反应详情

A 250 mL cylindrical glass vessel equipped with a coarse glass frit was charged with 4-amino-N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-phenylalanine (10 g) obtained in Example 62 and a solution prepared from quinoline-4-carboxylic acid (5.2 g, 30 mmol), BOP (13.75 g, 30 mmol) and diisopropylethylamine (6.8 mL) in 70 mL of N-methylpyrrolidinone. The slurry was agitated for 4 hr. The mixture was filtered and washed with dichloromethane (2×100 mL), methanol (2×100 mL) and dimethylformamide (2×100 mL). To the washed resin was added a solution of 25% piperidine in N-methylpyrrolidinone (80 mL), the mixture was agitated at room temperature for 20 minutes and filtered. The process was repeated and the resulting slurry was filtered and washed with dichloromethane (2×100 mL), methanol (2×100 mL) and dimethylformamide (2×100 mL). Filtration afforded 4-[(4-quinolinylcarbonyl)amino]-L-phenylalanine on Wang resin suitable for use in the next step.

1. customA 250 mL cylindrical glass vessel equipped with a coarse glass frit
2. filtrationThe mixture was filtered
3. washwashed with dichloromethane (2×100 mL), methanol (2×100 mL) and dimethylformamide (2×100 mL)
4. additionTo the washed resin was added a solution of 25% piperidine in N-methylpyrrolidinone (80 mL)
5. stirringthe mixture was agitated at room temperature for 20 minutes
6. filtrationfiltered
7. filtrationthe resulting slurry was filtered
8. washwashed with dichloromethane (2×100 mL), methanol (2×100 mL) and dimethylformamide (2×100 mL)
9. filtrationFiltration