反应详情

温度

0 °C

To a solution of 2-(1H-benzo[d][1,2,3]triazol-1-yl)-2-(((benzyloxy)carbonyl)amino)acetic acid (608 mg, 1.864 mmol) in THF (7 mL) cooled at 0° C. was added oxalyl chloride (0.157 mL, 1.789 mmol), followed by DMF (0.02 mL). The resulting mixture was stirred at 0° C. for 1.5 h. Then a solution of Intermediate 37F (268 mg, 0.745 mmol) and 4-methylmorpholine (0.246 mL, 2.236 mmol) in THF (3 mL) were slowly added. After the addition, the reaction mixture was warmed to room temperature and stirred for 1 h. Next, 7N ammonia in MeOH (4 mL, 28.0 mmol) was added and the mixture was stirred at room temperature overnight. The resulting mixture was concentrated and the residue was treated with EtOAc and water. The organic layer was separated, and the aqueous layer was extracted with EtOAc. The combined organic extracts were washed with 1N NaOH, sat NaHCO3 and brine and then dried over MgSO4, filtered and concentrated. The residue was then dissolved in acetic acid (1.5 mL, 26.2 mmol), and treated with ammonium acetate (287 mg, 3.73 mmol). The mixture was stirred at 40° C. for 2 h. The reaction mixture was then treated with water and extracted with EtOAc. The combined extracts were washed with water, saturated NaHCO3, and brine and then dried and concentrated. The crude material was purified by flash chromatography (SiO2, 12 g column, EtOAc/hexane=0-40%) to afford Intermediate 37G (256 mg, 63%). HPLC: RT=3.61 min (CHROMOLITH® SpeedROD column 4 6×50 mm, 10-90% aqueous methanol over 4 minutes containing 0.1% TFA, 4 mL/min, monitoring at 220 nm), MS(ES): m/z=548.5 [M+H+].

1. additionAfter the addition
2. temperaturethe reaction mixture was warmed to room temperature
3. stirringstirred for 1 h
4. stirringthe mixture was stirred at room temperature overnight
5. concentrationThe resulting mixture was concentrated
6. additionthe residue was treated with EtOAc and water
7. customThe organic layer was separated
8. extractionthe aqueous layer was extracted with EtOAc
9. washThe combined organic extracts were washed with 1N NaOH
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated
13. stirringThe mixture was stirred at 40° C. for 2 h
14. extractionextracted with EtOAc
15. washThe combined extracts were washed with water, saturated NaHCO3, and brine
16. customdried
17. concentrationconcentrated
18. customThe crude material was purified by flash chromatography (SiO2, 12 g column, EtOAc/hexane=0-40%)