反应详情

温度

-20 °C

To a cold (−78° C.), stirred solution of N-[3-benzenesulfinylmethyl-5-(2-fluorophenyl)-3H-1,2,3-triazol-4-yl]-2-chloro-2-cyclobutylacetamide (166 mg. 0.37 mmol) in dry tetrahydrofuran (20 ml) under nitrogen was added a solution of potassium bis(trimethylsilyl)amide (1.8 ml, 0.752 M in toluene, 1.3 mmol) and the reaction stirred for 2 hours. The reaction was allowed to warm to −20° C. and maintained at this temperature for 45 minutes before quenching by careful addition to water (100 ml). The aqueous mixture was stirred for 5 minutes and then acidified with citric acid solution (25 ml, 10% aqueous). The aqueous was extracted with ethyl acetate (2×70 ml) and the combined organic extracts were washed with water (50 l), brine (50 l), dried (Na2SO4) and evaporated in vacuo to approximately 2 ml total volume. The concentrated solution was allowed to stand at room temperature for 16 hours. The solid precipitate thus formed was collected by filtration and washed with diethyl ether to afford 6-cyclobutyl-3-(2-fluorophenyl)-4H-1,2,3-triazolo[1,5-α]pyrimidin-5-one (45 mg, 43%) as a pale solid which was used in subsequent reactions without further purification. δH (400 MHz, d6-DMSO) 1.78-1.89 (1H, m, CH(CH2)3), 1.93-2.0 4(1H, m, CH(CH2)3), 2.11-2.31 (4H, m, CH(CH2)3), 3.47 (1H, quintet, J=8.6 Hz, CH(CH2)3), 7.30-7.35 (2H, m, ArH, 7.44-7.50 (1H, m, ArH), 7.69 (1H, t, J=7.2 Hz, ArH), 8.82 (1H, s, CH═C.), 12.33 (1H, br s, NH); m/z (ES+) 285 (M+H+).

1. temperaturemaintained at this temperature for 45 minutes
2. custombefore quenching by careful addition to water (100 ml)
3. stirringThe aqueous mixture was stirred for 5 minutes
4. extractionThe aqueous was extracted with ethyl acetate (2×70 ml)
5. washthe combined organic extracts were washed with water (50 l), brine (50 l)
6. dry with materialdried (Na2SO4)
7. customevaporated in vacuo to approximately 2 ml total volume
8. waitto stand at room temperature for 16 hours
9. customThe solid precipitate thus formed
10. filtrationwas collected by filtration
11. washwashed with diethyl ether