反应详情

Methyl 4-(tert-butoxycarbonylamino)-1-methyl-1H-imidazole-2-carboxylate (2.50 g, 9.80 mmol) in 30 ml of EtAc was added 6 ml of HCl (conc.). After stirring for 45 min, the mixture was diluted with ethanol and toluene, concentrated and co-evaporated with ethanol/toluene (1:1, 3×50 ml) to dryness without further purification. To the dry compound was added 4-(tert-butoxycarbonylamino)-1-methyl-1H-pyrrole-2-carboxylic acid (2.35 g, 9.8 mmol), EDC (5.60 g, 29.1 mmol), DIPEA (1.70 ml, 9.8 mmol) and 80 ml of DMA. The mixture was stirred under Ar overnight, concentrated, diluted with THF/EtAc (1:2, 150 ml), and washed 1M NaH2PO4/NaCl (conc) and NaHCO3 (conc) separately. The organic solvent layer was separated and dried over MgSO4, filtered, concentrated and purified on SiO2 chromatography eluted with EtAc/DCM (1:25 to 1:15) to afford 2.72 g (73%) of the title product. 1H NMR (DMF-d7) 10.27 (s, 1H), 9.08 (s, 1H), 7.41 (s, 1H), 7.32 (s, 1H), 7.07 (s, 1H), 4.10 (s, 3H), 3.93 (s, 3H), 3.84 (s, 3H), 1.47 (s, 9H); 13C NMR 162.62, 161.20, 153.82, 145.32, 144.12, 132.56, 128.46, 124.39, 119.83, 79.51, 52.75, 36.06, 35.83, 28.88; MS m/z+400.2 (M+Na).

1. concentrationconcentrated and co-evaporated with ethanol/toluene (1:1, 3×50 ml) to dryness without further purification
2. stirringThe mixture was stirred under Ar overnight
3. concentrationconcentrated
4. additiondiluted with THF/EtAc (1:2, 150 ml)
5. washwashed 1M NaH2PO4/NaCl (conc) and NaHCO3 (conc) separately
6. customThe organic solvent layer was separated
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. custompurified on SiO2 chromatography
11. washeluted with EtAc/DCM (1:25 to 1:15)