated
4. washthe residue was washed with diisopropyl ether
5. customto give pale-yellow crystals
6. washeluted with hexane-ethyl acetate (4:1-1:2, volume ratio)
7. customto give yellow crystals
8. stirringwas stirred at 70° C. for 5 hr
9. stirringthe mixture was further stirred at room temperature for 2.5 days
10. concentrationThe reaction mixture was concentrated
11. washeluted with hexane-ethyl acetate (4:1-1:3, volume ratio)

ORD record

ord-6120723468a54291bcfd7055039604aa

Source dataset

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07777047B2