反应详情

温度

140 °C

Ammonium acetate (9.4 g, 157 mmol) was added to a solution of Example J7, (2S)-tert-butyl 2-(4-(methoxy)-1-(4-bromophenyl)-1,4-dioxobutan-2-ylcarbamoyl)pyrrolidine-1-carboxylate (7.6 g, 15.7 mmol) in xylene (80 mL) and stirred for 4 hours at 140° C. in a screw capped 150 mL pressure vessel. After being cooled, the reaction mixture was diluted with ethyl acetate and washed with sat NaHCO3 and brine before being concentrated by rotory evaporation under high vacuum. The crude product was taken up in CH2Cl2 and charged to a 40 (M) Biotage silica gel cartridge. Gradient elution 15-100% B over 2 L (A=CH2Cl2; B=ethyl acetate) gave Example J8, (S)-tert-butyl 2-(4-(4-bromophenyl)-5-(2-methoxy-2-oxoethyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate 3.38 g (46%). 1H NMR (500 MHz, DMSO-d6) δ 7.54 (s, 4H), 4.83-4.73 (m, 1H), 3.81 (br. s, 1H), 3.62 (s, 3H), 3.53-3.51 (m, 1H), 3.38-3.31 (m, 2H), 2.25-2.15 (m, 1H), 1.99-1.83 (m, 3H), 1.41/1.16 (s, 9H). RT=1.6 minutes (Condition 1). LCMS: Anal. Calcd. for C21H26BrN3O4 464.11; found: 464.40 (M+H)+.

1. customcapped 150 mL pressure vessel
2. temperatureAfter being cooled
3. washwashed
4. concentrationbefore being concentrated by rotory evaporation under high vacuum
5. additioncharged to a 40 (M) Biotage silica gel cartridge
6. washGradient elution 15-100% B over 2 L (A=CH2Cl2