Ethyl bromopyruvate → 4,5,6,7-Tetrahydro-1,3a,3b,8-tetraaza-cyclopenta[a]indene-2-carboxylic acid ethyl ester

Ethyl bromopyruvate (10.23 g) was added to the mixture of 5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (5.8 g) in 1,2-dimethoxyethane (320 mL). The reaction mixture was stirred for 5 hours at room temperature and concentrated to 100 mL under reduced pressure. The precipitate was obtained by an addition of diethyl ether (200 mL), followed by filtration. The precipitate was dissolved in ethanol (175 mL) and stirred for 20 hours at 110° C. in shield tube. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was treated with saturated potassium carbonate solution and extracted with chloroform. The organic layer was dried (Na2SO4) and concentrated under reduced pressure. The residue was applied to silica gel column chromatography, then eluted with ethyl acetate—methanol (1/1). The title compound was obtained as a pale yellow solid (7.56 g, 77%). 1H-NMR (400 MHz, CDCl3) δ 1.42 (t, 3H, J=7.1 Hz), 2.14–2.25 (m, 4H), 3.11 (t, 2H, J=6.1 Hz), 4.37 (t, 2H, J=5.7 Hz), 4.41 (q, 2H, J=7.1 Hz), 7.57 (s, 1H).

1. concentrationconcentrated to 100 mL under reduced pressure
2. customThe precipitate was obtained by an addition of diethyl ether (200 mL)
3. filtrationfollowed by filtration
4. dissolutionThe precipitate was dissolved in ethanol (175 mL)
5. stirringstirred for 20 hours at 110° C. in shield tube
6. temperatureThe reaction mixture was cooled to room temperature
7. concentrationconcentrated under reduced pressure
8. additionThe residue was treated with saturated potassium carbonate solution
9. extractionextracted with chloroform
10. dry with materialThe organic layer was dried (Na2SO4)
11. concentrationconcentrated under reduced pressure
12. washeluted with ethyl acetate—methanol (1/1)

ORD record

ord-249fa28954c5490395e8316559a1ac8f

Source dataset

uspto-grants-2006_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07018997B2