反应详情

2-amino-5-bromo-pyridine-3-carboxylic acid (776.9 mg, 3.580 mmol) and triethylamine (724.5 mg, 997.9 μL 7.160 mmol) were added to a stirred solution of tert-butyl N-[[4-(hydrazinecarbonyl)phenyl]methyl]-N-methyl-carbamate (1 g, 3.580 mmol in DMF (8 mL). To the stirred slurry was added TBTU (1.724 g, 5.370 mmol) and the mixture stirred at ambient for 60 hours. The mixture was diluted with EtOAc/water and the layers separated. The mixture was extracted with ethyl acetate (×3) and the combined extracts washed with saturated aqueous NaHCO3 (×1) and brine (×1), dried (MgSO4), filtered and concentrated in vacuo. The resultant residue was purified by column chromatography (ISCO Companion™, 12 g column, 0-100% EtOAc/Petroleum ether) and the product containing fractions concentrated in vacuo. The residue was triturated from acetonitrile to give the desired sub-title product as a cream solid (992 mg, 58% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.39-1.45 (m, 9H), 2.80 (s, 3H), 4.45 (s, 2H), 7.28 (s, 2H), 7.35 (d, J=8.2 Hz, 2H), 7.90 (d, J=7.8 Hz, 2H), 8.20 (d, J=2.4 Hz, 1H), 8.24 (d, J=2.2 Hz, 1H), 10.50 (s, 1H) and 10.54 (s, 1H) ppm; MS (ES+) 480.2.

1. customthe layers separated
2. extractionThe mixture was extracted with ethyl acetate (×3)
3. washthe combined extracts washed with saturated aqueous NaHCO3 (×1) and brine (×1)
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe resultant residue was purified by column chromatography (ISCO Companion™, 12 g column, 0-100% EtOAc/Petroleum ether)
8. additionthe product containing fractions
9. concentrationconcentrated in vacuo
10. customThe residue was triturated from acetonitrile