反应详情

To a stirred mixture of 2-((tert-butoxycarbonyl)amino)-2-methylpropanoic acid (180 mg, 0.89 mmol, 1.5 eq), triethylamine (209 mg, 2.07 mmol, 3.5 eq) and HOBt (120 mg, 0.89 mmol, 1.5 eq) in anhydrous CH2Cl2 (10 mL), EDCI (170 mg, 0.89 mmol, 1.5 eq) was added. The resulting mixture was stirred at RT for 30 min, and then 2-chloro-7-(piperazin-1-yl)-1,5-naphthyridine (D-19) (0.59 mmol, 1.0 eq) was added. The reaction mixture was stirred at RT for 20 h, and then quenched with water (30 mL) and CH2Cl2 (15 mL), and the organic layer was separated. The organic layer was washed with brine (10 mL), dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo. The resultant residue was purified by silica gel column chromatography (2% MeOH—CH2Cl2) to afford the desired product, tert-butyl(1-(4-(6-chloro-1,5-naphthyridin-3-yl)piperazin-1-yl)-2-methyl-1-oxopropan-2-yl)carbamate (D-20) (193 mg, 75.4% yield, 2 steps). ESI-MS m/z: 434.18[M+H]+.

1. additionwas added
2. stirringThe reaction mixture was stirred at RT for 20 h
3. customquenched with water (30 mL) and CH2Cl2 (15 mL)
4. customthe organic layer was separated
5. washThe organic layer was washed with brine (10 mL)
6. dry with materialdried over anhydrous Na2SO4
7. filtrationfiltered
8. concentrationThe filtrate was concentrated in vacuo
9. customThe resultant residue was purified by silica gel column chromatography (2% MeOH—CH2Cl2)