反应详情

温度

90 °C

To a solution of methyl 3-amino-5-tert-butylpyrrole-2-carboxylate (12 mg, 0.062 mmol) and anh. pyridine (0.25 mL, 3.06 mmol, 49.4 equiv) in anh. toluene (1 mL) was rapidly added phosgene (1.93M in toluene, 0.32 mL, 0.62 mmol, 10 equiv). After 30 min, the orange suspension was concentrated under reduced pressure, then successively charged with anh. toluene (1 mL) and concentrated (2×). Finally, toluene (2 mL) was added followed by p-toluidine (10 mg, 0.094 mmol). The mixture was heated at 90° C. for 3 h, then was concentrated under reduced pressure. The residue was purified by preparative TLC (2 plates, 20×20 cm×0.25 mm, 2% MeOH/CH2Cl2). The major UV-active band was isolated and the product was extracted from the silica using 5% MeOH/CH2Cl2 to give N-(2-carbomethoxy-5-tert-butyl-3-pyrrolyl)-N′-(4-methylphenyl)urea as a pale yellow amorphous solid (0.016 g, 80%): 1H NMR (d6-DMSO ) δ1.23 (s, 9H), 2.20 (s, 3H), 3.78 (s, 3H), 6.54 (d, J=3.0 Hz, 1H), 7.04 (d, J=8.5 Hz, 2H), 7.32 (d, J=8.5 Hz, 2H), 8.61 (s, 1H), 9.51 (s, 1H), 10.85 (br d, J=2.2 Hz, 1H); 13C NMR (MeOD, CDCl3, partial spectrum) δ19.7, 29.0 (3C), 31.5, 50.0, 97.4, 105.9, 119.6 (2C), 128.9 (2C), 132.2, 136.2, 147.6, 153.5, 161.9; FTIR (KBr) 3341 (s), 2947 (m), 1676 (s), 1583 (s), 1548 (s), 1456 (s), 1279 (s), 1208 (s), 1094 (s); cm−1; FAB-LRMS m/z (rel abundance) 330 (M+H, 47%).

1. concentrationthe orange suspension was concentrated under reduced pressure
2. additionsuccessively charged with anh. toluene (1 mL)
3. concentrationconcentrated (2×)
4. additionFinally, toluene (2 mL) was added
5. concentrationwas concentrated under reduced pressure
6. customThe residue was purified by preparative TLC (2 plates, 20×20 cm×0.25 mm, 2% MeOH/CH2Cl2)
7. customThe major UV-active band was isolated
8. extractionthe product was extracted from the silica using 5% MeOH/CH2Cl2