反应详情

温度

130 °C

A solution of methyl 2-(2-(((benzyloxy)carbonyl)amino)-2-methylpropanoyl)-5-oxo-1,2,3,4,5,10-hexahydrobenzo[b][1,7]naphthyridine-6-carboxylate (0.11 g) and hydrazine hydrate (1.0 mL) in DMA (1.5 mL) was heated at 130° C. for 1.5 h, acetic acid (2.0 mL) was added and the mixture was stirred at 130° C. for another 12 hours. The reaction mixture was cooled to room temperature, then water (15 mL) and EtOAc (50 mL) were added. The organic phase was separated and then washed with aqueous NaHCO3 (2×10 ml) and brine (20 ml), dried over Na2SO4, filtered, the organic phase was concentrated in vacuum to give the crude product, which was purified by Pre-HPLC to afford benzyl (2-methyl-1-oxo-1-(3-oxo-10,11-dihydro-2H-phthalazino[8,1-bc][1,7]naphthyridin-9(3H,7H,8H)-yl)propan-2-yl)carbamate (46 mg, 42%) as a yellow solid. 1H NMR (DMSO-d6) δ 11.8 (s, 1H), 10.6 (s, 1H), 8.4 (s, 1H), 7.65 (t, 1H, J=7.8 Hz), 7.49 (d, 1H, J=7.8 Hz), 7.25-7.35 (m, 6H), 4.90-4.91 (m, 2H), 4.34-4.40 (m, 2H), 3.83-3.89 (m 2H), 2.32-2.34 (m, 2H), and 1.40 (s, 6H). MS (ESI) m/e [M+1]+460.0.

1. temperatureThe reaction mixture was cooled to room temperature
2. customThe organic phase was separated
3. washwashed with aqueous NaHCO3 (2×10 ml) and brine (20 ml)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationthe organic phase was concentrated in vacuum
7. customto give the crude product, which
8. customwas purified by Pre-HPLC