反应详情

温度

80 °C

To a solution of (1aR,5aR)-2-(4-iodo-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ethyl ester (1.0 g, 2.53 mmol) in acetonitrile (30 mL) was added concentrated HCl solution (2 mL). The reaction was stirred at 80° C. for 20 h. After removal of acetonitrile, the aqueous residue was diluted with water and a NaHCO3 solution was added to adjust the pH to 2-3. The resulting mixture was extracted with EtOAc (100 mL). The organic layer was washed with brine, dried over MgSO4, and concentrated. The residue was dissolved in a mixture of THF/MeOH/H2O (20/20/10) and added LiOH (61 mg). The reaction was stirred overnight and concentrated. The aqueous residue was diluted with water and an HCl solution was added to adjust the pH to 2-3. The resulting solid was filtered, washed with water and dried to give the title compound (610 mg). LCMS m/z=276.1 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 0.40 (dd, J=7.7, 4.5 Hz, 1H), 1.25 (td, J=7.9, 4.6 Hz, 1H), 2.25-2.30 (m, 1H), 2.71-2.75 (m, 1H), 2.76 (d, J=16.8 Hz, 1H), 2.87 (dd, J=16.4, 6.4 Hz, 1H), 7.55 (dd, J=5.4, 1.9 Hz, 1H), 7.90 (d, J=1.8 Hz, 1H), 8.52 (d, J=5.4 Hz, 1H), 12.98 (s, 1H).

1. customAfter removal of acetonitrile
2. additionthe aqueous residue was diluted with water
3. additiona NaHCO3 solution was added
4. extractionThe resulting mixture was extracted with EtOAc (100 mL)
5. washThe organic layer was washed with brine
6. dry with materialdried over MgSO4
7. concentrationconcentrated
8. dissolutionThe residue was dissolved in a mixture of THF/MeOH/H2O (20/20/10)
9. additionadded LiOH (61 mg)
10. stirringThe reaction was stirred overnight
11. concentrationconcentrated
12. additionThe aqueous residue was diluted with water
13. additionan HCl solution was added
14. filtrationThe resulting solid was filtered
15. washwashed with water
16. customdried